10 Synthetic Methods By P. A. CHALONER School of Chemistry and Molecular Sciences University of Sussex Brighton BN 1 9QJ 1 Introduction The format of this report remains the same as in previous years with a division of the material into two sections. The first details reactions in which carbon-carbon bonds are formed or broken and new carbon skeleta constructed whilst the second deals with functional group transformations. As always such a review must be selective; if readers feel that their own interests have been underrepresented over the past three years they have at least the consola- tion that a new reviewer with a new set of interests and prejudices will be taking over for 1989. 2 C-C Connection and Disconnection Connection of Separate Fragments.-Enolates and their Equivalents.Reactions of enolates have again figured strongly in C-C bond forming methodology this year. Excellent reviews have been published on asymmetric aldol methodology using boron enolates' and proline-catalysed reactions.2 Selective C-alkylation of P-diketones was achieved using terraethylammonium pyrrolidonate in DMF as the base; yields and selectivities were generally between 70 and 93Y0.~ C-Alkylation was also promoted under very mild conditions when catalysed by Co( PPh3)2Cl .4 A number of highly stereoselective alkylation reactions have been noted. The lithium enolates of t-butyl hydroxypentanoates could be alkylated using reactive electrophiles with reasonable diastereoselectivity (Scheme 1),5 and 99% diastereoselectivity was achieved in the alkylation of vinylogous urethanes derived from tetronic acids (Scheme 2).6 Enantioselective allylation of P-diketones was catalysed by a palladium complex of (1) in up to 81% enantiomeric excess.' Two new alkylation routes to quaternary chiral centres have been developed.The sequential dialkylation of trityloxymethylbutyrolactone proceeded with excellent stereoselectivity and was applied to the synthesis of optically active butyrolactones ' I. Paterson Chem Znd. (London) 1988 390. * C. Agami Bull. Soc. Chim. Fr. 1988 499. T. Shono S. Kashimura M. Sawamura and T. Soejima J. Org. Chem. 1988 53 907. A. Gonzalez J. Marquet and M. Moreno-Manas Tetrahedron Lett. 1988 29 1469. Y. Ukaji and K. Narasaka Bull. Chem. Soc. Jpn. 1988 61 571.R. H. Schlessinger E. J. Iwanowicz and J. P. Springer Tetrahedron Lett. 1988 29 1489. ' T. Hayashi K. Kanehira T. Hagihara and M. Kumada J. Org. Chem. 1988 53 113. 265 P. A. Chaloner R' = alkyl R2X = Me,SO, PhCH21 or BuI Reagents i LiN3,THF HMPA -100°C; ii R2X Scheme 1 i ii - Reagents i BuLi THF -78 "C 30 min; ii PhCH,Br -78 "C 30 min Scheme 2 (Scheme 3). Force field calculations and n.m.r. spectroscopic studies showed that the stereochemical course of the reaction was controlled by a unique conformation of the starting material.$ Selectivities in the alkylation of silyl ketene acetals by dienyl iron complexes ranged from 6 1 to >100 1 (Scheme 4).9 Me Me Reagents i LiNPri MeI THF -78 "C; ii LiNPri EtI THF -78 "C; iii HCI MeOH; iv LiAiH, THF 25 "C; v NaIO, H20; vi CrO, AcOH 25 "C Scheme 3 K.Tomioka Y.-S. Cho F. Sato and K. Koga J. Org. Chem. 1988 53 4094. A. J. Pearson,and M. K.O'Brien Tetrahedron Lett. 1988 29 869. Synthetic Methods CO,Me Fe(C0h OSiMe Reagents moMe ,CH2CI, MeCN A 6-18 h Scheme 4 Bismuth(II1) chloride has been used as an efficient catalyst for the aldol reaction but diastereoselectivities were generally low." The use of indium metal (commercial material which had not been specially activated) for Reformatsky reactions has been advocated; the reaction proceeds at room temperature.' ' Clay montmorillonite has been used as an efficient heterogeneous catalyst for the reaction of silyl enol ethers with aldehydes or acetals and also for Michael reactions of silyl ketene acetals.I2 There has been continued interest in diastereoselective aldol reactions.The prod- ucts of chelation control were obtained with high selectivity in the aldol reaction of t-butyl thioacetate enol silane to alkoxyaldehydes (Scheme 5).13 Germanium OBu I OBu OBu SBu' + wsBu~ 0 SBu' OH OH Reagent SKI Scheme 5 enolates may be prepared in situ from lithium enolates and Me,GeX. Diastereoselec- tivity in their subsequent reactions is controlled by the presence or absence of lithium halides (Scheme 6).14 The aldol condensation of chiral ethyl ketones has been controlled by the use of chiral boron reagents; diastereoselectivity was impressive (Scheme 7).15 Diastereo-and enatioselective reactions have been accomplished for a-silyl ketones; the reac- tion was again very selective and desilylation was readily achieved (Scheme 8).The product was used in an asymmetric synthesis of the agression pheromone sitophilure.I6 10 H. Ohki M. Wada and K. Akiba Tetrahedron Lett. 1988 29 4719. S. Araki H. Ito and Y. Butsugan Synth. Commun. 1988 18 453. 12 M. Kawai M. Onaka and Y. Izumi Bull. Chem. SOC.Jpn. 1988 61 2157 1237. 13 C. Gennari and P. G. Cozzi Tetrahedron 1988,44 5965. 14 Y. Yamamto and J. Yamada J. Chem. SOC.,Chem. Commun. 1988 802. 15 I. Paterson and M. A. Lister Tetrahedron Lett. 1988 29 585. 16 D. Enders and B. Bhushan Lohray Angew. Chem. Int. Ed. Engl. 1988 27 581. P. A. Chalontr 9R2ql?h R' R1 i..R2ii % RZVPh R' Reagents i LiNPr; Et,O -78 "C; ii Me,GeX; iii PhCHO -78 to -40 "C; iv remove LiCl Scheme 6 0 &OBn + 0 OH 0 7% 64% e.e (Bn = CH,Ph) + OTf Scheme 7 4'JJR Bu'Me2Si Me 55-68% 92-98% d.e. >98% ex. Reagents i Bu2BOTf Pr;NEt CHzClz -10 "C 2 h; ii RCHO; -78 "C; iii oxidative work-up; iv flash chromatography; v HBF, H,O THF 20 "C 1-2 days Scheme 8 Enantioselective aldol reactions between non-chiral starting materials have been mediated by chiral bases such as (2).17The reactions of a-isocyanoacetamides with aldehydes were catalysed by a gold complex of (3). It was considered that the " M.Muraoka H. Kawasaki and K. Koga Tetrahedron Letr. 1988 29 337. -0..+ Synthetic Methods X = N-Me piperazinyl isocyano group was bound to the gold and the remote amine functionality was hydrogen bonded to the enolate.The related esters reacted similarly.18 A new development in the Mukaiyama reaction has led to a one-pot synthesis of P-chloro carboxylic acids and esters (Scheme 9).The initial product a bis-0-silylated . .. ph+o*H "\=(" e3 + PhCHO -OSiMe3 R = alkyl or phenyl K Reagents i Ti& CH2C12 -60 "C (1 h) 20 "C (2 h); ii H20 Scheme 9 p-hydroxy acid is chlorinated by the TiC14 .19 The trimethylsilyl triflate-catalysed aldol-type reactions of silyl enol ethers with acetals or related compounds (Scheme 10) occurs via an acyclic transition state and exhibits moderate to high erythro Reagents CF3S03SiMe3 CH,C12 -78 "C Scheme 10 selectivity independent of the geometry of the starting material.'" a-Alkylation and a-alkylideneation of carbonyl compounds has been effected by Lewis acid-catalysed reaction of silyl enol ethers with a-chloro thioethers (Scheme 11).The problems of regio- and stereochemical control were considered in detail.21 The use of a chiral leaving group in a Claisen-type acylation has led to the construction of a quaternary chiral centre with high enantioselectivity (Scheme 12).22 Interesting enantioselective Michael reactions have been noted this year.In an intramolecular reaction catalysed by (R) -(+)-1-phenylethylamine (4) was converted into (5) with up to 90% e.e. in the presence of 5 A molecular sieves (Scheme 13); '* Y. Ito M. Sawamura M. Kobayashi and T.Hayashi Tetrahedron Lelt. 1988 29 6321; Y. Ito M. Sawamura E. Shirakawa E. Hagashizaki and T. Hayashi hid. p. 235; Tetrahedron 1988 44 5253. 19 M. Bellassoved J.-E. Dubois and E. Bertounesque Tetrahedron Lett. 1988 29 1275. 20 S. Murata M.Suzuki and R. Noyori Tetrahedron 1988 44 4259. 21 I. Paterson Tetrahedron 1988 44 4207. 22 Y. Nagao Y. Hagiwara T. Tohjo Y. Hasegawa M. Ochiai and M. Shiro J. Org. Chem. 1988,53 5983. 270 P.A. Chaloner Reagents i TiCI,; ii NaIO, MeOH-H20 (9 l) 20 "C 16 h Scheme 11 0 Ph ,L i ii Ph )-C02Me -Me '%02Me Reagents i LiNCy(Pr') Pr 'NhS; ii HMPA 1 Scheme 12 "'I Ph7 0 H 0 Reagents (R)-(+)-! -phenylethylamine 5 8 molecular sieves Scheme 13 the product will prove a useful building block in alkaloid synthesis.23 Mukaiyama has reported a wide range of enantioselective additions of tin enolates and enethio- lates to enones in the presence of chiral diamines (Scheme 14); enantiomeric excesses were generally in the region of 70Y0.~~ / Ph __* i-iv msMe Reagents i Sn(OTf), MeCS2Me Et N s CH2C12 -78 "C; ii wNHNp; N Me iii Me3SiOTf; iv H+ Scheme 14 23 Y.Hirai T. Terada and T. Yamazaki J. Am. Chem. SOC.,1988 110 958. 24 T. Yura N. Iwasawa T. Mukaiyama and K. Narasaka Chem. Lett. 1988 1021 1025. Synthetic Methods 27 1 Carbon-carbon bond formation specifically at the y-position of dienolates was achieved via the germanium-masked dienolates such as (6) (Scheme 15).25 Reagents i LiNPr; THF; ii. Me3GeX; iii PhCH(OMe), TiCl Scheme 15 Alyl Alkynyl and Alkenyl Anions and their Equivalents.Uses of allylsilanes in synthesis have been reviewed.26 a-Branched allylsilanes have been prepared in a simple regio- and stereocontrolled manner using BuLi-KOBu' as the base and careful' y controlling reaction condition^.^' y- Alkenyl- y- butyrolactones were opened in a regio- and stereoselective manner in the presence of [Me,O]+ by allylsilanes to give methyl 4,fGalkadienoates (Scheme 16).28 Reagents [Me,O][BF,] Scheme 16 A number of enantioselective allylations using allylboranes have been noted. Homoallyl alcohols were prepared by reaction of chiral crotylboronates such as (7) with achiral aldehydes; enantioselectivities in the presence of 4 A molecular sieves were generally excellent.29 (2-y-Alkoxyallyl)diisopinocamphenylboraneswere added to aldehydes with complete diastereoselection for the syn-product and good enantioselection (Scheme 17).30 T-Allylpalladium complexes prepared by oxidative addition of palladium(0) to ally1 derivatives are generally rather electrophilic.However in the presence of SnCI, 0-allyltin( ~v) compounds are formed and show considerable selectivity for 25 Y. Yamamoto S. Hatsuya and J. Yamada J. Chem. SOC.,Chem. Commun. 1988 1639. 26 A. Hosomi Acc. Chem. Res. 1988 21 200. 21 A. Mordini G. Palio A. Ricci and M. Taddei Tetrahedron Lett. 1988 29 4991. 28 M. Kawashima and T. Fujisawa Buff. Chem. SOC.Jpn. 1988 61 4051. 29 W. R.Roush K. Ando D. B. Powers,. R.L. Hatterman and A.D. Palkowitz Tetrahedron Lett. 1988 29 5579. 30 H. C. Brown P. K. Jadhav and K. S. Bhat J. Am. Chem. Soc. 1988 110 1535. 272 P. A. Chaloner 95:5 MeCHO / 4:96 Reagents i ,THF -78°C; ii ,THF. -78°C Scheme 17 reaction with aldehydes over ketones.31 The radical reaction between 2-bromo-N- benzoylglycine methyl ester and allylstannanes has provided a useful new route to a-alkylated amino acids.32 The couplings of ally1 halides with carbonyl compounds to give homoallyl alcohols via formation of a wide range of organometallics continues to attract attention. A two-phase system using electrochemically regenerated bismuth metal showed good selectivity for aldehydes over ketones,33 whilst cadmium-metal-medi- ated reactions with enones resulted in exclusively 1,2-additi0n.~~ Reaction of acrolein dimethylacetal with chromium(11) chloride gave the equivalent of an a-methoxylated allylchromium reagent which added to aldehydes with reasonable diastereoselectivity (Scheme 18).35 ?* 88 12 Reagents CrCI, Me3Sil THF -3O"C 3 h Scheme 18 31 Y.Masuyama R. Hayashi K. Otake and Y. Kurusu J. Chem. SOC.,Chem. Commun. 1988 44; Y. Masuyama J. P. Takahara and Y. Kurusu J. Am. Chem. Soc. 1988,110,4473; Y. Masuyama K. Otake and Y. Kurusu Tetrahedron Lett. 1988 29 3563. 32 J. E. Baldwin R. M. Adlington C. Lowe I. A. O'Neil G. L. Sanders C. J. Schofield and J. B. Sweeney J. Chem. SOC.,Chem. Commun. 1988 1030. 33 M. Minato and J. Tsuji Chem. Lett. 1988 2049. 34 S. Araki H. Ito and Y.Butsugan J. Organomet. Chem. 1988 347 5. 35 K. Takai K. Nitta and K. Utimoto Tetrahedron Lett. 1988 29 5263. Synthetic Methods 273 The syntheses physical properties and uses of tin( IV) alkynyl compounds have been reviewed.36A one-pot synthesis of primary 2-alkynylamides was accomplished by the reaction of R-C_C-SiMe with ClSO,NCO followed by work-up with aqueous Alkynyltin reagents underwent regio-and chemoselective addition to acylpyridines activated by methyl chloroformate to give dihydropyridine deriva-tives (Scheme 19).,* 2-Substituted but-3-yn-1-01s were obtained by ring opening of unsymmetrical epoxides with alkynyltitanium compounds (Scheme 20).39 R R' R' -nMe3 -+ R' +RZ-=-S d 1 + R' N R * RZ ,G d N I R2 I C0,Me C0,Me R' = H Me or OMe; R2 = alkyl 95:5-80:20 Reagents ClC02Me CH2C12,0 "C Scheme 19 R' R' = alkyl Ar or SiMe,; R2 = Ar alkenyl alkynyl or SiMe,; R3 = H alkyl or Ar; R4 = H or R2,R4 = cycloalkyl Reagents i BuLi THF 6-25 "C; ii CITi(OPr'), THF -50 "C; iii R3&:4 THF -50 "C; iv 25 "C 1-3 days R2 Scheme 20 Enantioselective addition of divinylzinc to aldehydes in the presence of (8) has been reported; good enantiomeric excesses were obtained for both aryl and alkyl aldehyde^.^' Stille's group has reported the carbonylation-coupling of RSnBu with aryl triflates to give ArCOR (R = alkenyl alkynyl or alkyl) in the presence of Pd(dppf)Cl .41 Metallation and alkylation of 4H-1,3-dioxin gave a new P-acylalkenyl anion equivalent (Scheme 21).42(E)-4-Lithio-4-tosylbutenonedimethylacetal(9) was used 36 C.Cauletti C. Fiolani and A. Sebald Gazz. Chim. Ztal. 1988 118 1. 37 P. C. B. Page S. Rosenthal and R. V. Williams Synthesis 1988 621. 38 R. Yamaguchi E. Hata and K. Utimoto Tetrahedron Lett. 1988 29 1785. 39 N. Krause and D. Seebach Chem. Eer. 1988 121 1315. 40 W. Oppolzer and R. N. Radinov Tetrahedron Lett. 1988 29 5645. 41 A. M. Echavarren and J. K. Stille J. Am. Chem. SOC. 1988 110 1557. 42 R. L. Funk and G. L. Bolton J. Am. Chem. SOC.,1988 110 1290. I? A. Chaloner \/ Reagents i Bu"Li THF -78 "C; ii Rx; iii A Scheme 21 Ts -)qCOMe TsrnOMe% i-iv ..-Tsyy 0 Li ... . .OMe COR OMe COR Reagents i NaTs I1; ii Et,N; iii HC(OMe)3; iv MeLi LiBr THF -20 "C; v RCOX -20 "C; vi HzO; vii HCI H,O 2-24 h Scheme 22 as a similar synthon (Scheme 22)?3 P-Hydroxyalkylation and conjugate addition of cyclohexenone was accomplished via (10) (Scheme 23).44 &+ 0siM e Bu' d ___* i ii iii iv & PPh3 COEt (10) OH Reagents i Bu'Me,SiOTf PPh3 THF; ii BuLi THF; iii CH,=CHCOEt Me3SiOTf THF -78 "C; iv [Bu,N]F; v PhCHO Me,SiOTf THF -78 "C Scheme 23 43 C.Najera and M. Yus J. Org. Chem. 1988 53 4708. 44 S. Kim and P. H. Lee Tetrahedron Lett. 1988 29 5413. Synthetic Methods Two examples of a-acylalkenyl anion equivalents are also of note. Reaction of but-3-en-2-one with aldehydes in the presence of DABCO resulted in addition at the a-position to give (ll) which was cyclized on heating.Dehydration gave 6,8-dioxabicyclo[3.2. lloctanes in up to 85% isolated yield the products being used in pheromone synthesis (Scheme 24).45 Reaction of enones with aldehydes in the Reagents i DABCO; ii 140 "C 10 h sealed tube Scheme 24 presence of H2R~(PPh3)4 and with no solvent gave a-methylene P-hydroxy ketones (Scheme 25).46 Ready access to P-acyl- and P-arylpropanals has been achieved using a new silylated organotin homoenolate equivalent (Scheme 26) ?7 Other Anions and their Equivalents. Ortho subsitution of methoxypyridines and 4-halogenopyridines has been accomplished via regioselective lithiation and reaction with electr~philes.~~ Metallation of benzylamine derivatives was also selective for the ortho position (Scheme 27).49 Reactions or organometallic reagents with aldehydes and ketones continue to attract attention.1,3-Anti asymmetric addition of organotitanium compounds to 45 :55->99 :1 Reagents H,Ru( PPh,), 40 "C 40 h Scheme 25 45 N. Daude U. Eggert and H. M. R. Hoffman J. Chem. Soc. Chem. Commun. 1988 206. 46 I. Matsuda M. Shibata and S. Sato J. Organomet. Chem. 1988 340,C5. 47 J.-B. Verlhac J.-P. Quintard and M. Pereyre J. Chem. SOC. Chem. Commun. 1988 503. 48 F. Marsais F. Trkourt P. BrCant and G. QuCguinier J. Heterocycl. Chem. 1988 25 81; D. L. Comins and D. H. La Munyon Tetrahedron Lett. 1988 29 773. 49 Y. Simig and M. Schlosser Tetrahedron Lett. 1988 29 4277. P. A. Chaloner SiMe3 SiMeJ i ii Bu3SnvOMe Bu3SndOMe / %Me3 I ArvOMe \ Ar OMe -Reagents i Bu"Li THF -78 "C; ii Me,SiCI; iii R'COCI Pd(PPh3)2C12 THF 65 "C; iv [Bu,N]F THF 0 "C; v ArBr Pd(PPh3)4 C,H, 110 "C Scheme 26 Reagents i BuLi THF hexane -78 to 0°C; ii CO,; ii H2Oz Scheme 27 &substituted aldehydes bearing a dithioacetal group has been reported to proceed with excellent stereoselectivity (Scheme 28)." Titanium was also used as a regio- I R' OH RZ R;_/\xcHo ss-ss It II 96 :4 syn:anti Reagents MeTiCI, 0 "C 30 min Scheme 28 and stereoselective control element for condensation of a-methoxyallylphosphine oxides with aldehydes (Scheme 29); in many cases the diastereoselectivities were better than 10 1." Alkyltitanium complexes of chiral diols such as (12) were used for enantioselective addition to aldehyde^.^' 50 Y.Honda and G. Tuchihashi Chem. Lett. 1988 1937. 51 E. F. Birse A. McKenzie and A. W. Murray J. Chem. SOC.,Perkin Trans. I 1988 1039. 52 H. Takahashi A. Kawabata M. Niwa and K. Higashiyama Chem. Pharm. Bull. 1988 36 803. 277 Synthetic Methods 0 0 0 It Ph2pe i-iv ~ OMe 2.5 1 Iv YPh OMe Reagents i LiNPr; THF -78 "C 30 min; ii TiCI,(OPr'), THF -78 "C 2 h; iii Pr'CHO -78 "C 1 h; iv NH,CI KF H20; v KOBU' THF 30min Scheme 29 Ph Ph Ph Ph Functionalized ketones have been prepared directly by the coupling of organocuprates with acid chlorides; esters nitriles halides epoxides and to some extent ketones were tolerated by the reaction condition^.'^ A convenient preparation of /3-keto sulphones was realized by the reaction of phenylsulphonylmethyl- enedilithium with acid chlorides; the reaction of the monoanion was ineffi~ient.'~ The primary aminomethylation of organometallic compounds using N,N-bis(trimethylsilyl)methylthiomethylamine has been de~cribed.~' Asymmetric induc- tion has been observed for the first time in the addition of Grignard reagents to nitrones (Scheme 30).Diastereoisomer ratios were in the range of 80:20 and the course of the reaction could be predicted using Cram's rule.s6 0-OH Reagents i MeMgCI Et20; ii H, Pd/C MeOH Scheme 30 53 R. M. Wehmeyer and R. D. Rieke Tetrahedron Lett. 1988 29 4513. 54 M. W. Thomson B. M. Handwerker S. A. Katz and R. B. Belser J. Org.Chem. 1988 53 906. 55 L.Fiocca M. Fiorenza G. Reginata A. Ricci P. Dembech and G. Seconi J. Organomet. Chem. 1988 341 C23. 56 M. P. Cowling P. R. Jenkins and K. Cooper J. Chem. SOC.,Chem. Commun. 1988 1503. P. A. Chaloner Two papers have reported the enantioselective addition of dialkylzinc reagents to enones in the presence of dibutylnorephedrine and a nickel salt. Enantiomeric excesses up to 50% were a~hieved.~' Very high selectivity was noted in the conjugate addition of methyltitanium isopropoxide to an optically pure sulphoxide (Scheme 31); the product was used in the synthesis of P-~etivone.~' Conjugate addition to Ar = 4-MeOC6H Reagents i MeTi(OPr'), THF; ii Raney Ni EtOH Scheme 31 chiral 5-trimethylsilycyclohexenoneled to a synthesis of chiral alkylated cyclo- hexenones (Scheme 32).59 High-pressure asymmetric Michael additions of thiols and nitromethane to enones in the presence of (+)-quinidine gave optical yields of up to 60%.60 >96% e.e.Reagents i RMgX CuI; ii CuCI, DMF 60 "C 25-90 min Scheme 32 The Michael addition of a-alkoxy organocuprates to enals proceeded with a high degree of syn selectivity and the products could be readily converted into cis-disubstituted butyrolactones. Compound (13) was used similarly as the synthetic equivalent of a carbonyl ylide in a synthesis of tetrahydrofurans (Scheme 33):' The substitution of enol ethers by Grignard reagents has been reported to occur in the presence of nickel complexes. Trisubstituted alkenes could be prepared by the reactions of 6-alkyl-3,4-dihydro-2H-pyrans (Scheme 34).62 Allylsilanes were prepared in moderate to good yields in the reactions of dithioacetals with trimethyl- silylmethylmagnesium chloride (Scheme 35).63 57 K.Soai T. Hayasaka S. Ugajiu and S. Yokoyama Chem. Lett. 1988 157; K. Soai S. Yokoyama T. Hayasaka and K. Ebihara J. Org. Chem. 1988 53 4148. 58 G. H. Posner and T. G. Hamill J. Org. Chem. 1988 53 6031. 59 M. Asaoka K. Shima and H. Takai J. Chem. SOC.,Chem. Commun. 1988 430. 60 A. Sera K. Takagi H. Katayama and H. Yamada J. Org. Chem. 1988 53 1157. 61 R. J. Linderman and J. R. McKenzie Tetrahedron Lett. 1988,29,3911; R. J. Linderman and A. Godfrey J. Am. Chem. SOC.,1988 110 6249. 62 L. Jalander Synth. Commun.1988 18 343; P. Kocienski N. J. Dixon and S. Wadman Tetrahedron Lett. 1988 29 2353. 63 Z.-J. Ni and T.-Y. Luh J. Chem Soc. Chem. Commun. 1988 1011. 279 Synthetic Methods OSiMe3 __* i ii iii __+ O-\ R R (13) Me,SiCI; ii Et3N hexane; iii TiCI4 CH2C12 -78 "C Scheme 33 Reagents MeMgBr Ni(PPh3),C12 C6H6 A 36 h Scheme 34 n ,SiMe3 Reagents Me3SiCH2MgCI Ni( PPh3)2C12 Et,O C6Hs A Scheme 35 Two groups have given details of nucleophilic additions to iron tricarbonyl complexes of a,P-unsaturated ketones to give 1,Qdiketones (Scheme 36).@ Some Reagents i MeMgBr Et20 -78 "C 7 h; ii ButBr Scheme 36 new organomanganese compounds have been investigated; opening of epoxides and ethers and coupling with ally1 and vinyl derivatives have been described (Scheme 37).65 64 T.N. Danks D. Rakshit and S. E. Thomas J. Chem. Soc. Perkin Trans. 1 1988 2091; H. Kitahara Y. Tozawa S. Fujita A. Tajiri N. Morita and T. Asao Bull. Chem. Soc. Jpn. 1988 61,3362. 65 P. De Strong and D. R. Sidler J. Org. Chem. 1988 53 4892; K. Fugami J.-I. Hibino S. Nakatsukasa S.Matsubara K. Oshima K. Utimoto and H. Nozaki Tetrahedron 1988,44,4277. P. A. Chaloner R'VSR2 -% R'wSiR + R:Si Reagents i Me3SiMn(CO), CH2=CHC02Me Et,O 5 kbar 14-96 h; ii Me,SiMn(CO), hv MeCN CH2=CHC02Me 25 "C 1-12 h; iii H20 02,25 "C; iv (R:Si),MnMgMe Scheme 37 Cerium-mediated reactions of Grignard reagents have been used in the preparation of functionalized alkylsilanes (Scheme 38); the reactions of lactones were also improved.66 SiMe3 OMe -(Me0)2CHL./ Me& nMgCl + Me0 &C02Me i %Me3 OH iii (MeO),CH& %Me3 Reagents i CeCl,; ii Si02 Scheme 38 Methyleneation and Alkylideneation.A new synthesis for CH2(A1C1R),.2Et20 from aluminium metal and dichloromethane has been described the procedure being carefully monitored for safety. This is an excellent reagent for the methyleneation of ketones.67 The synthesis of vinylthiazoles and the related substituted benzothiazoles by Wittig reactions has been described. Subsequent cleavage of the heterocycle provides a sequence for a three-carbon homologation of aldehydes (Scheme 39).68The prepara- tion and reactions of diisopropoxypropyltriphenylphosphoniumbromide another three-carbon homologating agent have been described (Scheme 40).69Polyconju-gated aldehydes have been prepared using the new Horner- Wadsworth-Emmons reagent (14) with work up by flash ~hromatography.~' The allylideneation of 66 T.V. Lee J. R. Porter and F. S. Roden Tetrahedron Lett. 1988 29 5009. 67 A. M. Piotrowski D. B. Malpass M. P. Boteslawski and J. J. Eisch J. Org. Chem. 1988 53 2829. 68 A. Dondoni G. Fantini M. Fogagnolo A. Medici and P. Pedrini Tetrahedron 1988 44,2021. 69 J. Viala and M. Santelli Synthesis 1988 395. 'O T. Rein B. Akermark and P. Helquist Acta Chem. Scand. Ser. B 1988 42 569. Synthetic Methods 281 Me +/ 1-ivl Me Reagents i KOBU' C6H6 25 "C 48 h; ii Pr'CHO; iii Mel MeCN A 5-24 h; iv NaBH, MeOH -10 "C 20 min; v HgCI, H20 MeCN 15 min Scheme 39 ... + Br-bCHO JdL. Ph3P *CH( OPr i)2 iii CH(OPri)2 -RlL ivl R2 R 1bCHO Reagents i PPh, HBr Pr'OH CH,CI, lOT 10h; ii HC(OPr'), OT 30min; iii R'R'CO BuLi hexane; iv TsOH THF A 20 min Scheme 40 0 II (EtO) P (14) aldehydes was accomplished by successive formation of a palladium-ally1 complex from an allylic alcohol followed by transformation into an ylid and a Wittig reaction (Scheme 41).'l Vinylsilanes have been prepared stereoselectively from carbonyl compounds and Me,SiCH2Cl (Scheme 42).'* The corresponding silylated Grignard reagent was used in a nickel-catalysed reaction with dithioacetals (Scheme 43).73 Miscellaneous. Unsymmetrical pinacols have been prepared by the reactions of diary1 ketones with dialkyl ketones in the presence of ytterbium metal.Reactions with epoxides were also Reductive coupling of enones (Scheme 44) was N. Okuado 0. Uchikawa and Y. Nakamura Chem. Left. 1988 1449. 72 J. Barluenga J. L. Fernandez-Simon J. M. Concellon and M. Yus Synthesis 1988 234. 73 Z.-J. Ni and T.-Y. Luh J. Org. Chem. 1988 53 2129. 74 Z. Hou K. Takamine 0. Aoki H.* Shiraishi Y. Fujiwara and H. Taniguchi J. Chem. SOC. Chem. Commun. 1988 668. P. A. Chaloner PhvOH + C,H,,CHO -Ph-C7H15 4 1 E E E Z via PhvOCONHPh -PhA 5phu$R, I+ PdL2 PhNH- PhNH- 1 Ph"PR3 Reagents Bu,P Pd(PPh,), MeCN PhNCO A 5 h Scheme 41 Me3SiCH2Cl -+ Rj_/SiMe3 R2 >95'/0 E Reagents i Bu"Li TMEDA THF -78 to -60 "C 40 min; ii R1R2C0 -60 to -45 "C (R' R2 = H alkyl aryl); iii LiNp THF -78 to 20 "C 12 h; iv NH,CI H20 Scheme 42 Reagents Ni(PPh3)2C12 Et,O C6H6 or THF A 12 h Scheme 43 i ii 4 Reagents i Mg MgBr, Et20 Me,SiCl; ii H20 Scheme 44 promoted by Mg/MgBr2.75 Titanium tetrachloride was used for the coupling of imines to symmetric vicinal amines (Scheme 45); diastereoisomeric ratios were in the region of 90 10 for most substrate^.^^ A new synthesis of 1,2-glycol monoethers via samarium diiodide-mediated decar- bonylation of a-alkoxy acyl chlorides has been reported.Yields were not particularly high but a large number of examples were noted (Scheme 46).77Sm12 was also 75 J.-M. Pons and M. Santelli Tetrahedron Lett. 1988 29 3679. 76 P. Mangeney T.Tejero A. Alexakis F. Grosjean and J. Normant Synthesis 1988 255. 77 M. Sasaki J. Collin and H. B. Kagan Tetrahedron Lett. 1988 29 4847. Synthetic Methods R1 R' ,R1 kNR2 * H' R~NH 'NHR~ R~NH 'NHR~ R',R2 = alkyl or aryl Reagents i HgCI, Mg THF 25 "C 20 min; ii TiCI4 L25 "C 30 min 0 "C 12 h Scheme 45 + MeOCH2COCl -4 Reagents i SmI, THF 25 "C 1 min; ii HCI H20 Scheme 46 used for the reductive coupling of a,P-unsaturated esters with carbonyl compounds. The reaction proceeds uia radical intermediates after one-electron transfer and lactones were obtained in 40-82% yield.78 Aliphatic aldehydes were converted into the homologous methyl ketones using trimethylsilyldiazomethane followed by work-up with aqueous HCl.79 A new one- carbon homologation of alkyl and aryl halides was accomplished using a bis(trimethylstanny1)benzopinacolate-mediatedfree radical carbon-carbon bond forming reaction (Scheme 47) Ketones (ArCOR) were prepared from carboxylic RX + CH2=NOCH2Ph -* RCH2NHOCH2Ph Me3Sn0 OSnMe Reagent Ph#Ph Ph Ph Scheme 47 acids and aromatic hydrocarbons using 2-trifluoromethylsulphonyloxypyridine as the coupling agent.The reaction probably involves transacylation to give the acylated 2-hydroxypyridine followed by electrophilic attack on the arene.81 TiC1,-mediated additions of isocyanides R'NC to aldehydes R2CH0 gave a-hydroxycarboxamides R2CH(OH)CONHR' in very high yield in a Passerini-type reaction.82 Alcohols and ethers were functionalized in the a-position in very high yield in a photochemical reaction with (15) (Scheme 48).83 78 S.Fukuzawa A. Nakanishi T. Fujinami and S. Sakai J. Chem. SOC.,Perkin Trans. 1 1988 1669. 79 T. Aoyama and T. Shioiri Synthesis 1988 228. D. J. Hart and F. L. Seely J. Am. Chem. SOC.,1988 110 1631. 81 T. Keumi K. Yoshimura M. Shimada and H. Kitajima Bull. Chem. SOC.Jpn. 1988 61 455. 82 D. Seebach G. Adam T. Gees M. Schiess and W. Weigard Chem. Ber. 1988 121 507. 83 K. Ogura A. Yanagisawa T. Fujino and K. Takahashi Tetrahedron Lett. 1988 29 5387. I? A. Chaloner SMe SMe R’CH-( RICH=( -I-MeOH I_ [ S0,Tol SOzTol OH (15) 96‘10 SMe SMe RICH-( (15) + 2A0 SO2Tol -S02Tol -RICH R2 Reagents i hv PhCOPh 30 min; ii NaH R21; iii [H,O]+ Scheme 48 Cyc1ization.-Free radical cyclizations have continued to attract considerable atten- tion.Samarium diodide was used to initiate intramolecular pinacol couplings and for an intriguing double cyclization of 2-allyloxybenzoic acid chlorides to give cyclopropanols (Scheme 49).84 Approaches to the synthesis of carbacepham and Reagents Sml, 25 T 1 min Scheme 49 carbacephem systems by radical cyclization in the presence of Bu,SnH have been described (Scheme 50).85A tandem radical cyclization approach to the hexahy- drobenzofuran skeleton for avermectin synthesis has been described (Scheme 51).86 C02Me Reagents i CH2=CHCH2Br lithium hexamethyldisilazide THF -78 “C 20 min; ii Bu,SnH AIBN CsHa A 16 h Scheme 50 84 G. A. Molander and C. Kenny J.Org. Chem. 1988 53 2132; M. Sasaki J. Collin and H. B. Kagan Tetrahedron Lett. 1988 29 6105. 85 T. Kametani S.-D. Chu A. Itoh S. Maeola and T. Honda Heterocycles 1988 27 875; T. Kametani S.-D. Chu A. Itoh S. Maeda and T. Honda J. Org. Chem. 1988 52 2683. 86 P. J. Parsons P. A. Willis and S. C. Eyley J. Chem. SOC.,Chem. Commun. 1988 283. Synthetic Methods Reagents Bu,SnH AIBN C6H6 80 "C Scheme 51 A practical synthesis of bicyclopentanedicarboxylic acid has been described (Scheme 52); this is a useful starting material for the preparation of low molecular weight and polymeric bicy~lopentanes.~~ Reagents i :CBr2; ii MeLi pentane Et20 -78 "C; iii MeCOCOMe hv 8 h; iv NaOBr dioxan 0 "C (1 h) 25 "C (3 h) 50"C (1 h) Scheme 52 The intramolecular addition of allylsilanes to carbonyl electrophiles occurred in the presence of TiC14 to give predominantly the products of the chelation-controlled reaction (Scheme 53); five- six- and seven-membered ring compounds were pre- pared in this way." 00 R' = OEt NMe, NEt, or Me; R2 R3= alkyl or aryl Reagents TiCI, CH,C12 -78 "C Scheme 53 Two rhodium-catalysed reactions have proved useful.In (16) the rhodium-cata- lysed insertion of the diazoketone moiety occurred regioselectively with the ester group steering the insertion away from the P-methylene group (Scheme 54).89 Regiospecific cyclization of 1,6-enynes to give methylenecyclohex-2-enes was cata- lysed by Wilkinson's complex.90 87 P. Kaszynski and J. Michl J. Org. Chem. 1988 53 4593.88 G. A. Molander and S. W. Andrews Tetrahedron 1988 44 3869. a9 G. Stork and K. Nakatani Tetrahedron Lett. 1988 29 2283. 90 R. Grigg P. Stevenson and T. Worakun Tetrahedron 1988 44 4961. P. A. Chaloner COCHNz COZEt Reagents Rh,(OAc), CH2C12,25 "C Scheme 54 Cycloadditions and Annu1ations.-Reactions Forming Six-membered Rings. Both increased selectivity and an increased reaction rate in Diels- Alder reactions were achieved by the adsorption of the reactants on chromatography adsorbents." Quino- dimethanes were generated by proton-induced elimination of 2-hydroxyalkylben- zyltrimethylstannanes and various cycloaddition reactions were de~cribed.~' There has been considerable interest in enantioselective Diels- Alder reactions.The benzyl ester of (S)-proline was used as a chiral auxiliary in a Lewis acid- catalysed reaction (Scheme 55).93 Menthyloxyfuranone has found uses as a chiral I R:S = 97~3,endozexo = 9416 Reagent TiCI, -10°C Scheme 55 dienophile; selectivities were generally excellent.94 Many examples of diastereoselec-tive cycloadditions of chiral a$-unsaturated N-acyloxazolidinones have been described (Scheme 56).95 The asymmetric hetero-Diels- Alder reaction between the diene (17) and benzaldehyde was catalysed by a chiral Lewis acid (18) (Scheme 57).96 NAO P+ Q -hRi0 R' d CON RZ' (excess) ?-J Ri Reagents Et,AICI CH,CI, -100 "C 2-5 min Scheme 56 91 V. V. Veselovsky A. S. Gybin A. V. Lozanova A. M. Moiseenkov W. A. Smit and R. Caple Terrahedran Left.1988 29 175. 92 H.Sano H. Ohtsuka and T. Migita J. Am. Chem. Sac. 1988 110 2014. 93 H. Waldmann J. Org. Chem. 1988 53 6133; Angew. Chem. Znt. Ed. Engl. 1988 27 274. 94 B. L. Fennga and J. C. De Jong J. Org. Cfiem. 1988,53 1125. 95 D. A. Evans K. T. Chapman and J. Bisaha J. Am. Chem. SOC.,1988 110 1238. 96 N. Maruoka T. Itoh T. Shirasaka and H. Yamamoto J. Am. Chem. Sac. 1988 110 310. Synthetic Methods OMe 0 aPh 0' I 77% 95% e.e. Reagent (18) Ar = Ph or 3,5-Me,C,H3 Scheme 57 A tandem cycloaddition-radical cyclization procedure (Scheme 58) has been found to be a widely applicable strategy for the formation of polycyclic systems.97 Reagents. i benzyne generated from 2-diazobenzenecarboxylate; ii Bu,SnH AIBN C,H6 A Scheme 58 A new strategy for annulation of cyclohexenones involved successive conjugate addition coupling cyclopropanation and rearrangement (Scheme 59).98 Reactions Forming Fivemembered Rings.Nitrones have again this year been extremely popular dipoles and an interesting synthesis of p-amino ketones was accomplished via isoxazolines (Scheme 60).99 Isoxazolines prepared from aryl nitrones and alkynes were rearranged to enamine derivatives. loo A highly diastereoselective intramolecular nitrone cycloaddition to an a$-unsaturated ester was used to prepare a P-lactam precursor (Scheme 61)."' Ultrasound considerably accelerated the cycloaddition of unreactive conjugated nitrones with unactivated alkenes.''* 97 T. Ghosh and H.Hart J. Org. Chem. 1988,53 2396. 98 J. P. Marino and J. K. Long J. Am. Chem. SOC.,1988,110 7916. 99 V. Mancuso and C. Hootele Tetrahedron Lett. 1988,29 5917. 100 A. Liguori R. Ottana G. Romeo G. Sindoria and N. Uccella Tetrahedron 1988,44,1247,1255. 101 R. Annunziata M. Cinquini F. Cozzi and L. Raimondi Terrahedron Lerr. 1988,29 2881. 102 D. R.Borthakur and J. S. Sandhu J. Chem. Soc. Chem. Commun. 1988 1444. P. A. Chaloner OSiEt CN I 8+ ___* cL/s 5 equivalents H Reagents i -78 "C; ii Et,SiCI Et3N THF -78 to 0 "C; iii PhSOz-OTs Pd(PPh,),CI, CuI LiCI THF 67 "C; iv N2CHC02Et C,H, bis-( N-benzylsalicylaldiminato)Cu( II) 85 "C; v CsF MeCN 80 "C Scheme 59 Reagents i CHCI, A; ii H, Pd/C Scheme 60 i.' R3 \ N-0 SOIPh 0 /L..,/COCl Reagents i R2 ,CH,CI, Py,0-25 "C 30 min; ii 03,CH,CI2 -78 "C 30min; iii Me,S; iv R3NHOH; v DBU CCI, A Scheme 61 Synthetic Methods Cycloaddition of nitrile oxides with N-acryloyl sultams has been used in the preparation of optically active A2-isoxazolines (Scheme 62).'03 Functionalized cyclic ethers were prepared by a novel intramolecular cycloaddition of nitrile oxides to alkenes (Scheme 63).'04 Reagents i RCNO hexane ii L-Selectride THF 25 "C Scheme 62 i-iii zo BrMe2CCN=NOSiMe3 -0 H Reagents i F-; ii CH,=CHCH,OH; iii NaOCl Scheme 63 A convenient alternative approach has been described for the synthesis of 2-acetoxymethyl-3-trimethylsilylpropene,a useful annulating agent.lo5 The outcome of palladium-catalysed cyclopentannulation using (19) or (20) depends strongly on the nature of the leaving group (Scheme 64).The unusual regioselectivity of the reaction arises from and may be explained by a combination of steric and electronic factors.' O6 A new class of organobis(cuprate) reagents has been prepared and used in a wide range of spiroannulation reactions (Scheme 65).'07 Other Ring Sizes. Copper(11) supported on Nafion perfluorinated ion exchange polymer has proved to be an efficient cyclopropanation catalyst. Unlike rhodium catalysts which were leached at a significant rate the supported catalyst could be reused at least ten times."' Fischer carbene complexes have been used as 103 D. P. Curran B. H. Kim J.Daugherty and T. A. Heffner Tetrahedron Lett. 1988 29 3555. 104 A. Padwa U. Chiacchio D. C. Dean A. M. Schoffstall A. Hassner and K. S. K. Murthey Tetrahedron Letf.,1988 29 4169. 105 B. M. Trost M. Buch and M. L. Miller J. Org. Chem. 1988 53 4887. 106 B. M. Trost S. M. Migrani and T. N. Nanninaga J. Am. Chem. SOC.,1988 110 1602. 107 P. A. Wender and A. H. White J. Am. Chem. Soc. 1988 110 2218. 108 W. A. Nugent and F. J. Waller Synth. Commun. 1988 18 61. P. A. Chaloner I Z SiMe (19) I Z SiMe3 (20) Z = electron withdrawing group Reagents i Pd( PPh3)4 C6H6 Scheme 64 -0 CuSPhLiC>PhLi 0 ~ c ,+ CuSPhLi I ~ 96% U Reagents THF -15 "C 1 h Scheme 65 cyclopropanation agents in the preparation of donor-acceptor substituted cyclo-propanes and vinylcyclopropanes derived from 1,3-dienes (Scheme 66).'09 Intramolecular [2 + 21 cycloadditions of ketenes to alkenes has been used in the preparations of a bicycloheptanones (Scheme 67)."' The enantiospecific synthesis R R-,COzMe -.+ Ph+C02Me Me0 R = Me Ph or C0,Me Reagents (OC)5Cr- 80-1 10 "C solvent Ph Scheme 66 A.Wienand and H. U. Reissig Tetrahedron Lett. 1988 29 2315; M. Buchert and H. U. Reissig ibid. p. 2319. 1LO B. B. Snider and M. Niwa Tetrahedron Lett. 1988,29,3175; S. Y. Lee Y. S. Kulkami B. W. Burbaum M. I. Johnston and B. B. Snider J. Org. Chem. 1988 53 1848. Synthetic Methods 29 1 Reagents i LiNPr; THF HMPA -78 "C; ii CH2=CHCH2CH2CH2Br -78 "C 3 h; iii 25 "C; iv NaH c~cococ~, C6H6 A 30 min; v Et3N C,H,Me A Scheme 67 of substituted p-lactams could be achieved by the annulation of Schiff bases from D-glyceraldehyde acetonide with acyl halides and base (Scheme 68); the products can be used as intermediates for the preparation of alkaloids carbohydrates and amino acids."' Reagents i R1NH2 Et,O 0°C; ii R2CH2COCI Et3N CH,CI, -20°C Scheme 68 Rearrangements and Fragmentations.-A number of useful intramolecular ene reac- tions have been described this year including diastereoselective reactions using FeC1,-A1,O3 or ZnBr as the catalysts (Scheme 69).' l2 An enantioselective reaction Me02C / Me02C Me02C $&JyJ+/* C02Me C02Me C02Me 98.8% 1.2% Reagents FeCI,-AI,O, CH2C12 -78 "C 1 h Scheme 69 was catalysed by a chiral titanium alkoxide complex (Scheme 7O),ll3 and it is perhaps also noteworthy that enantioselective ene reactions of prochiral aldehydes with alkenes have been catalysed by a chiral aluminium complex.' l4 A novel Wittig rearrangement has been used as a new method for the diastereoselective preparation of 1,2-diols (Scheme 7 1).Steric interactions in the 111 D. R.Wagle C. Garai J. Chiang M. G. Monteleone B. E. Kurys T. W. Strohmeyer V. R. Hegde M. S. Manhas and A. K. Bose J. Org. Chem. 1988 53 4227. 112 L. F. Tietze and U. Beifuss Synthesis 1988 359; L. F. Tietze U. Beifuss M. Rulher A. Ruhlmann J. Antel and G. M. Sheldrick Angew. Chem. Inl. Ed. Engl. 1988 27 1186. 113 K. Narasaka Y. Hayashi and S. Shimada Chem. Lett. 1988 1609.'14 K. Manuoka Y. Hoshino T. Shirasaka and H. Yamamoto Tetrahedron Lett. 1988 29 3967. P. A. Chaloner 63'/o 16% Ph Ph >98% e.e. Reagents ph<lpH TiCI,(OPr'), CFCI,CFCI, 4 A molecular sieves ..xOH Ph 'Ph Scheme 70 \\ Reagents i Bu'Me,SiOTf Et3N CH2C12 5 "C 5-10 min; ii BuLi THF -78 fa -65 "C 5 h Scheme 71 transition state impose the strong anti syn preferen~e."~ In a diastereoselective reaction (Scheme 72) stereocontrol was exerted over three contiguous chiral centres.' l6 ButMe2Si0 OH Ill + (B) SiMe Bu'MezSiO OH (A) (B) (C) Z-isomer i_ 77% 94% d.e. 4% d.e. E-isomer -L 93'/o 10% d.e. 50% d.e. Reagents BuLi THF -78 "C 5 h Scheme 72 115 E. Nakai and T. Nakai Tetrahedron Left.,1988 29 5409.116 E. Nakai and T. Nakai Tetrahedron Lett. 1988 29 4587. Synthetic Methods The Beckmann fragmentation of cyclic ketoximes could be directed by the presence of a silyl group to give o-unsaturated nitriles with good selectivity (Scheme 73)."' AcO Reagents CF,S03SiMe, CH2CI2 0-25 "C Scheme 73 Azacyclic compounds were prepared by rearrangement and ring expansion of N-(arylsu1phonoxy)amines (Scheme 74).' l8 Reagents (4-N02-C,H,S0,0) EtOH -78 "C Scheme 74 A synthesis of ketoalkylcyclopropanols has been described; they could be readily converted into cyclopentanones (Scheme 79.' l9 1-Siloxy-1 -alkylcyclopropanes reacted with aryl triflates in the presence of palladium-ally1 complexes to give RCOCH2CH2Ar in moderate to good yields.'20 EtO OMgBr Reagents i PrSNMgBr ; ii NaOH H20 A Scheme 75 3 Functional Group Modifications Oxidation.-Additions to C=C.There have been numerous reports of new epoxida- tion reactions. Hydrogen peroxide was used to epoxidize water-insoluble non-activated alkenes in the presence of quaternary ammonium tetrakis(diperoxotungst0) 117 H. Nishiyama K. Sakuta N. Osaka H. Arai M. Matsumoto and K. Itoh Tetrahedron 1988,44 2413. 11* R. V. Hoffman and G. A. Buntain 1. Org. Chem. 1988 53 3316. 119 J. T.Carey and P. Helquist Tetrahedron Lett. 1988 29,1243. 120 S.Aoki T.Fujimura E. Nakamura and I. Kuwajima J. Am. Chem. Soc. 1988 110,3296. P. A. Chaloner phosphates(3-); the reaction was tolerant of esters and ketones.121 Stereospecific epoxidation of cis- and trans-stilbene was effected by oxygen transfer from the oxaziridinium salt (21) The enantioselective Sharpless epoxidation was used in syntheses of vinyl di01s'~~ and chiral ph~sphines,'~~ in each case by regio- and stereoselective opening of the initially formed epoxide (Scheme 76).Further details have been given of the asymmetric dihydroxylation of alkenes via ligand-accelerated osmium ~atalysis.'~~ I OH OH OH PPh2 OH R+ PPh2 + R,& PPh2 I A OH PPh2 Reagents i Bu'OOH Ti(OPr'), (+)-L-DIPT,CH2Clz,-20 "C,20 h; ii [Bu,N]F 0 "C,30 min; iii Bu'OOH Ti(OPr'), (+)-L-DET CH2CI2,-20 "C,3 h; iv TsCI Py,-1O"C 20 h; v LiPPh, THF Scheme 76 Other Oxidations. Again this year there have been reports of a range of selective oxidizing agents for secondary alcohols.Reagents included Bu'OC1 in the presence of pyridine'26 and H,O,-tricetylpyridinium 12-t~ngstophosphate.'~~ Both primary and secondary alcohols were oxidized by pyrazinium chlorochromate,128 and phenyl-dichlorophosphatewas used as an activating agent for DMSO in the Pfitzner- 121 C. Venturello and R. D'Aloisio J. Org. Chem. 1988 53 1553. 122 G. Hanquet X.Lusinchi and P. Milliot Tetrahedron Lett. 1988 29 3941. 123 T. Matsumoto Y. Kitano and F. Sato Tetrahedron Lett. 1988 29,5685. 124 H.Brunner and A. Sicheneder Angew. Chem. Int. Ed. Engl. 1988 27 718. 125 E. N. Jacobsen I. Marko W. S. Mungall G. Schroder and K. B. Sharpless J. Am. Chem. Soc. 1988 110 1968. 126 J. N. Milovanovic M.Vasojevic and S. Govkovic J. Chem..Soc. Perkin Trans. 2 1988 533. 127 K.Yamawaki H. Nishihara T. Yoshida T. Ura H. Yamada Y. Ishii and M. Ogawa Synth. Commun. 1988 18 869. 128 G. J. S. Doad J. Chem. Res. (S) 1988 270. Synthetic Methods 295 Moff at 0~idation.l~~ A convenient and efficient one-pot procedure for the direct conversion of aldehydes into esters using bromine as an oxidant has been devised (Br2 H20 MeOH NaHCO, 22 "C 3-5 h); secondary hydroxyl groups protected as MOM MEM Bn Bz Ph,Bu'Si or acetal derivatives all survived the reaction condition^.'^' a-Mesylation of ketones and a-dicarbonyl compounds was effected by PhI(0H)- (OMS) but few reactions were regio~elective.'~' Chiral a-hydroxy ketones were prepared by oxygenation of ketone enolates in the presence of P(OEt) and a chiral phase transfer catalyst such as a cinchonine salt.'32 The enantioselective synthesis of protected a-hydroxy aldehydes and ketones via the hydroxylation of metallated chiral hydrazones has been reported; enantiomeric excesses were generally better than 90% (Scheme 77).13 Oxidative ring cleavage of epoxides by CF3S03H-DMS0 provided an alternative preparation of a-ketols which was used in an approach to the taxane~.',~ n 0 Reagents i ;ii LiNPr; THF 0 "C;iii PhANSOzPh ,-85 "C; iv NaOH DMF; R3 NHz R3 v PhCH,CI; vi 03,CH2CI, -78 "C Scheme 77 The oxidation of nitroalkanes to ketones occurred in the presence of the cobalt Schiff base complex [Co(salpr)] under mild conditions and in excellent yields.'35 Ketoximes were prepared in a regiospecific manner from aryl-conjugated alkenes and ethyl nitrite in the presence of cobalt(~~).'~~ The enzyme isolated from Acinetobacter NC1B 9871 effected Baeyer-Villiger oxidation of meso-cyclo-hexanones such as (22) in better than 98% e.e.(Scheme 78).13' Asymmetric oxidation of selenides has been accomplished under Sharpless epoxi- dation condition^,'^^ whilst the asymmetric oxidation of sulphides by Bu'OOH was catalysed by the enzyme chlor~peroxidase.'~~ '29 H.-J. Liu and J. M. Nyangulu Tetrahedron Lett. 1988 29 3167. 130 D. R. Williams F. D. Klingler E. E. Allen and F. W. Lichtenthalen Tetrahedron Lett. 1988 29 5087. 131 J. S. Lodaya and G. F. Koser J. Org. Chem. 1988 53 210. 132 M.Masui A. Ando and T. Shioiri Tetrahedron Lett. 1988 29 2835. 133 D. Enders and V. Bhushan Tetrahedron Lett. 1988 29 2437. 134 B. M. Trost and M. J. Fray Tetrahedron Lett. 1988 29 2163. 135 A. Nishinaga S. Morikawa K. Yoshida and T. Matsuura Nippon Kagaku Kaishi 1988 487. 136 T. Okamoto K. Kobayashi S. Oka and S. Tanimoto J. Org. Chem. 1988 53 4897. 137 M. J. Taschner and D. J. Black J. Am. Chem. Soc. 1988 110 6892. 138 T. Shimizu M. Kobayashi and N. Kamagita Sulfur Lett. 1988 8 61. I39 S. Colonna N. Gagero A. Manfredi L. Casella and M. Gullotti J. Chem. SOC.,Chem. Commun. 1988 1451. l? A. Chaloner (22) 73% > 98% e.e. Reagents enzyme from Acinetobacter NClB 9871 glycine NaOH pH 8 NADPH (recycled) Scheme 78 Reduction.-Hydrogenation of Carbon -Carbon Multiple Bonds.The uses of ammonium formate in catalytic hydrogen transfer have been reviewed.',' Another asymmetric synthesis of carboxylic acids containing two adjacent chiral centres [such as (23)] has been achieved by hydrogenation in the presence of (24) with good selectively (92% e.e.).141 The fact that the two enantiomers of (25) are reduced at different rates in the presence of (BINAP)Ru(OAc) has been used in a practical kinetic resolution of the ally1 alcohol although recoveries were not particularly high.'42 A number of selective reductions of the carbon-carbon double bond in enones and unsaturated nitro compounds have been noted; use of the Hantzsch ester as reductant gave particularly successful re~u1ts.l~~ Enones were also reduced to ketones by conjugate addition using (Ph,PCUH)6 .la Alkylamines were obtained from nitroalkenes using LiEt,BH in the presence of borane; mechanistic studies suggested a reaction sequence involving 1,2-addition of Et,B to a nitroso intermediate.14' Hydrogenation of Carbonyl Compounds.A general method has been developed for the selective reduction of ketones in the presence of enones using NaBH in MeOH-CH,Cl (1:1) at -78 0C.146In selective carbonyl reduction methylaluminium bis(di-t-butylmethylphenoxide)may be used as a protective group for the more reactive carbonyl group in the molecule (Scheme 79).'47 The reduction of dicarbonyl compounds to hydroxycarbonyl derivatives and unsaturated carbonyl compounds to allylic alcohols was catalysed by zirconocene or hafnocene complexes using propan-2-01 as the red~ctant.'~' 140 S.Ram and R. E. Ehrenkaufer Synthesis 1988 91. 141 T. Hayashi N. Kawamura and Y. Ito Tetrahedron Lett. 1988 29 5969. 142 M. Kitamura I. Kasahara K. Manabe R. Noyori and H. Takaya J. Org. Chern. 1988 53 708. 143 Y. Inoue S. Imaizumi H. Itoh T. Shinya H. Hashimoto and S. Mujano Bull. Chem. SOC.Jpn. 1988 61 3020; M. Fujii ibid. p. 4029. 144 W. S. Mahoney D. M. Breslensky and J. M. Stryker J. Am. Chem. SOC.,1988 110 291. 145 G. W. Kabalka J.-Z. Gal N. M. Goudgaon R. S. Varma and E. E. Gooch Organometallics 1988,7,493. D. E. Ward C. K. Rhee and W. M. Zoghaib Tetrahedron Lett. 1988 29 517. K. Maruoka Y. Araki and H. Yamarnoto J.Am. Chem. Soc. 1988 110 2650. T. Nakano S. Umano Y. Kino Y. Ishii and M. Ogawa J. Org. Chem. 1988 53 3752. 146 147 148 Synthetic Methods 297 + ph~~cH2)4~0 HO [product ratio 7 1 :31 Reagents MeAl-(- 0 )* DIBAH -78 "C Scheme 79 The diastereoselective reduction of P-hydroxy ketones was effected using [Me,N]-[HB(OAc),] at -40 "C (Scheme 80). The reaction seems to involve complex forma- tion by exchange and intramolecular delivery of h~dride.'~~ Reagents [Me,N][HB(OAc),] -40 "C 5 h Scheme 80 Enantioselective reactions have again been widely reported. Baker's yeast is once more in vogue with asymmetric reductions of P-and y-nitro ketone^,'^' a-keto ester^,'^' and N-substituted acet~acetamides.'~~ A particularly intriguing example involved the first partial kinetic resolution of a planar chiral ketone-chromium tricarbonyl complex (Scheme 81).'53 Stereoselective reductions of prochiral ketones and of a prochiral imine were effected using an optically active methyldihydropyridine (26) and magnesium per- chlorate.Steric interactions were dominant and the hydroxy group of the reagent was used to anchor the ~ubstrate.'~~ Most of the chiral systems which have been used to reduce prochiral ketones have given selective results only with aryl alkyl I49 D. A. Evans K. T. Chapman and E. M. Carreira J. Am. Chem. Soc. 1988 110 3560. 150 K. Nakamura Y. Inoue J. Shibahara S. Oka and A. Ohno Tetrahedron Lett. 1988 29 4769. 151 K. Nakmura K. Inoue K. Ushio S.Oka and A. Ohno J. Org Chem. 1988 53 2589. 152 M. Kawai K. Tajima S. Mizuno K. Niimi H. Sugioka Y. Butsugan A. Kozawa T. Asano and Y. Imai Bull. Chem. Soc. Jpn. 1988 61 3014. 153 J. Gillois D. Buisson R. Azerad and J. Jaouen J. Chem. Soc. Chem. Commun. 1988 1224. 154 A. I. Meyers and J. D. Brown Tetrahedron Letr. 1988 29 5617. 298 P. A. Chaloner fyiqyl.+~+& 'OH ,' Cr(c0) C~(CO) C~(CO) C~(CO) 47% S-endo 5% S-exo ki 51% e.e. 71% e.e. ?H m cr(CO) 48% R-endo Reagents i baker's yeast glucose H,O EtOH; ii NaBH 25% e.e. Scheme 81 ketones and related substrates. A new reagent potassium diisopropylidene- glucofuranosylboratabicyclononane (27) however has been used with simple aliphatic ketones; thus (28) was reduced with 84% e.e.'55 Other Reductions.Acid chlorides have been reduced to aldehydes using the hyper- valent silicon reagent (29); yields were generally in excess of 95%.Is6 Highly activated uranium metal was prepared from UC14 and [(tmeda)Li],[Np]. With this reagent both benzoin and benzil were rapidly reduced to diphenylacetylene. A maximum of 30% could be isolated since further reduction to cis-stilbene was rapid.lS7 H.C. Brown B. T. Cho and W. S. Park J. Org. Chem. 1988 53 1231. lS6 R. J. P. Corriu G. F. Lanneau and M. Perrot Tetrahedron Lett. 1988 29 1271. 15' B. E. Cahn and R. D. Rieke J. Organomer. Chem. 1988 346 C45. Synthetic Methods 1,4-Bis(diphenylhydrosilyl)benzenegave better results in the deoxygenation of ace- tates than Ph,SiH."* A one-pot conversion of phenols into arenes has been described (Scheme 82); the intermediates in the reaction could also be coupled with alkenyl and alkynyl metal derivative^.'^^ OH Y = C1 OMe CHO or CH=CH Reagents i RS02F Et3N; ii HC02H Pd(PPh3)2C12 DMF 80°C 8-20 h Scheme 82 The first really successful asymmetric hydrogenation of imines has been reported using rhodium complexes of Cycphos as the catalysts.The presence of added iodide ion proved to be crucial to the reaction which in the best case gave up to 91% e.e. Only the imines of aryl aldehydes and ketones gave successful results.'60 Asymmetric reduction of oxime ethers was accomplished using borane in the presence of (30). The anti-ethers generally gave (S)-products and the syn-substrates (R)-amines in 79-92'/0 e.e.16' Nitropyridines could be reduced to aminopyridines using a titanium(0) slurry; conditions were mild and selectivities high.162 A range of aromatic nitro compounds were reduced to azoxy compounds by sodium benzenetellurolate prepared in situ from NaBH and catalytic PhTeTePh.I6 Non-redox Conversions.-Substitution at sp3- Hybridized Carbon.The regio- and chemoselective ring opening of epoxides with trimethylsilyl azides has been noted; attack of azide was at the less-substituted carbon atom.'64 Regioselective opening of 2,3-epoxy alcohols (31) with a titanium azide complex was also regioselective (Scheme 83); the 3-azido-1,2-diols were transformed into a-amino acids in two steps.'65 Opening of (32) with sodium benzenethiolate supported on zeolite CaY 158 H.Sano T. Takeda and T. Migita Chem. Lett. 1988 119. 159 Q. Chen and Y. He Synthesis 1988 896. 160 G. Kang W. R. Cullen M. D. Fryzuk B. R. James and J. P. Kutney J. Chern. Soc. Chem. Comrnun. 1988 1466. 161 Y. Sakito Y. Yoneyoshi and G. Suzukamo Tetrahedron Lett. 1988 29 223. 162 M. Malinowski Bull. SOC.Chim. Belg. 1988 97 51. 163 K. Ohe H. Takahashi S. Uemura and N. Sugita J. Chem. SOC.,Chem. Commun. 1988 591. 164 M. Emziane P. Lhosle and D. Sinou Synthesis 1988 541. 165 M. Caron P. R. Cartier and K. B. Sharpless J. Org. Chern. 1988 53 5185. P. A. Chaloner OH 0 -&OH + &OH (31) OH 31:l N3 Reagents Ti(N3)2(OPri)2,C6H6 70°C 5 min Scheme 83 was also regioselective.'66 Enantioselective cleavage of cyclohexene epoxide was effected by halogenodiisopinocampenylboranes (33); for X = I the reaction was close to completely enantio~elective.'~~ There continues to be considerable interest in the functionalization of enolates and related reactions.P-Dicarbonyl compounds were converted into azides using PhIO-Me,SiN (Scheme 84).16*Electrophilic sulphenylation of silyl ketene acetals N3 Reagents PhIO Me3SiN, CHCI, 25 "C (2 h) A (3 h) Scheme 84 derived from 3-hydroxy esters provided a useful diastereoselective synthesis of protected epoxyalcohols (Scheme 85).'69 Enantioselective fluorination of P-dicar-bony1 compounds was accomplished using (34),170 and a-selenylation with (35) both in about 60% e.e.l7' Me3Si0 OSiMe3 OSiMe3 ArSCl RdOEt -R&C02Et 4-I SAr SAr syn :anti = 20 :80-6 :94 Scheme 85 166 M.Onaka K. Sugita H. Takeuchi and Y. Izumi J. Chem. SOC.,Chem. Commun. 1988 1173. 167 N. N. Joshi M. Srebnik and H. C. Brown J. Am. Chem. SOC.,1988 110 6246. 168 R. M. Moriarty R. K. Vaid V. T. Ravikumar B. K. Vaid and T. E. Hopkins Tetrahedron 1988,44 1603. 169 G. Guanti L. Banfi E. Narisano and S. Thea Chem. Lett. 1988 1683. 170 E. Differding and R. W. Lang Tetrahedron Lett. 1988 29 6087. 171 C. Paulmier F. Outurquin and J.-C. Plaquevent Tetrahedron Lerr. 1988 29 5889. Synthetic Methods 301 Adamantanes have been brominated at the bridgehead position under mild condi-tions using Br,-H,O at 30°C.’72Silyl ethers may be directly converted into alkyl bromides using BBr .173 The selective formation of P-glycosidic linkages in oligosaccharide synthesis has been accomplished using an alkylsulphenyl triflate as activator.17* Desoxysugars have been prepared via a radical reaction of (36) (Scheme 86); migration of 0-benzyl (Cc AcO- 6 -Br AcO--0Ac )-Br )i.OAc AcO AcO (36) Reagents Bu3SnH AIBN C6H6 A 10 h Scheme 86 groups was also possible.175 Asymmetric cyclization of butylene dicarbamates was catalysed by chiral ferrocenylphosphine palladium complexes (Scheme 87).176 PhNHCOz-OzCNHPh -OH NHPh 80% 73% e.e.Reagents i . ii KOH MeOH A pph2 ‘CH(CH~OH)? * ’PPh2 \ ‘Pd-Cl c1I Scheme 87 Substitution at sp2-Hybridized Carbon.The lithiation of secondary allyl-and methal-lylamines was both regio-and stereoselective; reactions of the dilithio species with 1j2 C. A. Grob and P. Sawlewicz Helv. Chim. Acfa 1988 71 1508. S. Kim and J. H. Park J. Org. Chern 1988 53 3111. 174 F. Dasgupta and P. J. Garegg Carbohydr. Rex 1988 177 C13. 175 B. Giese S. Gilges K.-S. Groninger C. Lamberth and T. Witzel Liebigs Ann. Chem. 1988 615. 176 T. Hayashi A. Yamamoto and Y. Ito ‘Tetrahedron Left. 1988 29 99. 302 P. A. Chaloner a range of electrophiles was investigated (Scheme 88).'77 Vinylic chlorination of enones was achieved through Lewis acid-catalysed reaction with PhSeOC1.'78 Li I R~NH i ii R'N ........ Li ... . 1v R'NH R2 R2 R2 Reagents i BuLi; ii Bu'Li; iii MeSSMe; iv H,O Scheme 88 New procedures for the regeneration of carbonyl compounds from nitrogenous derivatives have been developed.Amberlyst 15 was a mild and selective acid catalyst,'79 and Dowex 50 proved to be selective for the derivatives of ketones over those of aldehydes.'80 Hydrazones were converted directly into geminal dibromides using two equivalents of bromine in Et,N-ether the reaction being particularly successful for sterically hindered substrates.18' Reactions that include amide hydrolysis and ester formation were found to be greatly accelerated by being performed in sealed Teflon vessels in a microwave oven.lB2 Aminolysis of prochiral dicarboxylic anhydrides was achieved using (37); diastereoisomeric excesses of up to 94% were reported.'83 More examples of the enantioselective formation and hydrolysis of acid derivatives catalysed by enzymes have been reported this year.Solvent effects were very impor- tant in the asymmetric acylation of amino alcohols by porcine pancreatic lipase (PPL) (Scheme 89).'84 Irreversible and highly enantioselective acylation of 2-halogeno-1-arylethanols in organic solvents was catalysed by a lipase from Pseudornonas Jluore~cens.'~~ A lipase from Pseudornonas species was used in the selective hydrolysis of (38); both products were obtained in better than 99% e.e.IB6 Enantioselective hydrolysis of open chain and cyclic nitropropane diol diacetates 3.7 HNKS 1 S Ar OAc 177 J. Barluenga F. J. Fafianis F. Foubelo and M. Yus J. Chem. Soc.Chem. Commun.,1988 1135. 17' N. Kamigata T. Satoh and M. Yoshida Bull. Chem. Soc. Jpn. 1988 61 449. 179 R. Ballini and M. Petrini J. Chem Soc. Perkin Trans. 1 1988 2563. 1an B. C. Ranu and D. C. Sarkar J. Org. Chem.. 1988 53 878. I81 F. S. Guziec and L. J. SanFilippo Synthesis 1988 547. 182 R. N. Gedye F. E. Smith and K. C. Westaway Can. J. Chem. 1988 66 17. 183 Y. Nagao Y. Hagiwara Y. Hasegawa M. Ochiai T. Inoue M. Shiro and E. Fujita Chem Lett. 1988 381. 184 V. Gotor R. Brieva and F. Rebolledo J. Chem. Soc. Chem. Commun. 1988,957. 185 J. Hiratake M. Inagaki T. Nishioka and J. Oda J. Org. Chem. 1988 53 6130. 186 K. Laumen and M. P. Schneider J. Chem. Soc. Chem. Commun. 1988 598. Synthetic Methods 3 03 TOH i_ -OH + TOAc NH2 NHAc NHCOMe (*) R > 95% e.e.S > 95% e.e. Reagents PPL EtOAc 25 "C 20 h Scheme 89 was effected by pig liver esterase (Scheme 90). Elimination of water or acetic acid from the products gave derivatives of nitroallyl alcohols which undergo diastereoselective Michael additions or SN2' substitution^.'^^ 8O-90% >95% e.e. Reagents pig liver esterase Scheme 90 Addition to Carbon- Carbon Multiple Bonds. The silylcupration of allene (Scheme 91) gave initially (39) a synthon for trimethylenemethane.'88 Substantial regio- and SiMe2Ph H,C=C=CH 4''-iii iv ,=cSiMezPh SiMe2Ph I X (39) Reagents i (PhMe,Si),CuLi THF -78 "C 1 h; ii I, THF 1 h; iii BuLi THF -7O"C 30min; iv X+ (DzO MeI HCHO Me,CO or MeCH=CHCHO) Scheme 91 stereochemical control was noted in the rhodium( I)-catalysed hydroboration of alkenes in both cyclic and acyclic systems (Scheme 92).lS9The rhodium-BINAP- catalysed hydroboration of norbornene proceeded in up to 64% e.e.19' The palladium-catalysed asymmetric disilylation of enones gave p-silyl enol ethers which could be hydrolysed and oxidized to give P-hydroxy ketones with good enantioselectivity (Scheme 93).I9l 187 M.Eberle M. Egli and D. Seebach Helv. Chim. Actu 1988 71 1. lX8 P. Cuadrado A. M. Gonzalez F. J. Pulido and I. Fleming Tetrahedron Lett. 1988 29 1825. 189 D. A. Evans G. C. Fu and A. H. Hoveyda J. Am. Chem. Soc. 1988 110 6917. 190 K. Burgess and M. H. Ohlmeyer J. Org. Chem. 1988 53 5178. 191 T. Hayashi Y. Matsumoto and Y.Ito J. Am. Chem. SOC.,1988 110 5579. P. A. Chaloner i + 50:50 i + ii + 90:lO Reagents i 9-BBN THF 25 "C; ii Rh(PPh,),CI Scheme 92 qPh OH 90°/o 87% e.e. Reagents i PhCl,SiSiMe, (BINAP)PdCI,; ii MeLi; iii [H,O]+; iv HBF,; v H20 Scheme 93 Miscellaneous. A number of interesting aldehyde addition reactions have been reported. The addition of hydrazoic acid in the presence of TiC14 and an alcohol gave a-azido ethers gas-phase thermolysis or photolysis of which gave mainly imino ethers.'92 Addition of trimethylsilyl cyanide to amino aldehydes in the presence of a Lewis acid may give either (40) the chelation control product or (41) from a non-chelation-controlled reaction. Using ZnBr2 (41) was the main product but in the presence of TiC14 (40) was formed with reasonable ~electivity.'~~ Using the Lewis acid prepared from Ti(OPri)2C12 and (42) asymmetric addition occurred in 61-93% e.e.194 Asymmetric hydrocyanation of aryl aldehydes was effected by KCN-HOAc in the presence of the enzyme oxynitrilase present in almond fl0~r.l~' 192 A.Hassner R.Fibiger and A. S. Amarasekara J. Org. Chem. 1988 53 22. 193 M. T. Reetz M. W. Drewes K. Harms and W. Reif Tetrahedron Lett. 1988 29. 3295. 194 H. Minamikawa S.Hayakawa T. Yamada N. Iwasawa and K. Narasaka Bull. Chem. SOC.Jpn. 1988 61 4379. 195 J. Brussee E. C. Roos and A. van der Gen Tetrahedron Lett. 1988 29 4485. Synthetic Methods An improved synthesis of vinyl iodides and phenylvinyl selenides from hydrazones has been described (Scheme 94).'96 dz- 90% Reagents i N-t-butyl-N',N',N",N"-tetramethylguanidine, 12 Et20 30 min; ii 90 "C no solvent 1 h; iii N-t-butyl-N',N',N,N"-tetramethylguanidine, PhSeBr THF Scheme 94 Again there have been a number of reports of new alcohol-protecting groups.THP ethers of allyl propargyl and benzylic alcohols were obtained in good to excellent yields and without dehydration when [Ph,PH]Br was used as the catalyst under mild condition^.'^' Primary alcohols reacted selectively with Ph,Si(OBu')Cl- Et3N; the alcohols protected a; ROSiPh,OBu' were stable to acid but could be readily deprotected with fluoride The diol(43) was monoprotected with good selectively (Scheme 95).'99 4,4'-Dinitrobenzhydryl ethers have found applications as protecting groups with good stability towards both acid and base.," (431 Reagents HC(OMe), D-camphorsulphonic acid CH2CI, 25 "C 24 h; ii DIBAH hexane CH,C12 -78 "C (30 min) 0 "C (10 min) Scheme 95 '5-6 D.H. R. Barton G. Bashiardes and J.-L. Fourrey Tetrahedron 1988 44 147. 197 V. Bolitt C. Mioskowski D.-S. Shin and J. R. Falck Tetrahedron Lett. 1988 29 4583. 198 J. W. Gillard R. Fortin H. E. Morton C. Yoakim C. A. Quesnelle S. Daignault and Y. Guindon J. Org. Chem. 1988 53 2602. 199 M. Takasu Y.Naruse and H. Yamamoto Tetrahedron Lett. 1988 29 1947. 200 G. Just Z. Y. Wang and L. Chan J. Org. Chem. 1988 53 1030.