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Chapter 11. Synthetic methods

 

作者: A. P. Davis,  

 

期刊: Annual Reports Section "B" (Organic Chemistry)  (RSC Available online 1984)
卷期: Volume 81, issue 1  

页码: 247-290

 

ISSN:0069-3030

 

年代: 1984

 

DOI:10.1039/OC9848100247

 

出版商: RSC

 

数据来源: RSC

 

摘要:

11 Synthetic Methods By A. P. DAVIS Department of Chemistry Trinity College Dublin 2 Ireland 1 Introduction This report is presented in almost exactly the same format as last year’s. A major division is made between methods for the construction or alteration of the carbon skeleton of a molecule and methods for the introduction and modification of functional groups. These sections are then systematically subdivided the former according to topology (connection of separate fragments cyclization etc.) and the latter into oxidations reductions and non-redox conversions. The coverage is intended to reflect the interests and concerns of those chemists who are involved in synthetic methodology in general as opposed to those who are concentrating on a particular area.Even with this limitation it has been necessary to exclude a great deal of material which was well-qualified for inclusion and it is probably vain to hope that the result will not appear biased to a large number of readers. 2 C-C Connection and Disconnection Connection of Separate Fragments.-Enolates and their Equivalents. The intensive investigation of enolate chemistry which has been pursued over the past few years shows no sign of abating. Significant advances in the regio- and stereo-selective formation of enolates have been made by two groups who have discovered conditions under which carbonyl compounds may be deprotonated and immediately trapped in situ. Thus the treatment of a range of ketones with potassium hydride in the presence of t-butyldimethylsilyl chloride gave enol silyl ethers derived from the more stable (‘thermodynamic’) enolate.Selectivity was improved by the addition of HMPA. In this way 2-enol ether (1) and its stereoisomer were formed from pentan-3-one in the ratio 97 :3.’ OSiMe, + ’ J. Orban T. Turner and B. Twitchin Tetrahedron Lett. 1984 25 5099. 247 248 A. P. Davis On the other hand it has been found that at -78 “Cin THF trimethylsilyl chloride can be used to trap ‘kinetic’ enolates generated from ketones and esters by lithium di-isopropylamide (LDA). The selectivity was invariably greater than that obtained via the usual two-step procedure. A further improvement was made by replacing the LDA with lithium t-octyl-t-butylamide a new highly hindered amide base.These conditions allowed the preparation from pentan-3-one of E-enol ether (2) and its stereoisomer in the ratio 98:2.’ QSiMe R4SiMe Reagents i CO(1 atm.) Et20 15 “C; ii Me3SiC1 Scheme 1 A new synthesis of acylsilane enolates is shown in Scheme 1. An a-lithiosilane adds to carbon monoxide to give an intermediate acyl-lithium which rearranges to give specificially the E-enolate (3).3 The ‘simple diastereosel’ectivity’ of the aldol reaction (the relative configurations of the two newly formed chiral centres) has most often been discussed in terms of the Zimmerman-Traxler ‘chair’ transition-states? The general tendencies predicted and observed are that 2-enolates give syn aldols while E-enolates give anti aldols. However in a few cases this rule is broken by enolates which give syn aldols irrespective of their geometry.Recently two groups have independently reported that enolborates react in this fa~hion.’.~ Thus enolborates (4) and (5) both react with benzaldehyde to give the syn aldol (6) after decomplexation with triethanolamine. In each case the diastereomeric excess (d.e.) was 90% or greater.’ E. J. Corey and A. Gross Tetrahedron Lett. 1984 25 495. S. Murai I. Ryu J. Iriguchi and N. Sonoda J. Am. Chem. SOC.,1984 106 2440. D. A. Evans Top. Stereochem 192 13 1. R. W. Hoffmann and K. Ditrich Tetrahedron Lett. 1984 25 1781. C. Gennari L. Colombo and G. Poli Tetrahedron Lett. 984 25 2279; C. Gennari S. Cardani L. Colombo and C. Scolastico Tetrahedron Lett. 1984 25 2283. Synthetic Met hods This result is all the more remarkable because E-enolboranes are particularly successful in anti-selective ald01s.~ The Mukaiyama addition of enol silanes to aldehydes catalysed by Lewis acids has been reported to give poor simple diastereoselectivity (a result confirmed recently in a systematic study by Heathcock7).However Reetz and co-workers have recently found that for Mukaiyama reactions with a-and /I-alkoxyaldehydes catalysed by TiC14 a good diastereofacial selectivity ('chelation-controlled') is accompanied by good simple diastereoselectivity. Thus the complex (7) reacted with enolsilane (8) to give virtually exclusively the diastereomer (9) (Scheme 2).* It was proposed that Ph' (7) (9) Scheme 2 the position of the Ti atom forced by chelation to co-ordinate anti to the aldehyde H was the crucial factor.This is supported by the fact that analogous BF,.Et,O- catalysed reactions show poor simple diastereoselectivity. The latter Lewis acid is incapable of chelation and is thought to form complexes such as (10) with a-alkoxyaldehydes. In accord with this (10) gives 'non-chelation-controlled'products of the form (11) with nucleophiles N such as enolsilanes.' Tetra-substituted enolates of defined stereochemistry are quite rare in acyclic systems. Scheme 3 shows how such a species may be formed from an unsaturated thioamide and how it may be used in a diastereoselective aldol condensation." The stereochemical control in the first step is presumably due to co-cordination of the thioamide sulphur atom to the magnesium in the Grignard reagent.Remarkable simple diastereoselectivity has been observed in Michael reactions of lithium ester enolates under certain conditions. Examples are given in Scheme 4 showing how variations in solvent and in the enolate ester group R lead to dramatically different stereochemical results.' 'C. H. Heathcock K. T. Hug and L. A. Flippin Tetrahedron Lett. 1984 25 5973. M. T. Reetz K. Kesseler and A. Jung Tetrahedron 1984 40,4327. M. T. Reetz and K. Kesseler J. Chem. Soc. Chem. Commun. 1984 1079. Y.Tamaru T. Hioki S.4. Kawamura H. Satomi and Z.4. Yoshida J. Am. Chem Soc. 1984 106,3876. 'I M. Yarnaguchi M. Tsukamoto S. Tanaka and 1. Hirao Tetrahedron Lett. 1984 25. 5661. 250 A. €? Davis Reagents i EtMgBr; ii EtCHO Scheme 3 I R 0.A \ /C=CHMe + %-I 1 + Y-7 LiO CO,Et RO2C CO,Et R02C C0,Et R = Et reagents i ;>20 1 R = Bu' reagents ii; 1 >20 Reagents i THF. HMPA -78 "C ii THF. -78 "C Scheme 4 Very high stereoselectivity has been reported for the alkylation of enolates sub- stituted in the /3 position by a dimethylphenylsilyl group. Scheme 5 shows how the P-silylester (12) (94% d.e.) could be formed in two steps from methyl cinnamate,12 then oxidized stereospecifically to the P-hydroxyester (13).13 For the alkylation of the intermediate enolate the authors suggest a transition state (14) in which the P-H eclipses the enolate C=C and attack by iodomethane occurs anti to the silicon. PhMezSi uoMe . .. I I1 iii,iv ---+ PhdOMe Ph UOMe Ph Reagents i.(PhMe,Si),CuLi; ii Mel; iii HBF, iv m-CPBA Scheme 5 There continue to be many reports concerning enolates containing removable chiral auxiliaries. A lot of attention has been paid to enolates derived from acyl iron complexes such as (15). For example Scheme 6 shows how (15) can undergo two highly diastereoselective C-C bond-forming reactions to give the erythro 12 W. Bernhard 1. Fleming and D. Waterson J. Chem. Soc. Chem. Commun. 1984 28. 13 . 1. Fleming R. Henning and H. Plaut J. Chem. Soc. Chem. Commun. 1984. 29. Synthetic Methods 25 1 P-hydroxyacid ( 17).14For the second of these steps the enolate (16) is thought to take up the conformation shown and to be alkylated from the face opposite to the bulky Ph3P ligand.Assuming that this sequence can be conveniently carried out with chiral starting material it amounts to an enantioselective synthesis of (17). /vi iv vii if’ Me w I ,HEtJ. Reagents i BuLi THF -78 “C; ii Et,AICl -40 “C 45 min.; iii EtCHO; iv work-up; v BuLi (2 equiv.); vi MeI; vii Br, H20 Scheme 6 Another ‘chiral acetate enolate’ is the ester enolate (18) which reacts with a variety of aldehydes to give hydroxyesters (19) in approximately 90% d.e. The chiral auxiliary is derived from R-mandelic acid; the S enantiomer is also a~ailab1e.l~ Enolates derived from the amides (20) can be alkylated16 or acylated” with extremely high diastereoselectivities (Scheme 7). For a range of R’ and R2 and with few exceptions the products (21) and (22) were formed with d.e.’s of 98% or better.As shown the acylation can be followed by a stereoselective reduction analogous to one reported earlier by the same group. A number of publications this year have demonstrated that a chiral alkoxy-group on a nucleophilic ,sp2-hybridized carbon atom can exert stereocontrol in carbonyl 14 S. G. Davies 1. M. Dordor and P. Warner J. Chem. Soc. Chem. Commun. 1984 956. Is M. Braun and R. Devant Tetrahedron Lett. 1984 25 5031. 16 Y. Kawanami Y. Ito T. Kitagawa Y. Taniguchi T. Katsuki and M. Yamaguchi Tetrahedron Lett. 1984 25 857. l7 Y. Ito T. Katsuki and M. Yamaguchi Tetrahedron Lett. 1984. 25. 6015. 252 A. P. Davis MOMO MOMO . .. I I1 111 L RZ R ' y0 -0MOM 0 0 MOMO I Reagents i LDA; ii R21;iii HCI aq.; iv BuLi; v R'COCI; vi Zn(BH,) Scheme 7 addition reactions.An example within enolate chemistry is the addition of the lithium enolate of alkoxyester (23) to acetone giving preferentially one diastereomer of ester (24) in 89% d.e.'* Further examples will be discussed in the section on ally1 anions (p. 254). The phase-transfer-catalysed alkylation of enolates presumably occurs tria quater-nary ammonium enolates. If a chiral ammonium ion is used it is possible that a chiral product may result. Early attempts at putting this into practice met with limited success but a recent report shows how careful optimization of a particular system can lead to satisfactory results. Thus N-benzylchinchonium chloride (25) catalysed the alkylation of indanone (26) with chloromethane to give (27) in up to 96% e.e.19 Two new reagents have been described which are unusual in that they will act as carbon electrophiles towards the a-carbons of ketones without requiring acid or base catalysis.The first is l,l,-bis(benzenesulphony1)ethene (28) which will react with neat butanone under reflux for example to give the ketone (29) quite regioselec- l8 J. d'hgelo 0. Pages J. Maddaluno F. Dumas and G. Revial Terrahedron Lett. 1984 25 5869. U.-H.Dolling P. Davis and E. Grabowski. J. Am. Chem. Soc.. 1984 106 446. Synthetic Methods (25) S0,Ph tively and in 75% yield.20 The second is the thiourea derivative (30),which efficiently carboxylates ketones in the a-position at room temperature in DMF.” Enol ethers may react as enolate equivalents albeit unreactive ones.Recently it has been shown that they can be alkylated not by the usual electrophilic reagents but by a free-radical reagent (e.g. Scheme 8).22 The reaction is performed by thermolysis of an a-hydroperoxydiazene such as (31) dissolved in the enol ether. The main limitation of the method may well be the highly explosive nature of the reagents. ,--Me + Me2C0 +N 52% Scheme 8 AZZyZ Anions and their Equivalents. As for the aldol reaction the questions of simple diastereoselectivity and diastereofacial selectivity are of particular concern in the reactions of ally1 organometallics with carbonyl compounds. Keck and co-workers 2o 0.de Lucchi L. Pasquato and G.Modena Tetrahedron Letr. 1984 25 3647. 21 N. Matsumura N. Asai and S. Yoneda J. Chem. Soc. Chem. Commun. 1984 1487. 22 E. Y. Osei-Twun D. McCallion A. S. Nazran R. Panicucci P. A. Risbood and J. Warkentin J. Org. Chem. 1984.49 336. 254 A. P. Davis have embraced both issues in a systematic study of the Lewis acid catalysed reactions of allyl- and crotyl-stannanes with aldehydes of the form (32) and (33).23With CH2CI2 as solvent they found that a combination of R = PhCH2 and a chelating Lewis acid (MgBr, SnCI etc.) maximized ‘chelation control’ to give (34)and (35) respectively (R’= CH2CH=CH or CHMeCH=CH,). The opposite diastereofacial selectivity (‘Felkin-Anh’ or ‘non-chelation’ control) was maximal with R = SiMe,Bu‘ and BF3.Et20 as the Lewis acid.Good simple diastereoselec- tivity could also be obtained; thus treatment of (32; R = PhCH,) with crotyltributylstannane and MgBr gave (36)in 85% d.e. Me IH 4e OR OH OH (35) (36) It has been reported by two groups that the tetrahydropyranyl group in allylboron- ates such as (38)can direct the stereochemistry of the two new chiral centres formed on additions to aldehydes.24v25 Scheme 9 shows how this was employed in an enantioselective synthesis of ( -)-exo-brevicomin (40).,’ The allyl tetrahydro- pyranyl ether (37)used as starting material was derived from dihydrocarvone. Out of 3 diastereomers formed in the aldehyde addition the desired compound (39) comprised 89% of the total. It is notable that this selectivity is paralleled in the enolate addition discussed earlier (p.252). Hoppe and his group have previously shown that aluminium derivatives of E-2-butenyl carbamates will add to aldehydes giving anti stereochemistry about the new C-C bond. They have now shown that the 2-analogue (41) will give the corresponding syn diastereomers [e.g. (42)in Scheme In both stereochemical series an interaction between the aluminium and the carbamoyl oxygen is thought to control the regiochemistry of the addition. The addition product (42) can be hydrolysed to the y-lactol derivative (43) so that the reaction is effectively a ‘homo-aldol’ reaction. Hoppe has published a review of this class of reaction^.^' 23 G. E. Keck and E. Boden Tetrahedron Lett 1984 25 265; G. E. Keck and E.Boden Tetrahedron Lett 1984 25 1879; G. E. Keck and D. E. Abbott Tetrahedron Lett. 25 1883. 24 R. Metternich and R. W. Hoffmann Tetrahedron Lett. 1984 25 4095. 25 P. Wuts and S. Bigelow J. Chem. SOC.,Chem. Commun. 1984 736. 26 D. Hoppe and F. Lichtenberg Angew. Chem. Int. Ed. Engl. 1984 23 239. 27 a.Hoppe Angew. Chem.. In?. Ed. Engl. 1984 23 932. Synthetic Methods \ (40) Reagents i Bu'Li; ii ;iv H,/Pd; v H30+ Scheme 9 (42) (d.e.80%) Reagents i BuLi pentane TMEDA -78°C; ii Bu;AIOSO2Me; iii MeCHO; iv AcOH; v MeOH MeS03H Hg(OAc) Scheme 10 An enantioselective homo-aldol reaction has been described employing the allyltitanium (44) as a reagent. With aldehydes RCHO adducts (45) are formed with ca. 90% d.e.28 H.Roder G. Helmchen E.-M. Peters K. Peters and H. von Schnering Angew. Chem. Int. Ed. Engl. 1984 23 898. 256 A. P. Davis According to a report by Yamamoto et al. ally1 organometallics can add to imines to give homoallylic amines. An interesting feature of the reaction is the remarkably high diastereofacial selectivity shown. Thus 9-allyl-9-borabicyclononanereacts with the irnine (46) to give exclusively the amine (47) as predicted by Cram's rule.29 The corresponding reaction of 2-phenylpropanal is only slightly stereoselective. The results can be rationalized with reference to the transition state (48). The trans configuration of the imine forces the chiral centre into an axial position where it will interact strongly with the alkyl substituents on the boron.In the case of the aldehyde there is nothing to prevent the chiral carbon occupying an equatorial position in the corresponding transition state. Me Me 1 A versatile synthesis of 2,E-dienes based on an allyltitanium species is shown in Scheme 11. In the resulting mixture of dienes the isomer (49)generally formed 95% of the total.30 R' SiMe,\MBu' S 1.. II.. Bu'S ?SiMe iii Ti(OPr'), I/ iv I Reagents i Bu'Li pentane THF; ii Ti(OPr'),; iii R'CHO; iv R'Mgl Ni" catalyst Scheme 11 29 Y. Yamarnoto T. Kornatsu and K. Maruyama J. Am. Chem. SOC.,1984 106 5031. 30 J. Ukai. Y. Ikeda N. Ikeda. and H. Yarnamoto. TefruhedronLeu. 1984 25. 5173. Synthetic Methods 257 Allyboronates feature reguarly as allyl anion equivalents (see above for examples).They may be synthesized stereoselectivity by a simple new procedure based on the reaction of vinyl-lithium reagents with the chloromethylboronate (50).31Finally it has been shown that the allyl anions derived from alkenes (51) can be alkylated specifically a to the stabilizing substituents. Scheme 12 shows how this can be utilized in a synthesis of a$-unsaturated ketones.32 (51) Ts = Me em,-Reagents i TsCH2NC KOBU'; ii POCI, Et3N; iii KOBU'; iv R3X (X = C1 Br I); v H30+ Scheme 12 Miscellaneous. The importance of diastereofacial selectivity in carbonyl addition reactions is not restricted to enolates and allyl anions of course. Reetz has reviewed the operation of chelation and non-chelation control in a range of additions to a-and P-alkoxycarbonyl compounds.33 A further type of nucleophile for which simple diastereoselectivity is conceivable is an allenyl organometallic.Reagents of this type have indeed been shown to add highly stereoselectively to both aldehydes and aldimines. Thus allenylzincs (52) added to aldehydes giving alcohols (53) in around 90% d.e. (Scheme 13).34 The selectivity is readily explained by invoking the transition state (54) ;analogous attack on the other face of the aldehyde would involve steric interference between R' and R2. A variety of reagents (55) were similarly successful in additions to aldimine~.~' R' (52) (53) Reagents i Bu'Li THF,-90°C; ii ZnC1,; iii R'CHO; iv H30+ Scheme 13 31 P. Wuts P. Thompson and G. Callen J. Org. Chem.1984 49 5398. 32 J. Moskal and A. van Leusen Tetrahedron Lerr. 1984 25 2585. 33 M. T. Reetz Angew. Chem. Int. Ed. Engi. 1984 23 556. 34 G. Zweifel and G. Hahn J. Org. Chem. 1984 49 4565. 35 Y. Yamamoto W. Ito and K. Maruyama J. Chem. SOC.,Chem. Commun. 1984 1004. 258 A. P. Davis Zn I.+SiMe3 M A great deal of interest was shown this year in synthons behaving effectively as (56). For example the silylated amine (57) was investigated by two groups,36 and shown to alkylate Grignard reagents organolithiums and silyl ketene acetals with loss of the methoxy-group. Also a review was published on ‘a-amidoalkylation’ synthons (58).3’ A complementary survey dealt with a-metalloamine synthetic equivalents (59).38 \/ I \“ N -4 M Several papers have appeared on the use of a-metallated organosilicon compounds as equivalents of a-metallated alcohols.39 This has been made possible by the recent discovery that an organosilicon compound with at least one acid-labile group can be oxidatively decomposed so that RSi is replaced by ROH.Another application was discussed A versatile ‘vinylene dication’ equivalent has been reported by Rosenblum.4’ The complex (60) will react with a variety of carbon nucleophiles to give adducts from which ethanol can be eliminated stereospecifically. The result is a displacement of ethoxide by the nucleophile with net inversion giving a trans alkenyl complex e.g. (61) in Scheme 14. Repetition of the sequence with a second nucleophile followed by decomplexation gives a cis alkene such as (63).Usefully the trans complexes such as (61) are usually less stable than their cis analogues; thus thermal isomeriza- tion of (61) gives (62),which can be transformed ultimately to the trans alkene (64). There have been some interesting developments in the area of carbonyl olefination. One long-standing problem has been the lack of stereoselectivity in Wittig olefinations with ylids Ph,=CHR where R = aryl or alkenyl. Recently it was reported that replacement of one of the phenyl groups on phosphorus improved matters considerably (e.g. Scheme 15).41 The best E-selectivity was generally achieved using ‘salt-free’ conditions. 36 H. J. Bestmann and C. Wolfel Angew. Chem. Int. Ed. Engl. 1984,23 53; T. Morimoto T. Takahashi and M.Sekiya J. Chem. Soc. Chem. Commun. 1984 794; K. Okano T. Morimoto and M. Sekiya J. Chem. SOC.,Chem. Commun. 1984 883. 37 H. Zaugg Synthesis 1984 85 and 181. 38 P.Beak W. Zajdel and D. Reitz Chem. Rev. 1984 84 471. 39 K. Tamao T. Iwahara R. Kanatani and M. Kumada Tetrahedron Lett. 1984,25 1909; K. Tamao and N. Ishida Tetrahedron Lett. 1984 25 4245; ibid. 4259. 40 M. Marsi and M. Rosenblum J. Am. Chem SOC 1984 106,1264. 41 E. Vedejs and H. W. Fang J. Org. Chem. 1984,49 210. Synthetic Methods (61) (62) Fp = q5-C,H,Fe(CO) (63) 52% (64) 38% Reagents i Me2CuLi THF -78 "C; ii HBF4.Et,0 -78 "C; iii r.t. 30 min.; iv -78 "C; v Nal Me2C0 25 "C Scheme 14 R = Ph; 1:l R = crotyl; 14:l Reagents i BuLi; ii Scheme 15 The anion derived from the chiral phosphonamide (65) was found to olefinate 4-t-butylcyclohexanone to give one enantiomer of the product alkene in 90% e.e?2 It has been discovered that the organomolybdenum reagents (66) and (67) can be used in the presence of water and ethanol.43 The Peterson olefination has been reviewed.44 Me 42 S.Hanessian D. Delorme S. Beaudoin and Y.Leblanc J. Am. Chem. SOC 1984 106 5754. 43 T.Kauffmann P. Fiegenbaum and R. Wieschollek Angew. Chem. Int. Ed. En& 1984 23 531. 44 D. J. Ager Synthesis 1984 384. 260 A. P. Davis Many of the most powerful and versatile stereospecific olefin syntheses rely on additions to acetylenes. A valuable new development is exemplified in Scheme 16.45 The first step carbotitanation of an alkynylsilane was known previously but stereospecific oxidative cleavage to give halogeno-alkenes such as (68) had not been achieved before.The products should serve as intermediates in the stereoselective synthesis of tetra-substituted olefins. Reagents i Et,AICI CpzTiC12 CH,Cl2 6 h 25 "C; ii N-iodosuccinimide CH,CI, 2 h -78 "C Scheme 16 Vinyl halides are often useful intermediates in olefin synthesis particularly in transition-metal-catalysed coupling reactions. It has recently been shown that vinyl trifluoromethanesulphonates (vinyl triflates) (69) can substitute for the halides in certain of these reactions. Thus the triflates which are readily available from ketones alkenylated alkenes (70) to give dienes (71) under palladium catalysis (Scheme 17).46 The reaction was most efficient with cyclic triflates derived from steroids.Alkenes containing no electron-withdrawing group could also be alkenylated but the reactions were not generally regioselective. -"+O,f+ R3 i R1-)qo R' R3 (69) (70) (71) Tf = CF3S02 Reagents Et3N Pd(OAc)z Ph3P Scheme 17 A more versatile (but more elaborate) relative of the above reaction involved coupling of the triflates with a variety of stannanes R3SnR3 (R3=alkenyl allyl alkynyl alkyl or H) giving alkenes (72):' It was also shown that carbon monoxide 4s R. Miller and M. Al-Hassan J. Org. Chem 1984 49 725. 46 S. Cacchi E. Morera and G. Ortar Tetrahedron Lett. 1984 25 2271. 47 W.Scott G. Crisp and J. K. Stille J. Am.Chem. Soc.. 1984 106 4630. Synthetic Methods 26 1 could be incorporated in the products of this type of reaction (Scheme 18). This was demonstrated both for X = I R3 = alkenyl alkynyl ary1,48 and for X = OTf R3 = alkenyl allyl alkynyl alkyl a1yl.4~ The yields were generally good and it is notable that pressures of only 1-3 atmospheres of CO were required. Reagents i Pd" catalyst (2 mol. O/O) CO (1-3 atm.) THF; ii Pd(PPh,) (3 mol. O/O) CO (1-3 atm.) THF Scheme 18 Several other transition-metal-catalysed carbonylations have been reported. One example is the reaction of halides R'Br with borates B(OR2) and carbon monoxide to give esters R'C02R2. When [hexa-1,5-diene RhC1I2 was used as catalyst the reaction was useful only for benzylic halides but the addition of Pd(PPh3)4 to the system broadened the scope considerably so that good yields were obtained for R' = alkyl vinyl and aryL5' Scheme 19shows an example of another useful carbony- lation.An important advantage of this reaction is that the conditions are compatible with a variety of functional groups. Ring-opening occurs selectively at the primary carbon of the epoxide but will also occur at a secondary centre if there is no choice. In such cases inversion of configuration is observed." i MeO-OSiEt ,Me Meopo -0 OSiEtzMe Reagents i HSiEt2Me CO~(CO)~ cat. CO (1 atm.) CH2Cl2 25 "C Scheme 19 Evidence is emerging that a variety of organometallic reagents can be used in the presence of Lewis acids which considerably moderate their reactivity.A particularly useful combination appears to be that of BF3.Et20 with an organocopper reagent. Thus it has recently been reported that R2CuLi/BF3*Et20 reacts rapidly and cleanly with epoxides acetals and or tho ester^.^^ The reaction with acetals does not occur at all in the absence of BF, and is perhaps particularly useful because chirality may be transferred from the acetal moiety to the new asymmetric centre formed (e.g. Scheme 20). The same reagent has also been found to add quite cleanly to imines a reaction which is complicated by side reactions for most other organometal- lic reagents.53 BF3 may also be used to increase the potency of 'higher-order' cuprates. For example Ph,Cu(CN)Li will react with isophorone (73) to give adduct (74) in the presence of BF3-Et20.Without the Lewis acid no adduct is formed.54 48 W. Goure M. Wright P.Davis S. Labadie and J. K. Stille X Am. Chem. SOC. 1984 106 6417. 49 G. Crisp W. Scott and J. K. Stille J. Am. Chem. SOC.,1984 106 7500. 50 K. Hashem J. Woell and H. Alper Tetrahedron Lett. 1984 25 4879. " T. Murai S. Kato S. Murai T. Toki S. Suzuki and N. Sonoda J. Am. Chem. Soc. 1984 106 6093. 52 A. Ghribi A. Alexakis and J. F. Normant Tetrahedron Lett. 1984 25 3075 and 3083. 53 M. Wada Y. Sakuri and K.-y. Akiba Tetrahedron Lett. 1984 25 1079. 54 B. Lipshutz D. Parker J. Kozlowski and S. Nguyen Tetrahedron Lett. 1984 25 5959. 262 A. P. Davis 100°/~d.e. Reagents i Me2CuLi BF,.Et,O Et20 -78 "C to -50 "C Scheme 20 Remarkably it appears that even the highly reactive organolithium reagents can be used with BF3 at low temperatures.An example is shown in Scheme 21. Without the BF, the organolithium desilylated (75) in preference to opening the epoxide. A number of control experiments suggested strongly that the organolithium and the Lewis acid were acting separately within the reaction mixture.55 (75) Li Reagents i EtO < BF,.0Et2 THF -78 "C Scheme 21 Organometallic reagents derived from Lewis acidic metals might be expected to show quite similar reactivity to the systems discussed above. Indeed it has been shown that MeTiC1 will react with acetal (76) to give (77) in 88% d.e. (cJ Scheme 20). It is notable that this reagent is virtually unreactive towards nonan-5-one under the same condition^.'^ (76) (77) 55 M.Eis J. Wrobel and B. Ganem J. Am. Chem. SOC.,1984 106 3693. 56 A. Mori K. Maruoka and H. Yamamoto Tetrahedron Lett.. 1984. 25. 4421. Synthetic Methods There has been a quite intensive search for organocuprates RCuXLi which will efficiently transfer the alkyl group R without wastage. Recently it has been suggested that the ligand X of choice should be dicyclohexylphosphide and that LiBr should be present in the reaction mixture for maximum effecti~eness.~’ The use of Cu’ compounds as catalysts in the reactions of organolithiums and Grignard reagents has been reviewed.58 It is likely that the highly reactive sodium and potassium organometallics could be useful in carbon-carbon bond formation if they were not insoluble in the few solvents to which they are stable.It has now been reported that phenylsodium and phenylpotassium can be solubilized in benzene by Mg(OCH2CH,0Et),. The solu- tions are shelf-stable at 20°C or below and behave as expected for organo- alkali-metal reagents (i.e. the phenyl group is apparently not transferred to the magne~iurn).~~ Finally the following reviews contain material pertinent to this section; ‘Car- bometallation; addition of organometallic compounds to isolated multiple bonds in functionally substituted compounds’,60 ‘Carbene complexes in organic syn- thesis*,6’ ‘Three-carbon homologating agents*,62 ‘Organo-iron complexes of aromatic compounds-applications in ~ynthesis’,~~ ‘Palladium(1 ])-assisted reactions of mono- olefin~’,~~ and ‘Copper-assisted nucleophilic substitution of aryl halogen’.65 Cyclization.-Two new cyclization reactions show familiar functional groups behav- ing in rather unusual ways.The first is exemplified in Scheme 22.66 It is well- established that a sulphonyl group attached to an sp3-hybridized carbon atom will stabilize a negative charge on the carbon allowing it to react with an electrophile. However it is unusual for the sulphonyl to act as a leaving group allowing the carbon atom to react with a nucleophile. Last year a rearrangement was reported in which a sulphonyl group was induced to leave by a Lewis acid and Scheme 22 shows how the same principle has recently been employed in a cyclization. This development allows sulphones to be considered potentially as ‘1-1 dipoles’ R‘R’c+-.Reagents i AICI, ether Scheme 22 57 S. Bertz and G. Dabbagh J. Org. Chem. 1984.49 1 119. 58 E. Erdik Tetrahedron 1984 40,641. 59 C. Screttas and M. Micha-Screttas Organometallics 1984 3 904. 60 J. Vara Prasad and C. Pillai J. Organomef.Chem. 1983 259 1. 61 K. Dotz Angew. Chem. Inf. Ed. Engl. 1984 23 587. 62 J. Stowel Chem. Rev. 1984 84 409. 63 D. Astruc Tetrahedron 1983 39 4027. 64 L. S. Hegedus Tetrahedron 1984 40,2415. 65 J. Lindley Tefrahedron,1984 40 1433. 66 B. Trost and M. Ghadiri J. Am. Chem. Soc. 1984 106 7260. 264 A. P. Davis Similarly while a trimethylsilyl group is known in many circumstances to act as an electrofugal leaving group and thus a source of nucleophilic carbon it is not generally perceived to be of use if it is remote from any other functionality.The cyclization shown in Scheme 23 proves that this need not be the case.67 The example chosen demonstrates that the conditions required are not so vigorous as to preclude the presence of other functional groups. Reagents i LDA HMPA THF; ii J.,+,-SiMe.3 ; iii (COCI), C6H6; iv AICI, CH,CI Scheme 23 Another new cyclopentanone synthesis is the rhodium-catalysed cyclization of 3,4-disubstituted enals such as (78) to give cis-disubstituted products in good yields (Scheme 24). Again an example has been chosen to demonstrate that a high degree of functionality can be tolerated. The reaction is a development of earlier work which showed that analogous 2,3-disubstituted enals gave much poorer results.The authors postulate that the stereoselectivity arises from intramolecular H-transfer within an intermediate (79) in which steric interactions between R' and R2 are minimized.68 0 0 .c1 Reagents i (Ph,P),RhCI CH2C12,r.t. 4 h Scheme 24 H (79) 67 H. Urabe and I. Kuwajima 1. Org. Chem. 1984 49 1140. 68 K. Sakai Y.Ishiguro K. Funakoshi K. Ueno and H. Suemune Tetrahedron Lett. 1984. 25,961 Synthetic Methods 265 A convenient synthesis of cyclopentanones is the cyclization of enynes (80) with PdCl,(MeCN)2 as catalyst. The products (81) were shown to arise uia cyclopen-tadienes (82) by trapping experiments using the powerful dienophile N-phenyl- maleimide.69 0 OAc Scheme 25 shows a new synthesis of 1,2-bisalkylidenecyclohexanes(83) clearly of potential use in the construction of polycyclic compounds.The E,E isomers were formed selectively. Analogous cyclizations to give 5-and 7-membered rings were also successfu~.~~ R' =-. @ R' i,ii 4 -R2 (83) Reagents i Cp,TiC12 Ph2PMe Na-Hg THF; ii H30+ Scheme 25 Although benzenoid aromatics are more usually synthesized by substitution reac- tions a route involving the cyclization of an acyclic precursor may in many cases be more efficient. The latter approach is surveyed in a recent review.71 Cycloadditions and Annu1ations.-Diels- Alder Reactions. Interest continues in Diels- Alder reactions of dienophiles with removable chiral auxiliaries.Among recent publications in the area are a review by Oppol~er,'~ and reports on the highly stereoselective Lewis acid-catalysed Diels-Alder reactions of (84),73 (85),73 and (86).74The first two give complementary product stereochemistries while the latter 00 00 RdNAO RdNAO &NL L-J / R Me Ph (84)(R = H,Me) (85) (R = H Me) (86)(R = H,Me) 69 V. Rautenstrauch J. Org. Chem. 1984 49 950. 70 W. Nugent and J. Calabrese J. Am. Chem. SOC.,1984 106 6422. 71 P. Bamfield and P. F. Gordon. Chem. SOC.Rev.. 1984 13. 441. 72 W. Oppolzer Angew. Chem. ini. Ed. Engl. 1984 23 876. 73 D. A. Evans K. Chapman and J. Bisaha J. Am. Chem. SOC.,1984 106 4261. 74 W. Oppolzer C. Chapuis and G. Bernardinelli Helv. Chim. Acfa 1984 67 1397.266 A. P. Davis is available in both enantiomers. These dienophiles are all notable for their crystal- linity and high reactivity; in many earlier procedures the chiral auxiliary could only be used with an acryloyl moiety and not with the less reactive crotonyl group. Sustained interest has also been shown in the development of dienophiles which will act as 'acetylene-equivalents' in Diels-Alder reactions. In the past year a review has appeared,75 as well as a new solution to the problem which is represented in Scheme 26.76 In the example shown the key electrolytic elimination step occurred in 83% yield. Reagents i 60 "C 18 h ii hydrolysis iii electrolysis in MeCN-EtOH-KOH Scheme 26 It has been reported that Diels-Alder reactions can be induced to occur under very mild conditions when catalysed by K10 montmorillonite clay doped with Fe3+ or A13+.For example the adduct between furan and acrolein was formed in 65% yield after 15 minutes at -43 0C.77Previously this addition had been successfully accomplished only at very high pressures. It is possible that Lewis acidic centres and 'pools' of water within the clay may jointly be responsible for the catalysis. In reactions between cyclopentadiene and butenone employing a variety of solvents stereoselectivities were observed which were very similar to those obtained earlier in aqueous solution.78 Two comprehensive reviews have appeared on the intramolecular Diels- Alder reaction.79 Other Reactions Forming 6-Membered Rings. The cyclocondensation of 1,3-dioxyge- nated dienes with carbonyl compounds has received further investigation.It has been reported that whereas the diene (87) reacted with simple aldehydes to give the cis-disubstituted dihydropyrones (88) alkoxyaldehyde (90) reacted to give the trans isomer. Furthermore only one face of the aldehyde was attacked resulting in control'of the relative stereochemistry in all three asymmetric centres of the product (89) (Scheme 27).*' These results were rationalized by reference to transition states (91) and (92). In the former the metal and its ligand sphere are co-ordinated anti to R in the aldehyde and are supposed to be sterically dominant. In the latter chelation to the a-alkoxy substituent in the aldehyde holds the metal syn to the bulk of the aldehyde.Chelation control also appeared to be effective in the Eu"'-catalysed reaction of diene (93) with a-alkoxyhexanals. Again the products (94) had the threo 75 0.De Lucchi and G. Modena Tetrahedron 1984 40 2585. 76 D. Hermeling and H. Schafer Angew. Chem. Int. Ed. EngL 1984 23 233. 77 P. Laszlo and J. Lucchetti Tetrahedron Lett. 1984 25 4387. P. Laszlo and J. Lucchetti Tetrahedron Lett. 1984 25 2147. 79 E. Ciganek Org. React. 1984 32 1; A. G. Fallis Can. J. Chem. 1984 62 183. 8o S. Danishefsky W. Pearson and D. Harvey. J. Am. Chem. SOC.,1984 106 2456. Synthetic Methods OMe < iii ii , 2 Me Me-;.:”R OCH2Ph 0 Me3Si0 Me Me Me Et (88) (87) (89) Reagents i RCHO Lewis Acid; ii AcOH; iii E:(90) MgBr, THF Et Scheme 27 Me OMe H Et (92) 0 OSiMe FOMe Me0 HI Me0& Bu (93) (94) stereochemistry.This diene is unusual in that it is reactive enough to undergo cyclocondensation with ketones as well as aldehydes.81 Until recently nitrosoalkenes have appeared to be of only limited use as ‘heterodienes’. However a new study has appeared in which these reactive intermedi- ates were successfully trapped in a stereoselective intramolecular [4 + 21 cycloaddi-tion (Scheme 28). The most successful reaction conditions were those which gave very slow generation of the nitrosoalkene.82 Reagents i CsF MeCN 20 h (for R = Me); KF MeCN 336 h (for R = H) Scheme 28 81 M. Midland and R. Graham J. Am.Chem. SOC.,1984 106 4294. 82 S.Denmark M. Dappen and J. Sternberg J. Org. Chem. 1984 49 4741. 268 A. P. Davis A highly versatile new heteroannulation method is illustrated in Scheme 29.83As shown the sequence allows the addition of a C2X or a C3X component to one double bond of a conjugated diene or vinylcyclopropane; an example was also reported of a [3 + 31 annulation involving a 1,4-diene and a C2X unit. In general the first step proceeds via transmetallation of the mercurial to give an organopal- ladium species which then adds to the olefinic component to give a (?r-allyl) palladium intermediate (e.g. Scheme 30). In the second step the palladium is displaced by intramolecular nucleophilic attack of the heteroatom X. c140zH HgCl + 0-c1 p O H Me c1’ Reagents i LiPdCI,; ii K,CO,; iii NaH Scheme 29 PdCl XH __* + LiPdCI3 + 0-& 0 base Scheme 30 An annulation reaction in which an alkene is converted into a cyclohexadienone is shown in Scheme 31.This conversion is an extension of earlier benzannulation reactions which were analogous except in that the final products could tautomerize to phenols. The addition is regioselective with the substituent on the acetylene ending up (Y to the carbonyl and is also quite stereoselective; for R = Bu the product (95) was formed in 80% d.e.84 83 R. C. Larock L. Harrison and M. Hsu 1. Org. Chem. 1984 49 3662. 84 P.-C. Tang and W. Wulff 1. Am. Chem. SOC.,1984 106 1132. Synthetic Methods -+ R-=-H Me Me OMe Reagents i THF 45 "C 24 h; ii air (95) Scheme 31 The last ten years have seen sustained development in the application of cobalt- catalysed [2 + 2 + 23 cycloaddition reactions to organic synthesis.Most of this has been due to Vollhardt and he has recently published a review of the area.85 Other Ring Sizes. An area which has been widely researched over the past decade is the addition of a three-carbon unit to two adjacent carbon atoms to create a new cyclopentane ring. Such 'cyclopenta-annellation' reactions have been reviewed sys- tematically,86 and two new examples of interest have been reported. (99) (98) Reagents i THF catalyst from Pd,(dba),CHC13 + dppe Scheme 32 Firstly ally1 carbonates (96) (El = Ts or CN) were found to react with electron- deficient alkenes (97) (E2 = COR or C02R) under Pdo catalysis to give cyclopen- tanoids (Scheme 32).For E' = Ts the reaction stopped at the methylenecyclopen- tanes (98) but for E' = CN these initial products generally isomerized to the cyclopentenes (99).87 Secondly highly electron-deficient olefins such as (100)reacted thermally with cyclopropene (101) to give cycloadducts such as (103) (Scheme 33). This reaction is unusual in being a single-step cyclopenta-annellation requiring no transition-metal catalysis. It was presumed to occur via dipolar intermediates such as (102)." 85 K. P. C. Vollhardt Angew. Chem. Int. Ed. Engf. 1984 23 539. 86 M. Ramaiah Synthesis 1984 529. 87 I. Shimizu Y. Ohashi and J. Tsuji Tetrahedron Lett. 1984 25 5183. 88 D. Boger and C.Brotherton J. Am. Chem. Soc. 1984 106 805. 270 A. P. Davis n EtO,C + EtOZC&' Me Me 57% Reagent i C6H6 75 "c 15 h Scheme 33 A few years ago Marino reported that dichloroketene reacted with 1-alkenyl sulphoxides to give y-butyrolactones. He has now published a study of the same synthesis with single enantiomers of the sulphoxides and has found that the stereochemical information is transferred completely from the sulphur to the new bonds in the product. Furthermore it has been shown that the reaction can be extended to monochloroketene and that the extra asymmetric centre in the resulting products is also formed in one sense only. Thus optically pure (104) was converted to optically pure (105) in a reaction which generated three new chiral centres stereospecifically (Scheme 34).89 Reagents i HCCl,COCI Zn Et,O Scheme 34 Although ketenes do not readily cycloadd to simple alkynes it has been known for some time that tetramethylketeniminium salts (106) (R' R2 = Me) will do so successfully.The reaction has now been extended to the less-substituted examples having R' R2 = H Me and R' R2 = H.90The salts can be obtained by dehydration of amides (107) with trifluoromethanesulphonic anhydride and collidine. The cyclo- butenones resulting from the cycloadditions (followed by aqueous work up) undergo a number of useful further transformations. 89 J. P. Marino and A. Perez 1.Am. Chem. SOC.,1984 106 7643. 90 C. Schmidt S. Sahraoui-Taleb E. Differding C. Dehasse-De Lombaert and L.Ghosez Tetrahedron Lett. 1984 25 5043. Synthetic Methods 27 1 The cycloaddition of allyl cations to 1,3-dienes has been developed into a useful synthesis of 7-membered carbocyclic rings. The area has been reviewed by Hoffmann.” Rearrangements-A number of noteworthy publications concerned the Claisen rear- rangement. In general the widely used modifications of this reaction give products at the carboxylic acid oxidation level. In order to obtain aldehydes directly it is necessary to start with allyl vinyl ethers and the syntheses of such compounds can be problematical. Scheme 35 outlines a new modification which gives acceptable yields and appears to be quite ~onvenient.~~ The reagent (108) is obtained from trimethylamine and ethyl propiolate.‘R3 1 R2 Reagents i (108); ii H,O+;iii 150-200 “C hydroquinone (trace) Scheme 35 The stereochemical influence of neighbouring hydroxyl or alkoxyl groups in the Claisen ester-enolate rearrangement has been in~estigated.9~ In one example rear- rangement of the silyl ketene acetal derived from (109) led predominantly to the diastereomer (110). The other three diastereomers comprised only ca. 10% of the mixture. OMe Reviews have appeared on catalysis of the Cope and Claisen rearrangement^,^^ and on mercury(r1)- and palladium(I1)-catalysed [3,3]-sigmatropic rearrangement^.^^ As a further development in the exploration of the Wittig [2,3]-rearrangement as a stereoselective synthetic method attention has been directed towards the enantiospecificity of the reaction.In particular two groups have observed that 91 H. M. R. Hoffmann Angew. Chem Int. Ed. EngL 1984,23 1. 92 G. Buchi and D. Vogel J. Org. Chem. 1983,48 5406. 93 J. Cha and S. Lewis Tetrahedron Left. 1984,25,5263 ;M.Kurth and C.-M. Yu Tetrahedron Lett. 1984 25 5003. 94 R. P.Lutz Chem. Rev. 1984,84 205. 95 L. E. Overman Angew. Chem. Inr. Ed. Engl. 1984 23 579. 272 A. P. Davis 07Me Me * ""r*, HO' SiMe3 SiMe3 optically enriched ally1 propargyl ethers (111) give alcohols (1 12) with virtually complete stereospecificity on rearrangement with butyl-lithi~m.~~ The thermal rearrangement of isonitriles to nitriles has attracted considerable theoretical interest for many years but because it has been difficult to perform cleanly it has not proved to be of great use in synthesis.Now largely as a result of the mechanistic studies it has been discovered that under conditions of flash vacuum pyrolysis ( Torr ca. 500 "C) the reaction occurs cleanly in excellent yield and with retention of configuration in the migrating group. In suitable cases the conver- sion R*NH2 to R*C02H is thus now po~sible.~' 0 Bu i ii iii Me Ph ___. OH Bu Reagents i Bu-E-Li THF -78 "C; ii LiAIH4 THF; iii pyH+TsO- EtOH; iv MsCI Et,N CH2CI2 0"C;v Et3AI hexane -42 "C Scheme 36 Pinacol-type rearrangements in acyclic systems generally suffer from a lack of stereospecificity due to the involvement of carbonium ion intermediates. Recently mild conditions have been found which allow the stereospecific migration of alkenyl and aryl groups in mesylates.One example is shown in Scheme 36.98 The chiral ketone (113) used as a starting point was made from a lactic acid derivative. Not only is there complete inversion of configuration at the migration terminus but also the migrating alkenyl group retains its configuration. A similar rearrangement is observed on reduction of ketones (114) (R = aryl alkenyl) with di-isobutyl- aluminium hydride leading to aldehydes which are further reduced to primary alcohols (115).99 96 D. Tsai and M. Midland J. Org. Chem. 1984 49 1842; N. Sayo K.4. Azuma K. Mikami and T. Nakai Tetrahedron Lett. 1984 25 565. 97 M. Meier and C. Ruchardt Tetrahedron Lett. 1984 25 3441.98 K. Suzuki E. Katayama and G.-i. Tsuchihashi Tetrahedron Lett. 1984 25 1817. 99 K. Suzuki E. Katayama T. Matsumoto and G.4. Tsuchihashi Tetrahedron Lett. 1984 25 3715. Synthetic Methods 0 Me+ R OMS Me Finally Vedejs has published a great deal of elegant work developing synthetic applications of sulphur-mediated 2,3-sigmatropic ring expansions. A recent review outlines the progress of this research.lW Fragmentations.-Barton and co-workers have continued to develop their decarboxy- lative functionalization method based on thiohydroxamic acid esters such as (1 16). According to recent publications these intermediates can now be converted into hydroperoxides R-0-OH sulphides selenides and tellurides R-X-R' and alkene addition or substitution products."' Scheme 37 shows one of these reactions the substitution of an allylic alkylthio-group by the radical R.40 0 R-C + \ c1 coz + T 1 Scheme 37 Two groups have discovered that the treatment of cyclic y-hydroxyalkyl stannanes with oxidizing agents results in fragmentation to give acylic enones or enals. Nakatani and Isoe used lead tetra-acetate as the oxidant with 5-and 6-membered carbocyclic stannanes.lo2 The reaction was shown to be stereospecific; a trans relationship between the tin and a P-alkyl substituent resulted in a trans-alkene as in the example in Scheme 38. The corresponding cis relationship led to a cis alkene. Fujita and co-workers used a combination of iodosylbenzene boron trifluoride etherate and dicyclohexylcarbodi-imideto accomplish similar transformation^.'^^ Their examples included the seven-membered carbocycle (1 17) which led to enal (118) on fragmentation.100 E. Vedejs Acc. Chem. Res. 1984 17 358. 101 D. H. R. Barton D. Crich and W. B. Motherwell J. Chem Soc. Chem. Commun. 1984. 242; D. H. R. Barton D. Bridon and S. Zard Tetrahedron Lett. 1984 25 5777; D. H. R. Barton D. Crich and G. Kretzschmar Tetrahedron Lett. 1984,25 1055; D. H. R. Barton and D. Crich Tetrahedron Lett. 1984 25 2787. lo' K. Nakatani and S. Isoe Tetrahedron Lett. 1984 25 5335. 103 M. Ochiai T. Ukita Y. Nagao and E. Fujita; J. Chem. Soc. Chem. Commun. 1984 1007. 274 A. €? Davis Reagents i Pb( OAc), benzene Scheme 38 0H An apparently useful y- ketoaldehyde synthesis has been reported based on the methoxide-catalysed fragmentation of gem-dichlorocyclopropyl ketones ( 1 19) (Scheme 39).As shown the second reductive step may be followed by acid work-up to give the y-ketoaldehyde directly or by basic work-up to give a protected a1 ternative. lo4 Reagents i MeONa MeOH; ii LiAIH4 p-dioxan; iii HCI aq. iv NaOH aq. Scheme 39 3 Functional Group Modifications Oxidation.-Additions to C=C. It is well-established that the halogenolactonization of 3-substituted pent-4-enoic acids can be achieved with excellent stereoselectivity (1,2-asymmetric induction). In contrast 1,3-asyrnmetric induction in this reaction (i.e. the stereoselective halogenolactonization of 2-substituted pent-4-enoic acids) has not been attained.However Yoshida and co-workers have observed almost complete stereoselectivity in an analogous cyclization performed on the related amides and thioamide~.'~~ For example the pentenamide (120) gave the trans-bromolactone (121) in 98% d.e. as shown in Scheme 40. The corresponding 104 0. G. Kulinkovitch I. G. Tischenko and N. V. Masalov Synthesis 1984 886. 105 Y. Tamaru M. Mizutani Y. Furukawa S.-i. Kawamura Z.-i. Yoshida K. Yanagi and M. Minobe J. Am. Chem. SOC.,1984 106 1079. Synthetic Methods thioamide cyclized similarly to a thiolactone. Unlike many of the more selective iodolactonizations these reactions take place under kinetic control ; equilibration of (121) with its cis-isomer gave a mixture in which the latter comprised 55% of the total.Reagents i N-bromosuccinimide DME,H,O; ii NaHCO aq. Scheme 40 Again unlike the earlier thermodynamically controlled iodolactonizations 1,2- asymmetric induction in this system was very poor. The cyclization of pentenamide (122) gave a ca. 1:1 mixture of diastereomers. The 1,3-asymmetric induction was rationalized in terms of a transition state (123). Transposition of substituent R and the C(2)-H would introduce a destabilizing interaction between R and one of the NMe groups. R Me -Me2NA0 Me' The iodocyclization of homoallylic carbamates has been used in a stereoselective 1,3-diol synthesis. It has now been shown that the introduction of a sulphonyl group on the carbamate nitrogen allows cyclization to take place through nitrogen instead of oxygen under appropriate conditions.The result is a moderately stereoselective synthesis of protected 1,3-arninoalcohols exemplified in Scheme 41.lo6 Analogous reactions on allylic carbonate derivatives gave protected anti-1,2-aminoalcohols but with rather lower stereoselectivity. II I 6.2 1 Reagents i I, K2CO3 Et,O Scheme 41 M. Hirarna M. Iwashita Y. Yarnazaki. and S. It6 Tetrahedron Lett. 1984 25 4963. 276 A. I? Davis The iodocyclization of allylic carbonate anions has been developed as a 1,2-diol synthesis. An extension now allows it to be used to make P-hydroxyketones (Scheme 42).'07 I Reagents i BuLi; ii CO,; iii I,; iv Amberlyst A26 F-form C6H6 reflux Scheme 42 Chamberlin et al.have studied iodohydrin formation from allylic alcohols and their derivatives."' When the double bond in the substrate is 1,2-disubstituted the reaction is generally regio- and stereo-selective. Addition to the double bond is trans with the iodine ending up on the carbon adjacent to the oxygen substituent and syn to it. For example treatment of alcohol (124) with iodine and an aqueous phosphate buffer gave almost exclusively the iododiol (125). 0-Alkylated or -silylated derivatives of ( 124) reacted similarly but with slightly lower selectivity. The stereochemical result can be rationalized by invoking a transition state (126) in accordance with the recent calculations of Houk et allo9 1 , I 4e A Bu 1 1 An interesting.new synthesis of optically pure dihydroxycycloalkanones is exemp- lified in Scheme 43.The stereochemistry of the osmylation of (127) is thought to be influenced both by the hydroxyl group (anti-directing) and the sulphoximino nitrogen (co-ordinating to osmium and thus syn-directing)."' Ph Ph I* I* 0 =ST= N Me 0=S,= N Me 127) Reagents i S-PhSO( NMe)CH2Li; ii separation of diastereomers by chromatography on silica gel; iii Me,N+-O- OsO cat.; iv heat Scheme 43 107 G. Cardillo M. Orena G. Porzi S. Sandri and C. Tomasini J. Org. Chem. 1984 49 701. 108 A. R. Chamberlin and R. Mulholland Jr. Tetrahedron 1984 40 2297. I09 K. N. Houk N. Rondan Y.-D. Wu J. Metz and M. Paddon-Row Tetrahedron 1984,40,2257. 110 C. R. Johnson and M. Barbachyn. J. Am. Chem.Soc. 1984 106 2459. Synthetic Methods The trans-addition of phenylselenenyl chloride to alkenes is well-known. Recently it was reported that the phenylseleno group in the product could be displaced by oxidation with chlorine followed by nucleophilic attack by chloride ion in a 'one-pot' operation. The net result is a convenient and apparently general syn-addition of chlorine to alkenes (Scheme 44)."' c1 I c1 c1 I c1- R'eR2 SePh Se+ /\Ph c1 Cl Reagents i PhSeCI; ii CI2; iii Bu,N+CI- Scheme 44 The epoxidation of alkenes is generally insensitive to steric hindrance. Rebek and co-workers have now synthesized the peracid ( 128) designed selectively to epoxidize less hindered alkenes.Il2 Whereas rn-CPBA shows very little selectivity between cis and trans alkenes (128) was found to epoxidize cis-2-octene 7.7-times faster than the trans isomer.Other Oxidations. A remarkably selective oxidation of alkenes to enones has been reported by Pearson and co-worker~."~ Scheme 45 shows an example in which a secondary alcohol in the substrate was unaffected. The catalytic species is thought to be Cr(C0)3(MeCN), formed from the chromium hexacarbonyl in situ. OH OH 60% Reagents i Bu'OOH (1.2 eq.) Cr(CO) (0.5 eq.) MeCN reflux Scheme 45 A. Morella and A. D. Ward Tetrahedron Leu. 1984 25 1197. 112 J. Rebek Jr. L. Marshall R. Wolak and J. McManis J. Am. Chem. Soc. 1984 106 1170. 113 A. J. Pearson Y.-S.Chen S.-Y. Hsu and T. Ray Tetruhedron Lett. 1984 25 1235. 278 A.P. Davis Two new methods have appeared for the oxidative functionalization of a carbon a to a carbonyl group. The oxaziridine (129) will oxidize enolates derived from ketones or esters and KHMDS to give a-hydroxycarbonyl compounds. This reagent is claimed to give cleaner conversion and greater stereoselectivity than the established alternatives; for example the enolate derived from lactone (130) was hydroxylated exclusively on the upper face to give alcohol (131).'14 A convenient method for brominating aldehydes and ketones employs a mixture of t-butyl bromide and DMSO. Carboxylic acids and esters do not react and ketones are selectively brominated at the more-substituted position. The active brominating agent is thought to be Me2SBr+Br-."5 r? r-? Ogo 0 8 Ph PhS02' H H The following sets of conditions have been reported to oxidize allylic alcohols selectively to enals or enones in the presence of saturated alcohols (i) K2Fe04 and PhCH,N( Et),'Cl- in benzene and aqueous sodium hydroxide;"' (ii) molecular oxygen with catalytic amounts of hydrated Ru02 in 1,2-di~hloroethane;"~ (iii) molecular oxygen with catalytic amounts of nitroxyl (132) and CuCl in DMF.Il8 In the last of these the active oxidant is thought to be the nitrosonium ion (133).All three methods preferentially oxidize primary allylic alcohols particularly (iii) which is completely ineffective with secondary analogues. In a modification of (iii) a stoicheiometric amount of CuC12 is used to generate the nitrosonium ion. These conditions will oxidize saturated primary alcohols fairly selectively in the presence of secondary alkanols.A method has been reported for the 'one-pot' conversion of primary alcohols to t-butyl esters (Scheme 46).'19 As indicated the reaction is presumed to proceed via the formation and oxidation of hemi-acetals ( 134) within the reaction mixture. 114 F. A. Davis L. Vishwakama J. Billmers and J. Finn J. Org. Chem. 1984 49 3241. 'Is E. Armani A. Dossena R. Marchelli and G. Casnati Tetrahedron 1984 40,2035. K. Kim Y. Chang S. Bae and C. Hahn Synthesis 1984 866. 117 M. Matsumoto and N. Watanabe J. Org. Chem 1984 49 3435. 118 M. F. Semmelhack C. Schmid D. Cortes and C. Chou J. Am. Chem. SOC 1984 106,3374. 119 E. J. Corey and B. Samuelsson J. Org.Chem. 1984,49 4735. Synthetic Methods ii[ R-CH,OH -[R-CHO] -R-C-OH ] -R-C0,Bu' 0But Reagents i py.Cr03(4eq.) CH2C12,DMF 15 min; ii AczO (10 eq.) Bu'OH (20 eq.) 16 h Scheme 46 A clean conversion of thiols to carbonyl compounds is shown in Scheme 47.12* The photochemical cleavage of phenacyl derivatives (135) to thiocarbonyl com-pounds (136) and the trapping of the latter by silyl nitronate (137) was previously established. The new development is the cleavage of adducts (138) to carbonyl compounds. OSiMe,Bu' (138) Reagents i PhCOCH,CI Et3N THF; ii hv (sunlamp). benzene (137) iii Bu,N+F- THF Scheme 47 A new conversion likely to prove particularly useful is the direct oxidation of secondary amines to nitrones by hydrogen peroxide catalysed by sodium tung- state.l2* When there is a choice of regiochemistry the method appears to give the more thermodynamically stable nitrone ; for example 2-methylpiperidine (139) is oxidized to the more substituted isomer (140) in 68% yield.E. Vedejs and D. Perry 1. Org. Chern 1984,49 573. I21 H. Mitsui S.-i. Zenki T. Shiota and S.4. Murahashi 1. Chem. SOC.,Chem. Commun. 1984,874. 280 A. P. Davis Optically pure sulphoxides are increasingly used in synthetic methodology. They have usually been prepared via a procedure involving the separation of diastereomeric menthyl sulphinates but it has long been recognized that a preferable route would be an efficient asymmetric oxidation of sulphides. Kagan and co-workers have come very close to this goal with a modification of the Sharpless conditions for asymmetric epoxidation.'22 In their best example treatment of p-tolyl methyl sulphide with a mixture of Ti(O'Pr), (R,R)-diethyl tartrate Bu'OOH and (critically) water in the ratio 1 :2 2 1 at -40 "C rising to -24 "C gave the R-sulphoxide in 95% yield and 93% e.e.It has been recognized for some time that a carbonyl carbon may be rendered nucleophilic by conversion to a hydrazone. It has now been shown that a vinylogous extension of this principle is possible. Thus electrophiles such as chlorine bromine iodine sulphenyl chlorides and sulphinyl chlorides react with crotonaldehyde hydrazone (141) to give substitution at C-3.'23 Scheme 48 shows bromination as an example and also demonstrates that the carbonyl group may be regenerated at the end of the sequence.I ii Mee/O 2Me+ ,,N-NMe2 Br Br Reagents i Me2N-NH,; ii Br, Et3N; iii H2C0 aq. HCI aq. Scheme 48 Finally reviews have been published on synthetic applications of (i) the palladium- catalysed oxidation of olefins to ketones (Wacker process)'24 and (ii) polyvalent iodine compounds (PhIC12 PhIO PhI02 etc).12' Reduction.-Hydrogenation of Carbon-Carbon Multiple Bonds. The homogeneous hydrogenation catalysts [Ir(cod)(py)(PCy,)]PF and [Rh(NBD)(DIPHOS-4)]BF4 (142) were both known to induce highly stereoselective hydrogenations of alkenes controlled by neighbouring hydroxyl groups. However neither had been tried on a broad range of acyclic alkenols. Employing hydrogen at one atmosphere pressure + BF,-122 P.Pitchen and H. Kagan Tetrahedron Lett. 1984,25 1049; P. Pitchen E. Dunach M. Deshmukh and H. Kagan J. Am. Chem. SOC.,1984 106 8188. lZ3 T. Severin G. Wanninger and H. Lerche Chem. Ber. 1984 117 2875. 124 J. Tsuji Synthesis 1984 369. 12' A. Varvoglis. Synthesis 1984 709. Synthetic Methods 281 Evans and Morrissey tested both catalysts on (143) (144) and a number of related alkenes. The results were disappointing until the pressure of hydrogen was raised to cu. 50 atmospheres; although the iridium catalyst was no more effective the rhodium catalyst gave very good selectivity as exemplified in Scheme 49. Under these conditions the rhodium catalyst was found stereoselectively to hydrogenate a wide range of cyclic and acyclic alkeno1s.126 Me+NRlaA M e Y N R M e wI NI R Me Me Me Me Me 93 7 9 91 Reagents i CH2CI, H (640 p.s.i.) (142) Scheme 49 A recent paper is claimed to give the best method yet reported for the selective cis-semihydrogenation of acetylenes.The reaction is performed under one atmo- sphere of hydrogen in a solvent mixture containing quinoline using a catalyst prepared from Pd(OAc), sodium hydride and t-amyl alcohol. Under these condi- tions 'self-terminating' semihydrogenation is possible.'27 An apparently convenient new method for simple hydrogenations and hydrogenolyses is the use of palladium on charcoal with sodium hypophosphite as a hydrogen source.128 Curbonyl Reductions. As usual there have been a large number of papers on the asymmetric reduction of ketones.Two of the more effective reagents were (i) the hydroaluminate (149 which reduces acetophenenone to give the S-alcohol in 97% e.e.,129 and (ii) a combination of [Rh(cod)Cl], Ph2SiH2 and the ligand (146) which hydrosilylates acetophenone to give the R-siloxane in up to 97.6% e.e.l3' Both reagents were much less selective with dialkyl ketones. Sih and Chen have reviewed the microbial reduction of ketones,131 often the best way of preparing simple alcohols enantioselectively. One of the more important examples is the reduction of P-ketoesters (147) by baker's yeast. The configuration and optical purity of the product appear to depend on the relative sizes of the two groups on either side of the carbonyl.Thus for R'=Me R2=Et the S-alcohol can be obtained in 97% e.e. while for R' R2=Et the R-isomer is produced in much 126 D. A. Evans and M. Momssey J. Am. Chem. SOC. 1984 106 3866. 127 J.-J. Brunet and P. Caubere J. Org. Chem. 1984 49 4058. 128 R. Sala G. Dona and C. Passarotti Tetrahedron Lett. 1984 25 4565. I29 K. Yamamoto H. Fukushima and M. Nakazaki J. Chem. SOC.,Chem. Commun. 1984 1490. 130 H. Brunner R. Becker and G. Riepl Organometallics 1984 3 1354. 131 C. J. Sih and C.-S. Chen Angew. Chem. Inr. Ed. Engl. 1984 23 570. 282 A. P. Davis lower optical purity. An elegant modification which considerably broadens the scope of the method is outlined in Scheme 50. An alkylthio group introduced at C-2 of the substrate ensures that this carbon will appear bulkier to the enzyme.The resulting alcohols have the S-configuration at C-3 both diastereomers being produced in 96% e.e. for a range of R' R2 and R3. Straightforward removal of the alkylthio group completes the sequence.'32 c SR2 sRZ SRZ Reagents:i baker's yeast preparation; ii m-CPBA; iii AI-Hg Scheme 50 There is great potential in many areas of natural-product synthesis for carbonyl reductions which are stereodirected by a pre-existing centre in the substrate. Oishi and Nakata have played an important part in developing such methods and have now reviewed their Recently it has been reported that bulky organosilanes can act as highly stereoselective reducing agents. Notably derivatives of a-hydroxy- and a-amino-ketones can be reduced to either erythru or threo products depending on the conditions (e.g.Scheme 51).'34 Brown continues to explore the use of boranes and hydridoborates as reducing agents for carbonyl compounds. Recent developments include the use of chloroborane complex (148) to reduce carboxylic acids to aldehyde^,'^^ said to be the first convenient method for accomplishing this conversion directly and the use of (149) in the stereoselective reduction of cyclic ketones.'36 The latter reagent is similar in selectivity to L~(BU')~BH ('L-selectride') but is advantageous in that it requires only a hydrolytic work-up as opposed to an oxidative one. 13* T. Fujisawa T. Itoh and T. Sato Tetrahedron Leu. 1984 25 5083. 133 T. Oishi and T. Nakata Acc.Chem. Res. 1984 17 338. 134 M. Fujita and T. Hiyama J. Am. Chem. SOC. 1984 106 4629. 135 H. C. Brown J. Cha B. Nazer and N. Yoon,J. Am. Chem. Soc. 1984 106 8001. 136 H. C. Brown J. Cha and B. Nazer J. Org. Chem. 1984 49 2073. Synthetic Met hods OH OH phQCHIPn ph*OCH,Ph + phsOCH2Ph Me Me Me Reagent i 96 4 Reagent ii 7 93 0 OH >98% d.e. >98% d.e. Reagents i PhMe2SiH Bu,N+F- cat. HMPA; ii PhMe2SiH CF3C02H Scheme 51 c1 K+ H Othe, Reductions. The reduction of aliphatic nitro-compounds to imines has generally been effected under conditions which immediately hydrolyse the imines to ketones. It is now reported that a combination of tributylphosphine and diphenyl disulphide will accomplish the reduction under conditions which are not only anhydrous but ~e1f-drying.l~' This allows the trapping of the imine in a number of ways for example by HCN addition to give an a-aminonitrile as in Scheme 52.A possible mechanism involves the interaction of the aci-form of the nitro-compound with an adduct (150) formed reversibly from the phosphine and the disulphide. (Scheme 53). Adduct . .. I II ph-om NOz -NH2 Reagents i (PhS), Bu3P,NaCN THF:ii AcOH Scheme 52 D. H. R. Barton W. Motherwell. and S. Zard Tetrahedron Lett. 1984. 25 3707. 284 A. P. Davis OH R' (150) >NH c--R'>-N' + Bu3P=0 + PHSjz R2 RZ Scheme 53 (150) also reacts rapidly with water to give tributylphosphine oxide and thiophenol. As implied in Scheme 53,the same conditions will also reduce oximes to imines.13* The Bamford-Stevens procedure for reducing ketones to alkenes has many poten- tial applications but is somewhat limited by the strongly basic conditions required.This year two methods have been reported which allow the same conversion to be accomplished under different and in some respects milder conditions. In one case the ketone was converted into a phenylaziridine hydrazone such as (151) which on thermolysis in decalin at 160 "C for 2 hours gave alkene (152) in 92% yield.'39 In the second method the ketone was converted into a vinyl triflate such as (153; X = OTf) which could be reduced to alkene (153; X = H) in 85% yield by tributylammonium formate in DMF with Pd(OAc)*( PPh3)* as ~atalyst.'~' n X NC 'Y Ph (151) Finally a paper by Zimmerman and Breslow describes a reaction which is unusual in that it was conceived out of an interest in enzyme mimicry but may form the basis for a general synthetic method of genuine usefulness.In nature the enzymatic interconversion of a-amino acids and a-keto acids is mediated by the coenzyme pair of pyridoxal (154) and pyridoxamine (155). In the presence of metal ions pyridoxamine itself may be used for the conversion of a-keto acids to a-amino acids but without (of course) the enantiospecificity of the enzymatic reaction. The analogue (156) was designed to remedy this deficiency. As shown in Scheme 54 the reaction requires the interconversion of two isomeric imines via a proton transfer. I38 D.H. R. Barton W. Mothewell E. Simon and S. Zard J. Chem. SOC.,Chem. Commun. 1984 337. I39 F. Mohamadi and D. Collum Tetrahedron Lett. 1984 25 271. 140 S. Cacchi E. Morera and G. Ortar Tetrahedron Lett. 1984 25 4821. Synthetic Methods (156) contains an amino group placed so that this may be accomplished intramolecularly on one face only of the intermediate. Hydrolysis of the products (157) gave amino acids of up to 90% e.e. and the authors point out that the possibility that (156) was not optically pure implies that the true enantioselectivity may be even greater.I4' NMe2 H (157) Scheme 54 Non-Redox Conversions.-Substitution at sp3-Hybridized Carbon. While it is generally fairly easy to induce an sp3 C-0 bond to cleave heterolytically few ways are known for cleavage of sp3 C -N.One well-established option is the conversion of a primary amine into a pyridinium compound followed by nucleophilic substitution in which the nitrogen leaves as part of the pyridine nucleus. Katritzky and his group have explored this area in depth and a review has appeared on their progress over the last four years.14* 141 S. Zimmerman and R. Breslow J. Am. Chem. SOC.,1984 106 1490. 142 A. R. Katritzky and C. Marson Angew. Chem. Inf. Ed. Engl. 1984 23. 420. 286 A. P. Davis A new method for C-N cleavage is exemplified in Scheme 55. The reagent (159) has a number of advantages over vinyl chloroformate used in an earlier version of the method; in particular decomposition of the initial products (160) occurs readily under neutral conditions.In general the order of ease of cleavage of alkyl groups is tertiary >> secondary > methyl > primary >> piperidine ring residue. As implied in Scheme 55 this allows substituted piperidines (158) to serve as a fairly general source of chlorides ( 161).'43 I Me OMe cAHzCl-+ C02 + Me-( -CN-.('-(cl + R-Cl OMe (161) Reagent i MeOH Scheme 55 The Cs' ion has been shown to be particularly useful as counterion for an anionic nucleophile in a number of SN2 macrocyclizations. As shown in Scheme 56 this has now been extended to the synthesis of azamacrocycles.'44 Ts Iiii H N Reagents i Cs2C03 DMF; ii Br-(CH2),6-Br; iii Na-Hg Na2HP0, MeOH Scheme 56 143 R.A. Olofson J. Martz J.-P. Senet M. Piteau and T. Malfroot J. Org. Chem. 1984 49 2081; R. A. Olofson and D. Abbott J. Org. Chem.. 1984,49 2795. 144 B. Vnesma J. Buter and R. M. Kellogg 1. Org. Chem. 1984 49 110. Synthetic Methods 287 The ring-opening of epoxides by attack of bromide ion at the less-substituted carbon requires essentially ‘non-electrophilic’ conditions. Obvious reagents to choose might be tetra-alkylammonium bromides or alkali metal bromides in dipolar aprotic solvents. However the ‘naked’ bromide ions provided by these sources seem to be relatively ‘hard’ inducing base-catalysed side-reactions in some substrates. It is reported that these difficulties can be avoided by using Li,NiBr, which appears to function as a source of unusually ‘soft’ Br-.*45 Substitution at spZ-Hybtidized Carbon.The macrolactonization of a complex hydroxyacid is a crucial step in many natural product syntheses. A new method outlined in Scheme 57 gave excellent yields for a number of 13- 14- and 16- membered macrocycles.’46 0 r Me \OH Me Me NMe2 Reagents i THF -60 to 0 “C; ii; CH,C12 or toluene 10-camphorsulphonic acid cat. Scheme 57 The conversion of an acid halide or ester into the corresponding carboxylate salt would generally be accomplished uia the acid itself and would probably involve an aqueous step. It is reported that a direct conversion which could be quite valuable in some circumstances can be accomplished by alkali-metal trimethylsilanolates (Me,SiO-M’) which thus act as anhydrous ‘0,-equivalent^'.'^' Alkyl diaryl sulphonium salts are of pivotal importance in sulphonium ylide chemistry because they offer only one site for deprotonation.Usually they must be made by the alkylation of diaryl sulphides and there is a clear need for practical methods for arylating alkyl aryl sulphides. A new procedure reported by Garst and co-workers is shown in Scheme 58. The sulphonium salts (162) are formed in acceptable yields and can be used in standard sulphonium ylid reactions such as cyclopropanation and epoxide f~rmation.’~~ 145 R. Dawe T. Molinski and J. V. Turner Tetrahedron Lett. 1984 25 2061. 146 H.-J. Gais Tetrahedron Lett. 1984 25 273. 147 E. Laganis and B. Chenard Tetrahedron Lett. 1984 25 5831. 14* B.McBride M. E. Garst and M. Hopkins J. Org. Chem. 1984 49 1824. 288 A. P. Davis 0 OH OMe Ar-S I i_ / BF, + 0 ;@/ BF A io R Ar -S Ar-S 0 R OH R OMe Reagents i CH2CI2 HBF,; ii CH2N2 Scheme 58 It has been known for some while that the reagent (163) will react with aromatic aldehydes to give the corresponding iminium salts. The reaction has now been generalized to aliphatic aldehydes. For example 4,4,4-trichlorocrotonaldehydecould be converted into the iminium fluoroborate (164) shown to be a powerful dienop hile. 149 Me Addition to C-C Multiple Bonds. The oxymercuration of a,P-unsaturated carbonyl compounds is known to be regiospecific placing the oxygen nucleophile in the P-position. It has now been shown that when applied to a-alkyl-8-oxygenated substrates such as (165) it is stereoselective as well (Scheme 59).lS0 The stereochemistry appears to be determined by the configuration at the y-carbon the new alkoxy group appearing anti to the alkyl substituent as in the example shown.The reaction should be generally useful in the synthesis of the 1,3-dioxygenated systems so common in natural products. A I,. II ..&yo .. I Me04 0 OEt t> OEt Me0 I/ bPh ( 165) > 90% d.e. Reagents i Hg(OAc), PhCH,OH CH2C12 HC10 aq.; ii NaBH, THF H,O Scheme 59 TeCl is known to add syn Markovnikov to simple alkenes. However it has recently been reported that with allylic esters rather different behaviour is observed. As shown in Scheme 60 addition is syn and 1,3 with stereospecific migration of the acyloxy group.The tellurium may be removed reductively to give chloroesters ( 166).”’ 149 A. Schwobel and G. Kresze Synthesis 1984 944. 1so S. Thaisrivongs and D. Seebach J. Am. Chem. Soc. 1983 105 7407. 151 L. Engman J. Am. Chem. SOC.,1984 106 3977. Synthetic Methods R' R3 R 1 q R 2 oAo ii 0'0 "YoR3 -+ RI&R? I R]&R' I Tea3Cl CI ( 166) Reagents i TeCI,; ii Raney Ni EtOH reflux Scheme 60 Miscellaneous. Conditions have been reported for the conversion of allylic selenides into a variety of protected allylic amines. Examples are shown in Scheme 61 chosen to illustrate the stereoselectivity of these reactions which presumably proceed via the [2,3]-sigmatropic rearrangement of selenimides ( 167).lS2 OH I UePh '3 HNTs 0 Reagents i ROANH2 (R = Bu' PhCH2) PrkNEt N-chlorosuccinimide MeOH; ii TsNCINa MeOH Scheme 61 R' I I52 J.Frankhauser R. Peevey and P. Hopkins Tetrahedron Lett. 1984 25 15; R. Shea J. Fitzner J. Fankhauser and P. Hopkins J. Org. Chem. 1984;49 3647. 290 A. P. Davis Esters of the form (168) have been proposed as useful protected carboxylic acids. As shown in Scheme 62 cleavage occurs under very mild conditions with Pdo catalysis giving the highly labile trimethylsilyl esters (169).lS3 + Me3Si-0 kR 0 Reagents i CH2C12 Pd(PPh,) (0.02eq.) Scheme 62 Acetal formation can be accomplished efficiently and conveniently with a new heterogeneous catalyst formed by derivatizing silica gel with alkoxysilane (170) and neutralizing the amino groups with hydrochloric acid.As it is only mildly acidic the catalyst is especially useful with substrates containing acid-sensitive Finally a new synthesis of nitro compounds employs the well-known reaction of azides RN3 with phosphines RiP to give iminophosphines RN=PRi which is then followed by cleavage with ozone to give RN02.155 (EtO),Si &NH 153 H. Mastalerz J. Org. Chem. 1984 49 4092. I54 F. Gasparrini M. Giovannoli D. Misiti and G. Palmieri Tetrahedron 1984 40,1491. 155 E. J. Corey B. Samuelsson and F. Luzzio J. Am. Chem. SOC.,1984 106 3682.

 



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