9 Synthetic Methods By N.J. LAWRENCE Department of Chemistry UMIST PO Box 88 Manchester M6Q 700 UK 1 Introduction One of the year's more interesting accounts of organic synthesis may be found in John Cornforth's Robert Price lecture entitIed 'The TroubIe with Synthesis'.' He discusses the changing reasons for undertaking a synthesis and the development of organic synthesis. The recurrent theme of most papers describing synthetic methods this year has undoubtedly been catalytic asymmetric synthesis. The need for efficient asymmet- ric synthetic methods is driven in part by the pharmaceutical industry's need for enantiopure intermediates; several reviews describing chiral drugs2s3 have appeared this year. Among the most notable total syntheses of the year are those of the immunosuppressant rapamycin achieved by the groups of Ni~olaou,~ Schrieber,' and Danishefsky,6 and the synthesis of strychnine by Overman and coworkers.' An excellent behind-the-scenes account of Nicolaou's' synthesis of calicheamicin 7; has also been pubIished this year.Specialist reference works that have been published this year include Volumes 43' and 44'' of Organic Reactions which review carbonyl alkylidination using titanium reagent^,^" anion-assisted sigrnatropic rearrange- ment~,~' the Baeyer-Villager oxidation," selenoxide elimination,1ou and enone-olefin [2 + 23 photochemical cyclization.' Ob Two Tetrahedron Symposia-in-print describe synthetic methods; 'synthesis of optically active compounds -prospects for the 21st century'' and 'transition meta1 organometallics in organic synthesis'.' * Books published this year include works describing asymmetric catalysis in organic syn- J.W.Cornforth Aus. J. Chem. 1993,46 157. ' S.C. Stinson Chern. Eng. News September 27 t993 38. ' H.-J. Federsel CHEMTECH December 1993,24. K. C. Nicolaou T. K. Chakraborty A. D. Piscopio N. Minowa,and P. Bertinato,J. Am. Chem.SOC.,1993 115,4419. ' D. Romom S.D. Meyer D.D. Johnson and S. L. Schrieber J. Am. Chem. Soc. 1993 115,7906. 'C.M. Hayward D. Yohannes and S. J. Danishefsky J. Am. Chem. SOC. 1993 115,9345. 'S.D. Knight L. E. Overman and G. Paraudeau J. Am. Chem. Sac. 1993,115,9293. ' K.C.Nicolaou Angew. Chem. Int. Ed. Engl. 1993 32 1377. (a)S. H.Pine,Org. React. (N.Y,),1993,43,1; (b)S. R.Wilson ibid.1993,43,93; (c)G.R. Crow ibid. 1993 43 251. lo (a)H. J. Reich and S. Wollowitz Org. React. (N.Y.) 1993,44 1; (b) M. T. Crimmins and T. L. Reingoid ibid. 1993 44 297. *I Tetrahedron 1993,49 1711. Tetrahedron,1993 49 5415. 269 N.J. Lawrence thesis;I3 stereoselective synthesis;‘’*’ catalytic asymmetric ~ynthesis;*~*’~ chiral auxiliaries;” oxidative enzymes;” industrial chirality;*’ natural products;* ’ and stereochemistry.22 The use of enzymes in organic synthesis23 continues to be popular but is not reviewed here since it is well covered in chapter 10. 2 Carbodarbon Bond Formation The asymmetric allylation of aldehydes has been achieved in several ways.24 Keck et al. describe in a series of papers,2s the remarkably efficient allyIation of aldehydes using a catalyst derived from binaphthol and titanium tetraisopropoxide (Scheme la).0 R = PM=H 9812 (92 %) R = P+&4 303(90%) Scheme 1 Tagliavani Umani-Ronchi and coworkers report equally impressive enantioselectiv- ity when the reaction is catalysed by the BINOL-TiC1 complex.26 Tetraallyltin reacts selectively with aldehydes in the presence ofketones in aqueous acidic media (THF-aq. HCl);’’ the extremely high chemoselectivity (> 98.98 :0.02)is not observed with Lewis acids such as BF,-OEt,. Allyltrichlorosilanes add efficiently to aldehydes in DMF without cataIyst under neutral conditions; DMF is thought to coordinate to silicon to l3 R. Noyori ‘Asymmetric Catalysis in Organic Synthesis’ Wiley Chichester 1993.I’ Atta-ur-Rahman and Z. Shah ‘Stereoselective Synthesis in Organic Chemistry’ Springer-Verlag Berlin * 1993. E. Ottow and K.Schoeilkopf ‘Stereoselective Synthesis’ Springer-Verlag Berlin 1993. l6 ‘Catalytic Asymmetric Synthesis’ ed. I. Ujima VCH New York 1993. I’ H. 3runner and W. Zettlrneier ‘Handbook of Enantioselective Catalysis’ VCH New York 1993. J. Mulzer and E. Berger ‘Chiral Auxiliaries; Applications in Organic Synthesis’ Ballen Vieveg and Sohn Int. Germany 1993. l9 H. L. Holland ‘Organic Synthesis with Oxidative Enzymes’ Verlag Berlin 1993. zo ‘Chirality in Industry’ ed. A. N. CoHins Wiley Chichester 1993. z* ‘Dictionary of Natural Products’ Chapman and Hall London 1993. 22 E. Eliel and S.H. Wilen ‘Stereochemistry of Organic Chemistry’ Wiley.Chichester 1993. ” For an illustration of current research into the use of enzymes in organic synthesis see Tetrahedron Asymmetry 1993,4 Nos. 4 and 5. ’* Y.Nishigaichi A. Takuwa Y. Naruta and K. Maruyama Tetrahedron,1993,49 7395. ’’ G. E.Keck K. H. Tarbet and L. S. Geraci J.Am. Chem. Soc. 1993,115,8467; G. E. Keck and L. S. Geraci TetrahedronLert.. 1993,34,7827;G.E. Keck D. Krishnamurthy and M.C. Crier J. Org. Chem. 1993.58 6543. 26 A L. Costa M.G. Piazza E. Tagliavini C. Trombini and A. Umani-Ronchi J. Am. Chem. Suc. 1993,115 7001. ’’ A. Yanagisawa H.Inoue M. Morodome and H. Yamamoto J. Am. Chem. SOC.,1993,115 10356. Synthetic Methods 27 1 produce a hypervalent allylsilicate.28 Allylation of the chiral glyoxalate (1) is highly diastereoselective and very sensitive to the nature of the protecting changing from benzyl to triisopropylsilyl reverses the selectivity (Scheme 1b).Catalytic asymmetric cyanohydrin synthesis has received considerable attention this year.30 Corey and Whangdescribe the use of a pair of chiral catalysts (2)to activate the aldehyde and (3) to provide an equivalent of chiral cyanide ion (Scheme 2a) to achieve the asymmetric silylcyanation of aldehyde^.^ The chiraI cyanide donor is thought to be a complex formed between (3) and trace HCN. A related synthesis of cyano ethers involves the ring opening of the oxazolidinium salt (4)with sodium cyanide to give the cr-hydroxy acid (5)after quaternization and treatment with hydrochloric acid (Scheme 2b).32A more conventional synthesis of cyanohydrin derivatives has been described by de Vries and coworkers.They use the pantolactone-derived titanium complex (4)to catalyse the asymmetric silylcyanation of aldehydes with modest selectivity (Scheme 2+33 The asymmetric catalytic addition of organozinc reagents34 to aldehydes has proved as popular as ever this year (Figure 1).Some of the catalysts used include the azetidine (7),35the thiophosphorarnidate (8),36 the j3-hydroxysulfide (9),3' the hydroxyrnethyl oxazoline the diethanolamine (I 1),39 and the chromium arene complex (l2)." The study of organolanthanoid complexes has also seen great activity this year. Organocerium reagents add selectively to SAMP hydrazones (13) thereby providing an afficient route to 8-amino aldehydes and acids (Scheme 31." Similarly a-amino aldehydes are synthesized from the SAMP monohydrazone of protected gly0xa1.~~ A new method for the preparation of anhydrous lanthanoid chlorides from the metal and hexachloroethane should prove useful for the synthesis of the corresponding or- ganolanthanoid reagents.43 SeveraI groups have reported the use of chiraI ligands to control the stereochemistry of palladium-catalysed allylic substitution (Scheme 4).The groups of Helmchen Pfaltz and Williams have each used similar bidentate ligands phosphines (14),4446 sulfides (15),47 and thiophenes (16),48 which all incorporate a chirality-controlling 28 S. Kobayashi and K. Nishio Tetrahedron Lett. 1993 34,3453. 29 A. B. Charette C. Mellon L. Rouillard and E.Malenfant SYNLETT 1993 8i. 30 M.North SYNLETT 1993,807. 31 E.J.Corey and Z. Whang Tetrahedron Lett. 1993,34,4001. 32 C. Andrks M. Delgado R. Pedrosa and R. Rodriguez Tetrahedron Lett. 1993,34 8325. 33 D.Callant D.Stanssens and J.G. de Vries Tetrahedron Asymmefry 1993,4,185. 34 P.Knochei and R. D. Singer Chem. Rev. 1993,93,21 17. 35 W.Behnen T. Mehler and J. Martens Tetrahedron Asymmetry 1993,4 1413. 36 K.Soai Y.Hirose and Y. Ohno Tetrahedron Asymmetry 1993,4,1473. 37 M.C.Carreiio J. L. Garcia Ruano M. C. Maestro and L.M. Martin Cabrejas Tetrahedron Asymmetry 1993,4,727. 38 J. V.Allen C.G. Frost and J. M. J. Williams Tetrahedron Asymmetry 1993 4 649. 39 E. F.J. de Vries J. Brussee C.G. Kruse and A. van der Gen Tetrahedron Asymmetry 1993,4 1987.40 G.B. Jones and S. B. Heaton Tetrahedron Asymmetry 1993 4 261. 41 D. Enders M. Klatt and R. Funk SYNLETT 1993 226. 42 D Enders R. Funk,M. Klatt,G. raabe and E. R. Hovestreydt Angew. Chem. Int. Ed. Engl. 1993,32,418. 43 C.B.Deacon T. Feng S. Nickel €3. W. Skelton and A. H. White J. Chem. Soc. Chem. Commun. 1993 132%. 44 P.von Matt and A. Pfaltz Angew. Chem. Int. Ed. Engl. 1993 32,566. 45 J. Sprinz and G. Helmchen Tetrahedron Lett. 1993,34 1769. 46 G.J. Dawson C.G. Frost J. M.J. Williams and S. J. Coote Tetrahedron Lett. 1993,34 3149. 41 G.J. Dawson C. G.Frost C. J. Martin J. M. J. Williams,and S. J. Coote Tetrahedron Lett. I993,34,7793. 48 C.G.Frost and J. M. J. Williams Tetrahedron Lett. 1993,34 2015. N.J.Lawrence CN 88 x,$5 % m. Scheme 2 oxazoline group. Substitution of the acetate in (17) with dirnethyl malonate is impressively enantiuselective with (14) and (15) (ex. > 95%). Allylic alcohols may be used in this type of reaction by prior reaction of the allylic alkoxide with triphenyI- boron.49Zhou and P€altz50 have also used the mercaptoaryl-oxazoline (18)as a ligand for the asymmetric copper-catalysed conjugate addition of Grignard reagents to +unsaturated ketones (e.e. > 50%). Several new Lewis-acid catalysts for aldol reactions have been described. Tris(pentafl~oropheny1)boron~and lanthanum trdate5' are excellent air-stable water-tolerant Lewis-acid cataIysts fur the aldol and Michael reactions of silyl enol ethers. The methods can be used for the direct reaction of aldehydes supplied commercially as aqueous solutions (e.g.formaldehyde).On the other hand Kobayashi O9 I.Stary I.G. Stara and P. Kocovsky TetrahedronLett. t993,34 179. Q.-L. Zhou and A. Pfaltz Tetrahedron Lett. 1993 34 7725. '' K. Ishihara N.Hananki and H. Yamamoto SYNLETT 1993 577. '' S. Kobayashi I. Hachiya and T. Takahori Synthesis 1993,371. Synthetic Methods 5 mOr %; 57 86 8.e. (11) (4; (10) (9; 5 mot %; @5% e.e. (12) (A) 10 md %; El96 8.8. Figure 1 Selectivity in the addition of Et,Zn to PhCHO (33) 97 % 99 76 d.%. Scheme 3 S I 8 I Scheme 4 k k (14) X= Pph (16) (15) x=sPh (18) x=sH N. J. Lawrence and Nishio report the use of dimethyl(trifly1)silyI enol ethers as enolate equivalents for aldol and Michaef reactions without Lewis-acid catalysis.53 The asymmetric nitro- aldol reacti~n~~~~~ (Henry reaction) has been used by Shibasaki and coworkers to synthesize the /I-blocker (S)-propranolol (19) (Scheme 5).56 Scheme 5 The disclosure of new chiraI auxiliaries always generates great interest.Such is the case of a new paper from Yarnamoto and coworkers. They have found that 2,2,6,5-tetramethyI-3,5-heptanedioI(TMHDiol) derivatives such as the monobenz-oate (20) are excelIent conforrnationaIly rigid acylic chiral auxiliaries. The a,b-unsaturated ester (21) is highly selective in the conjugate addition of lithium amides [(21) 3 (22)] and Diels-Alder reactions. The high selectivity is associated with the rigid structure (21) as evidenced from X-ray and NMR analysis (Scheme 6a).Vedejs et aL5* report an interesting and highly efficient method for the alkyIation of chiral a-amino acid enolate equivalents involving transfer of chirality from starting material to product oia the transient boron complex (25) (Scheme 6b). The oxazaborolidinone (24) prepared selectiviely from the a-amidino carboxylate (23) and PhBF in situ is deprotonated and alkylated [(24) + (25)l with in most cases exceptionaI stereoselec- tivity. Symmetrical or-diones have been prepared in excellent yield by conventional reaction of organometallic reagents with the C-2 units 1,l'-oxalylimidazole59 and N,N-dimethylpipera~ine-2,3-dione.~~ Alkene Synthesik-Many important improvements to the Wittig reaction have been made this year.Vedejs et al. have shown that the phosphole-derived ethylide (26)61is extremely E selective in the reaction with both aldehydes and ketones.62 In comparison the reaction of Ph,P=CHCH exhibitsZ selectivity whilst the reaction with ketones is very much substrate dependent (Scheme 7a). Patil and Schlosser have introduced a new class of phosphorane (271 derived from tris(2-methoxymethoxy)- phosphine with enhanced cis selectivity (Scheme 8b). Stabilized ylides (X= C0,Me) 53 S. Kobayashi and K. Nishio 1.Org. Chem. 1993 58,2647. '* H. Sasai T. Suzuki,N. Itoh K. Tanaka,T. Date K. Okamura and M.Shibasaki,J. Am. Chem. SOC.,1993 115 10372. " H Sasai T. Suzuki N. Itoh S. Arai and M,Shibasaki,Tetrahedron Lett. 1993 34 2657. 56 H.Sasai N. Itoh T. Suzuki and M. Shibasaki Tetrahedron Lett. 1993,34,855. " I. Suzuki H. Kin and Y. Yamamoto J. Am. Chem. SOC. 1393 115 10139. '' E. Vedejs S.C. Fields and M. R. Schrimpf J. Am. Chem. SOC.,1993 115 11 412. '' R.H.Mitchell and V.S. lyer Tetrahedron Lert. 1993,34 3683. 6o U.T. Mueller-Westerhoff and M. Zhou Tetrahedron Lett. 1993 34 571. E. Vedejs and M.J. Peterson J. Org.Chem. 1993 58,1985. '* E. Vedejs 3. Cabaj and M.J.Peterson J. Org. Chem. 1993 58 6509. Synthetic Methods Scheme 6 show a curious solvent effect; in methanol the reaction is cis selective,whilst in hexane it is trans selective.63 When the phosphorane bears an a-heteroatom the reaction is again impressively cis selective -much more so than when a triphenylphosphine derived reagent is €:Z 22:78 with PtrJkCHCH €296:4 with(26) R2CH0 R2T (6)'-" X Scheme 7 Asymmetric Wittig reactions are proving to be popular.The chiral phosphonate (28) derived from 8-phenylmenthol reacts selectively with the meso dialdehyde (29)65to give the a,#.l-unsaturated ester (30) with the expected E selectivity (Scheme 8a). The chiral phosphonate (31) also shows high selectivity in the Horner-Wadsworth-Emmons (HWE) reaction with the meso 1,2-diketone (32) (Scheme 8b). The reaction is highly enantioselective (e.e. ;2( 100%) and somewhat surprisingly for an HWE reaction Z 63 V.Patil and M. Schlosser SYNLETT 1993 125. " X.P.Zhang and M.Schlosser Tetrahedron Lett. 1993 34,1925. 65 N.Kann and T.Rein J. Org. Chem. 1993,58,3802.I?. J. Lawrence selective.66 Chiral ketones have been kinetically resolved by HWE reaction with the phosphonate (33) derived from ~-mannitol."~ The groups of Paterson68 and Ko-skinen6' report the use of barium hydroxide and potassium carbonate in acetonitrile respectively as mild bases for the HWE reaction of Q-ketophosphonates. The modifications are particularly advantageous when base-sensitive aldehydes are used. Baldwin ef a!.have described an interesting Wittig reaction of 8-lactams; stabilized ylides react with N-Boc protected monocyclic p-lactarn~.'~ I I TBDMS I Denmark and Amburgey have reported a general stereoselective method for the synthesis of trisubstituted alkenes (Scheme 9a).7' They found that both the aikylation of the racemic fi-keto phosphonamidate (34)and subsequent reduction of the carbonyl group are highly diastereoselective.The customary base-induced HWE elimination of (35)proved problematic; however simple thermal cyc~oelirnination proceeded cleanly K. Tanaka Y. Ohta K. Fuji and T. Taga TetrahedronLett. 1993 34 4071. '' K. Narasaka E. Hidai Y. Hayashi and J.-L. Gras J. Chem. SOC.,Chem. Comun. 1993 102. 68 I. Paterson K.-S. Yeung and J. 3.SrnaIll SYNLETT 1993 774. 69 A.M. P.Koskinen and P. M. Koskinen SYNLETT 1993 501. 70 J. E. Baldwin A. J. Edwards C N. Farthing and A. T. Russell SYNLETT 1993,49. 71 S. E. Denmark and J. Amburgey J. Am. Gem. Soc. 1993,115 A0386. Synthetic Methods to give the trisubstituted alkene. Le Corre and have shown that a-metallo phosphine-boranes7 react with aldehydes in a Horner-Wittig-like manner to give E alkenes; when butyllithium is used as the base the intermediate hydroxy phosphine- borane can be isolated after work-up (Scheme9b).Most Wittig-like reactions proceed by syn elimination. However Lawrence and Muhammad have shown that Horner-Wittig intermediates (36) undergo anti elimination by reduction (LiAlH,-CeCl,) and phosphorus trichloride mediated elimination [(37) + (38)] (Scheme -ph ??% €2,955 0 It ((.) PhPiOH LiAH,,CeCI PCIa NEto -"'tC" CH,CI& rat.. 2 h =-R* R Ph R Ph Ph Scheme 9 Chiral alkenes are produced by enantioselective dehydrohalogenation of prochiral alkylbromides by chiral alkoxides derived from N-methylephedrine (Scheme 10a).75 Similarly asymmetric oxidation of the prochiral selenide (39) using Davis' chiral oxaziridine gives a reactive selenoxide (40)of undefined configuration which eliminates to the chiral alkene (41) (Scheme 10b).74 Several examples of silicon-rnediated alkene synthesis have appeared.The di-bromovinylsiktne (42) provides a useful synthon for the construction of a variety of geometrically pure alkenes. For example both bromides react with higher order cuprates to give a vinylsilane (43) that is easily desilylated with iodine in wet benzene (Scheme 1i).77Chauret and Ch~ng~~ have shown that a-epoxy(triethy1silane) serves as '' Y.Gourdel A. Ghanimi P. Pellon and M. Le Corre Tetrahedron Lett. 1993 34,1011. 73 T. Imamoto Pure and Applied 1993 65,655.74 N.J. Lawrence and F. Muhammad J. Chem. Suc. Chem. Commun. 1993 1187. 75 J. Vadecard J.-C. Plaquevent L. Duhamel and P. Duhamel J. Chem. SOC.,Chem. Commun. 1993 116. '6 €4. Komatsu S. Matsunaga T. Sugita and S. Uernura J. Am. Chem. SOC.,1993 115 5847. " R. Angell P.J. Parsons and A. Naylor SYNLETT 1993 i89. 78 D.C. Chauret and J. M.Chong Tetrahedron Lett. 1993,"34,3595. N.J. Lawrence But ph' (41) 96% 33% 8.8. Scheme 10 Scheme 11 an excellent precursor to E and 2 disubstituted alkenes by Hudrlik-Peterson chemistry. Finally Fry et al. have shown that benzal chloride (PhCHCl,) is converted to stilbene (87% E 2 1 :1.1) by the action of electrochemically generated cobalt(1) ~alen.~~ Cyc1oadditioas.-Kobayashi has shown that scandium(Ii1) triflate is an excellent catalyst for the Diels-Alder reaction." The reaction is endo selective and can be performed in both organic and aqueous media.In addition the catalyst is easily recovered and may be used at low concentrations (1mol%). Chiral Lewis acids that have been used as cataiysts for the asymmetric Diels-Alder reaction*' (Figure 2) include the copper(rr) complexes of the bis(imine) (44)82and bis(oxazo1ine) (45);83 the substituted biaryls (46)84 and (47)85 (which forms an interesting titanium(1v) helical 79 A.J. Fry U. N. Sirisoma and A.S. Lee Tetrahedron Lett. 1993 34 809. S. Kobayashi I. Hachiya M. Araki and H. Ishitani Tetrahedron Lett. 1993 34,3755. aL U. Pindur G. Lutz and C. Otto Chem. Rev. 1993 93 741. D.A. Evans T.Lectka and S. J. Miller Tetrahedron Lett. 1993 34 7027. 83 D.A. Evans S. J. Miller and T. Lectka J. Am. Chem. SOC. 1993 115,6460. 84 J. Bao W.D. Wulff and A. L. Rheingold J. Am. Chem. SOC. 1993,115,3814. 85 K.Maruoka N. Murase and H. Yamamoto 1.Org. Chem. 1993 58,2938. Synthetic Methods complex); and the 2-amino-1-indanol (48).86It0 and KatsukiS7 have used the copper(1) complex of the chiral bipyridine (49) to catalyse the asymmetric cyclopropanation of aikenes (Scheme 12). The reaction proceeds with good trans cis selectivity and excellent enantioseiectivity. (44) Figure 2 Scheme 12 Radical-based Method%-Many advances have been made this year in the use of synthetic methods that invoIve radical Ryu Sonoda and co-workers8' have shown that tris(trimethylsi1yl)silane(TTMSS) is an excellent reagent E.J. Corey T. D. Roper K. Ishihara and G. Sarakinos Tetrahedron Lett. 1993 34 8399. 87 K.Ito and T. Katsuki Tetrahedron Lett. 1993 34 2661. P. Dowd and W. Zhang Chem. Rev. 1993 93 2091. 89 1. Ryu M. Hasegawa A. Kurihara A. Ogawa S. Tsunoi and N.Sonoda SYNLETT 1993 143. N. J. Lawrence for the free-radical formylation of alkyf halides (Scheme 13). Additionaly when an electron-deficient alkene is present unsymmetrical ketones (50)are produced. TTMSS is superior to tin hydrides for this purpose due to its modest ability to donate a hydrogen atom to both the intermediate alkyl and acyl radical. TTMSS also effects the isomerization of some 2 alkenes to their E isomers by an addition-elimination path~ay.~' Finally tributylstannyl radicals may be generated in the absence of tin hydride species by mild photochemical methods employing acetone as a triplet ~ensitizer,~' or by thermal decomposition of 0,O'-bistributyItin benz~pinacolate.~~ 3 Reduction Oxazaborolidine catalysts have seen widespread use for the reduction of ketones [(Sl) + (5211 (Scheme 14).New oxazaborolidine catalysts introduced this year include the phenylglycine-derived (53),93 the hydroxysulfoximine (54),94 and the erythro 2-amino-1,2-diphenylethanol derived (55).95 Interestingly the complex (56) derived in situ from the corresponding amino alcohol behaves in the same way as the alkyIated complex (55);96the method therefore avoids the potentially troublesome isolation of the oxazaborolidine.Liotta and coworkers have published the results of a theroreticaf study of such oxazaborolidine-catalysed ketone reductions and suggest that hydride transfer occurs via a chair-like transition state (58) in contrast to the previously proposed boat transition state (57) (Scheme 15).97It has also been shown that the use of oxazaborolidine-borane complexes in combination with triethylamine leads to increased levels of enantioselectivity. The origins of this curious effect are not entirely clear although it appears the amine might trap the initial monoaIkoxyborane which itself may show lower selectivity than the oxazaborolidinone-borane complex.9B Evans ef al. report a highly efficient asymmetric version of the Meer-wein-Pondorf-Verley (MPV) reduction [(SS) + (60)] (Scheme 16).They found that the samarium complex (61)? obtained from samarium(Ir1) iodide and a styrene-oxide-derived tridentate ligand catalyses the hydrogen transfer from isopropanol to a range '* C. Ferreri M. BaIlestri and C. Chatgilialoglu TetrahedronLett. 1993,34,5147. 91 M. Harendza J. Junggebauer K. Lessrnann W. P.Neumann and H. Tews SYNLETT 1993,286. 92 M.J. Tomaszewski and J. Warkentin J. Chern. Soc. Chern. Commun. 1993 1407. 93 C.Dauelsberg and 3. Martens Synth. Comun. 1993,23,2091. "C.Bolm and M. Felder TetrahedronLett. 1993,34,6041. 95 G.J. Quallich and T. M. Woodall Tetrahedron Lett. 1993,34,4145. 96 G.J. Qualljch and T. M.WoodalI SYNLETT 1993,929. 97 D.K.Jones D. C. Liotta I. Shinkai and D.J. Mathrt J. Urg. Chem. 1993,58 799. 98 D.Cai D. Tschaen Y.-J. Shi T.R.Verhoeven R.A. Reamer and A. W. Douglas Tetrahedron Lett. 1993 34.3243. Synthetic Methods 28 1 0 I! HO 1 3H3*THF catalyst (53)88 % e.e.,2 mol % (S) (54) 76 % 8.8.-10md % (R) (55) R = Me 94 % ee (56) R=H94%ee Scheme 14 (57) Scheme 15 of aromatic ketone^.^' The chiral ruthenium and rhodium complexes (62)loo and (63)"' have also been used in a similar manner to obtain moderate selectivity. Molander and McKie report the highly stereoselective samarium(IxI)-catalysed intramolecular MPV reaction. lo2 Other modified MPV catalysts include silica gel-supported zirconi~rn(iv)~~~ fur the reduction of carboxyhc and zir~onia/titania'*~ acids and sterically hindered ketones.The year has seen significant developments in the area ofasymmetric hydrogenation reactions. Buchwald and coworkers have used the titanocene catalyst (64) to achieve the asymmetric hydrogenation of unfunctionalized trisubstituted alkenes (Scheme 17a).lo5Prior to this disclosure only alkenes that possessed a chelating substituent could successfulIy be reduced stereoselectively . The same catalyst has been used to reduce cyclic irnines to the corresponding cyclic amine.Io6 Faller and Parr have 99 D. A. Evans S.G. Nelson M. R. Gagne and A. R.Muci J. Am. Chem. SOC. 1993,115,9800. loo J.-P. Genet V. Ratovelornanana-Vidal and C. Pinel SYNLETT 1993 34 478. lo' P. Gamez F. Fache P. Mageney and M. Lernaire Tetrahedron Lett. 1993 34 6897. G.A.Molander and J.A. McKie J. Am. Chem. Soc. 1993 115 5821. Io3 K. Inada M. Shibagaki Y. Nakanishi and H. Matsushita Chem Lett. 1993 1795. Io4 K. Takahasi M. Shibagaki H. Kuno and H. Matsushita Chem. Lett. 1993 839. Io5 R. D. Broene and S. L. Buchwald J. Am. Chem. SOC. 1993 115 12569. lo6 C.A. Willoughby and S. L. Buchwald J. Org. Chem. 1393 58 7627. N. J. Lawrence (60)96% 97% 8.8. with (61) 80%. 52% e.e.(S)with (62) 67% 9.8. with (s3) Scheme 16 introduced the concept of chiral poisoning as a new strategy for asymmetric cataiysis (Scheme 17b).'*' This is especially useful when the catalyst is expensive [such as chiraphos (6511 and the poison cheap. The principal is illustrated by the reduction of alkenes with the racemic chiraphos rhodium complex (66).Addition of the S isomer of the thiophosphinite (57) results in selective poisoning of the (S,S)-chiraphos species. Faller has also applied the same principle to the kinetic resolution of allylic alcohols by selectively reducing one alkene with a poisoned ruthenium catalyst.'" Cycloalkanones are reduced with impressive enantioselectivity ( >90% e.e.) by hydrogenation using iridium(1) BINAP catalysts in the presence of bis(o-N,N- dirnethy1aminophenyl)phenylphosphine. log The (R)-BICHEP-Ru(ir) complex (68)is also an excellent catalyst for the enantioselective hydrogenation of a-ketoamides (69) (Scheme IXa)."O Asymmetric hydrosilylation of ketones [(TO) + (7f)l is achieved with high enantioselectivity with the new chiral bipyridine Bipymox (72) (Scheme 18b),' and TADDOL-derived cyclic phosphonites and phosphites.' ' Reduction with complex hydride reagents is the subject of many reports.Carboxylic acids are conveniently reduced to aldehydes in a one-pot procedure with piperidine and sodium diethyldihydroaluminate. ' Singaram's newly reported lithium aluminium hydride equivalent lithium pyrrolidinoborohydride is highly regiospecific in a 1,2 sensein the reduction of a$-unsaturated ketones.' The same reagent reduces tertiary arnidesto the corresponding alcohol. * ' Reduction of esters' and acid chlorides' ' is lo' 1.W. Faller and J. Parr J. Am. Chem. Soc. 1993 115 804. lo8 J.W. FaIler and M. Tokunaga Tetrahedron Lett. I993,34 7359. lo9 X. Zhang T.Taketomi T. Yoshizumi H.Kumobayashi S.Akutagawa K. Mashima and H. Takaya J. Am. Chem. Soc. 1993 115 3318. 'lo T. Chiba A. Miyashita H. Nohira and H. Takaya Tetrahedron Lett. 1993 34 2351. 'I1 H. Nishiyama S. Yarnaguchi S.-B. Park and K. Itoh Tetrahedron Asymmetry 1993 4 143. 'I2 J.-i. Sakaki W.B. Schweizer and D. Seebach Helv. Chim.Acta 1993 76 2654. N.M. Yoon,K.I. Choi Y.S. Gyoung and W. S. Jun Synth. Commun. 1993 23 1775. .I.C. Fuller E. L. Stangeland C.T. Goralski and B. Singaram Tetrahedron Lett. 1993-34 257. 'I5 G. B. Fisher,3. C. Fuller J. Harrison C.T. Goralski and B. Singaram Tetrahedron Lett. 1993,34,1091. N. M. Yoon,J. H. Ghn D. K. An and Y.S. Shon 1.Org. Chem. 1993,58 1941. I" J.S. Cha and H.C. Brown J. Org.Chem. 1993,58,4732. Synthetic Methods t 1 79 % 95 % 8.8.(64) R = (R,R)-l,l'-biiaphth-2.2'-didate Scheme 17 achieved with sodium diethylpiperidinylafurninohydride and sodium tris-t-butoxyalurninohydride respectively. Esters carboxylic acids amides and nitriles are efficiently reduced with samarium diiodide in the presence of water."* Secondary amides are reductively deoxygenated by Scbwartz's reagent (Cp,ZrHCi) to the corresponding imine.' l9 Alcohols are reduced to alkanes12' by the action of sodium borohydride and the phosphonium anhydride reagent (Ph3P+)20(CF,S0,12. a-Amino acids are conveniently reduced without racernization to the corresponding amino alcoholby sodium borohydride and iodine.' ' Miscellaneous reagents fur the reduction of ketones include copper(1r)- exchanged-cation resin-NaBH and lithium trisf( 3-t-but yl-3-pentyl)oxy] aluminium hydride.l2'9' 118 Y.Kamochi and T. Kudo Chem. Lett. 1993 1495. D. J. A. SchedIer A. G. Godfrey and 3. Ganem Tetrahedron Lett. 1993 115 5035. J. B. Hendrickson M. Singer and M. S. Hussoin J. Org. Chem. 1993 58,6913. M.J. McKennon A.I. Meyers K.Drauz and M. Schwarm J. Org. Chem. 1993 58 3568. 122 A. Sarkar B.R.Rao,and 8. Ram Synth. Commun. 1993 23 291. G. Boireau A. Weberly and R.Toneva SYNLETT 1993 585. N.J.Lawrence 0 Scheme 18 4 Oxidation Oxidation is the subject of issue 164 of Topics in Current Chen~istry;’’~ peroxygen reagents,lZ4’ di~xiranes,”~~ and catalytic oxidation enantioselective ep~xidation,’~~~ with peroxide reagents’ 24d are reviewed. Sharpless and coworkers continue their pioneering studies of asymmetric dihydroxylation of alkenes.The osmium-catalysed asymmetric dihydroxylation of terminal alkenes is efficiently achieved by use of the pyrirnidine-Iinked ligand (DHQD),-PYR (73),’ 25 or (DHQD),-PHAL (74);’26for this type of aIkene the new ligands are superior to the previously described phthalazine catalysts whose preparation has been recently described. ”The asymmetric dihy- droxylation of tetrasubstituted double bonds occurs with low to very high enan- tioselectivity with both phthalazine and pyrimidine ligand classes. 12’ Among other substrates treated with AD-mixes are a-substituted styrenes and a-phenylacrylates,’ 29 a,P-unsaturated ketones,’ 30 a#-and &+unsaturated arnides,’” aryl ally1 allyldanes ’3371 34 and tertiary alIylic alcohols.‘35 The procedure has seen several uses lZ4 (a) H.Heaney Top.Curr. Chem. 1993,164 I ;(b)W. Adam and L. HadjiarapogIou,ibid. 1993,164,45; (c) E Hoft ibid. 1993 164 63; (d) R. Sheldon ibid. 1993 164 21. G.A. Crkpino K.-S.Jeong H. C. Koib Z.-M. Wang D. Xu and K. B. Sharpless,J. Org. Chem. 1993,58 3785. 126 M. P. Arrington Y.L. Bennani T. Gobel P. Walsh S.-H. Zhao and K. 8. Sharpless Tetrahedron Lerr. 1993,34 7375. W. Amberg Y.L. Bennani R. K. Chadha G.A. Crispino,W. 13.Davis J. Hartung.K.4. Jeong Y. Ogino T. Shibata and K. 8. Sharpless J. Org. Chem. t993 58 844. K. Morikawa J. Park P. G. Andersson T. Hashiyarna and K. B. Sharpless,J. Am. Chem.Suc. 1993,115 8463. Z.-M. Wang and K. B. Sharpless SYNLETT 1993 603. I3O P.J. Walsh and K.B. Sharpless SYNLETT 1993 605. 13’ Y.L. Bennani and K. B. Sharpless Tetrahedron Lett. 1993 34 2079. Z.-M. Wang X.-L. Zhang and K. B. Sharpless Tetrahedron Lett. 1993,34 2267. 13’ S. Okamoto K. Tani F. Sato K. 3.Sharpless and D. Zargarian Tetrahedron Lett. 1993 34 2509. ’34 J.A. Soderquist A.M. Rane and C. J. Lopez,Tetrahedron Lett. 1993 34 1893. 13’ Z.-M. Wang and K. B. Sharpless Tetrahedron Lett. 1993 34 8225. Synthetic Methods in natural product synthesis. 36-1 39 Not surprisingly asymmetric dihydroxylation may be used to resolve racemic oIefins kineticalIy;there being a 30-fold difference in the rate of reaction of each enantiomer with AD-mix a [containing (DHQ),-PHAL] and AD-mix #? [containing (DHQD),-PHAL] (Scheme l!J).'40Similarly secondary allylic acetates may be kinetically resolved using the teraphthalyl linked ligand (75).14' Corey's and Sharpless' groups have sought to explain the origin of the high enantioselectivity. Corey argues that the reaction proceeds via a p-0x0-bridged bisOsfvn~) species Q0,0s[O,]OsO,Q. 14' However the conclusion from the Sharp- less group is different; they believe that the two quinuclidine units do not act in concert tie. the active species is a 1:1 Os0,-phthalazine Iigand DHQD (R = Me} DHQD' (R = 'pentyl) Scheme 19 136 G.A. Cnspino and K.B. Sharpless SYNLETT 1993,47. 13' G. A. Crispino and K.B.Sharpless Synthesis 1993,777. 13' H.C.Kolb Y. L. Bennani and K. B. Sharpless Tetrahedron Asymmetry 1993 4 133. 139 Y.L. Bennani and K.B. Sharpless Tetrahedron Lecr. 1993,34 2083. M.S.VanNieuwenhze and K. B. Sharpless J. Ant. Chem. SOC. 1993,115 7864. 141 B. B. Lohray and V. Bhushan Tetrahedron Lett. 1993,34 3911. E. J. Corey M. C. Noe and S. Sarshar J. Am. Chem. Soc. 1993,115,3828; E. J. Carey and M. C. Noe J. Am. Chem. Soc. 1993 115 12579. H. C. Kolb P.G. Andersson Y. L. Bennani G.A. Crispino K.-S. Jeong H.-L. Kwong and K. B. SharpIess,J.Am. Chem.Soc. 1993,115,12 226;T. Giibel and K. B. Sharpless,Angew. Chem. Int. Ed. Engl. 1993 32 1329. N.J. Lawrence Hanessian et al. have used the readily available C symmetric 1,2-diamine (76) to control the enantioselectivity of osmium tetroxide mediated dihydroxylation of a wide range of alkenes (Scheme 2Oa). Although the enantioselectivities are impressive at present stoichiometric amounts of osmium and amine are required.'44 Henry and Weinreb report a useful method for the oxidative cleavage of alkenes C(77) -, (78)] with catalytic osmium tetroxide and excess Jones' reagent (Scheme 2Ub).145 Similarly alkenes are oxidatively cIeaved to aldehydes by the action of potassium permanganate supported on alumina -yields are good and the conditions mild."' Scheme 20 Many new reagents have been developed for the oxidation of alcohols.Allylic alcohols are selectively oxidized in the presence of primary alcohols with stoichiomet- ric palladium(I1) salts;147 this may prove more useful when a catalytic version is developed. Aerobic oxidation with metal catalysts is attractive for economic and environmental reasons.For example simple secondary alkyl alcohols are oxidized by molecular oxygen with a ruthium(r~~~obalt(~i) bimetallic catalyst. 148 Molecular oxygen has also been used in the Baeyer-Villiger oxidation of ketones to lactones in the presence of benzaldehyde with or without metal [CU(II)or Ni(~r)]catalysis.'49 Other reagents for the oxidation of alcohols include Mn0,-bentonite-microwave;' 50 trichloromelarnine;'51 hypochlorous acid in methanol (to yield esters directly from CrO (cat.F70% aq. B~t00H;~~~ primary alcohol~);'~~ chrornium-substituted aluminophosphate-5 zeolite-Bu'OOH; s4 and the complex HUF-CH,CN. 55 The S. Hanessian P.Meffre M. Girard S. Beaudoin J.-Y. Sanceau and Y.Bennani J. Org. Chem. 1993,58 1991. I*' J.R.Henry and S. M. Weinreb J. Org. Chem. 1993 58 4745. D.G. Lee T. Chen and Z. Wang J. Org.Chem. 1993 58 2918. V. Bellosta R. Benhaddou and S. Czernecki SYNLETT 1993 861. 14* S.-I. Murahashi T.Naota and N. Hirai J Org.Chem. 1993 58 7318. 149 C. Bolm G. Schlingloff and K. Weickhardt Tetrahedron Lett. 1993 34 3405. Is* L. A. Martinez 0.Garcia F. Delgadc C. AIvarez and R. Patiiio Tetrahedron Lett. 1993 34,5293. S. Kondo M. Ohira S. Kawasoe H. Kunisada and Y. Yuki,J. Org. Chem. 1993 58 5003. C. E. McDonald L. E. Nice A. W. Shaw and N. B. Nestor Tetrahedron Len.,1993 34 2741. J. Muzart and A. N'Ait Aijou Synthesis 1993 785. J.D. Chen J. Dakka E. Neeleman and R. A. Sheldon J. Chem. Soc. Chem. Commun. 1993 1379. S. Rozen Y. Bareket and M.Kol Tetrahedron 1993 49 8169. Synthetic Methods 287 Dess-Martin periodinane a useful reagent for the oxidation of alcohols has seen an improved and large-scale synthesis. Aromatic aldehydes are oxidized efficiently to the corresponding benzoic acid with hydrogen peroxide in formic Epoxidation continues to draw much attention. Iqbal and coworkers have found that the epoxidation of alkenes with molecular oxygen is achieved using the hydroperoxide(79),derived by in situ cobalt(I1)-catalysed autoxidation of (80)(Scheme 21a).158 Schwenkreis and Berkessel have used the manganese(Ir1) complex (81) of the dihydrosalen Iigand bearing a pendant imidazole group as a biomimetic catalyst for epoxidation of alkene~."~ Collman et al.160 have similarly used a threitoktrapped manganese porphyrin as an epoxidation catalyst; oxidation of 1,2-dihydronaphtha- lene (82) is highly enantioselective (88% e.e.).Katsuki and coworkers have used the dihydrosalen catalyst (83) bearing axially chiral binaphthyl groups to oxidize the same alkene (Scheme 21b).16' Komiya and coworkers also report the epoxidation of alkenes with molecular oxygen and catalytic copper(I1) salts; however the reaction is not stereospecific.'62 Other reagents for epoxidation include bis(ephedrine)cobalt~I~~~~;1",'54 clay-impregnated-wit h-Ni (11 b02 and is0 bu tyraldehyde;'6s and pol ymer-supported Mn(IIr)-salen compfexes and iodosylbenzene. Mukaiyarna et a/.have reported the use of propionaldehyde diethyl acetal as a reductant in the cobalt(i1)-catalysed aerobic epoxidation of afkenes.'67 The method is neutral and can be used to synthesize acid-sensitive epoxides.168 A different approach to catalytic epoxidation has been taken by Manoury et LZ~.;'~~ the tartrate-derived borate (84)catalyses oxygen transfer from t-bu tylhydroperoxide to prochiral alkenes with moderate enan tioselectivity (Scheme 22a).Chiral epoxides are obtained in moderate enantiomeric excess from racemates by chiral Lewis-acid catalysed ring-opening with diethylamine (Scheme 22b).170 Terminal epoxides are efficiently constructed in a two-step process from chiral trichloromethykarbinals (accessible by oxazaborolidine reduction of the ketone) by selective reduction and base-catalysed ring closure of the resulting chlorohydrin.17' Hindered alkenes are efficiently epoxidized with nitrogen dioxide.l" Epoxides are also synthesized by a modification of Corey's reaction of carbonyl compounds and sulfonium ylides by generation of the sulfoniurn ylide in situ from dimethyl sulfide methanol and sulfuric acid.' 73 Epoxides are converted directly into carboxylic acids 15' R. E. Ireland and L. Liu J. Org. Chem. 1993 58,2899. 157 R. H. Dodd and M. Le Hyaric Synthesis 1993 295. T. Punniyamurthy B. Bhatia and J. Iqbal Tetrahedron tert. 1993,34 4657. T. Schwenkreis and A. Berkesset Tetrahedron Lett. 1993 34 4785. J. P. Collman V.J. Lee X. Zhang J. A. Ibers and J.I. Brauman J. Am. Chem. Sor. 1993 115 3834. 16' H. Sasaki R. Irie and T. Katsuki S YNLETT 1993,300; for other compkxes see N.Hosoya R. Irie and T. Katsuki S YNLETT I993 261. S.4. Murahashi Y. Oda T. Naota and N. Korniya J. Chem. SOC. Chem. Commun. 1993 139. 163 I. Iqbal S. Bhatia and M.M. Reddy Synth. Commun. i993 23 2285. S. Bhatia T. Punniyamurthy B. Bhatia and J. Iqbal Tetrahedron 1993 49 6101. E. Bouhlel P. Laszlo M. Levart M.-T. Montaufier and G. P. Singh Tetrahedron Lett. I993,34,1123; P. Laszlo and M.Jxvart Tetrahedron Lett. 1993 34 1127. B. 3.De B. B. Lohray and P.K. Dhal Tetrahedron Lett. 1993 34 2371. 16' T. Mukaiyama K. Yorozu T. Takai and T. Yamada Chem. Lett. 1993,439. 168 K. Yorozu T. Takai T. Yamada and T. Mukaiyarna Chem. Lett. 1993 1579. 169 E. Manoury B. A. H. Mouloud and G.G.A. Balavoine Tetrahedron Asymmetry 1993 4 2339. 170 M. Brunner L. Mussmann and D.Vogt SYNLETT 1993 893. E. J. Corey and C.J. Helal Tetrahedron Lett. 1993 34 5227. 172 E. Bosch and J. K. Kochi J. Chem. Soc. Chem. Comrnun. 1993,667. 173 J. Forrester R. V. H.Jones P. N. Preston and E. S.C.Simpson J. Chem. Soc. Perkin Trans. 1,1993,1937. N.J. Lawrence (82) 72 % 64 % e.8. 7? % 86 % 8.8.. a. w2h (83)(2.5 d%) PhD pwine N -0-But-Scheme 21 by the action of bismuth(II1) mandelate; olefins and alcohoIs are tolerated by the reagent (Scheme 23).174 New methods for the asymmetric aziridination of alkenes continue to be developed. Jacobsen and coworkers report the use ofthe copper(1) complexes of the chiral Schiff base (85) to catalyse the aziridination of alkenes with the iodinane (85) (Scheme 24a);' 75 aziridination of chromene derivatives is particularly efficient.Katsuki and coworkers have also used the manganese-salen catalyst in a similar manner to achieve asymmetric aziridination with moderate selectivity in the best case.' 76 Similarly Evans et al. report the chiral aziridination of phenyl cinnamate with the copper complex of the bis(oxazo1ine)(87) (Scheme 24b).'77 N-hydroxy-N-pivaluylanilinehas also been used for the aziridination of a1kenes.l78 Sulfides are oxidized selectively to sulfoxides with the peracetoxyimidic acid T. Zevaco E. Duiiach and M. Postel Tetrahedron Lett. 1993 34,2601. Ii5 Z. Li K.R.Conser and E. N. Jacobsen J. Am. CAem. SOC.,1993,115 5326. K. Noda N. Hosoya R. Irie Y. Ito and T. Katsuki SYNLETT 1993,469. 177 D. A. Evans M. M.Fad M.T. Bilodeau B. A. Anderson and D. M. Barnes J. Am. Chem. Soc. 1993,115 5328. 17' M. M. Pereira P. P,U. Santos L.V. Reis A. M. Lobo and S. Prabhakar. J. Chem. Soc. Chem. Commun. 1993,38. Synthetic Methods 75 % 8.8. 52 % 0.8. Scheme 22 BII#l)+~mndeietef 10 mo! %) RCOZH DMSO 80 "C Scheme 23 .. 75% >98 % e.e. 61% 97 % 6.8. (87) Scheme 24 generatedin situ from acetonitriIe and hydrogen peroxide;'79 a similar transformation is affected by photolysis in the presence of tetranitromethane.18* Tetrapropylarnmon- ium perruthenate is an efficient catalyst for the oxidation of sulfides to sulfones.18' Sulfoxidesare kinetically resolved by titanium-binaph thol-mediated oxidation of one enantiomer to the sulfune. 82 P.C.Bulrnan Page A.E. Graham D. Bethell and K. B. Park Synth. Commvn. 1993,23,1507 D. Ramkumar and S. Sankarararnan Synthesis 1993 1057. 18' K. R. Guertin and A. S. Kende Tetrahedron Lett. 1993,34,5369. lBz N. Komatsu M. Hashizume T. Sugita and S. Uemura J. Org. Chem. 1993 58,7624. N.J. Lawrence 5 Protection Protecting group methodology has seen much study this year. The use of silyl ethers as protecting groups especially in conjunction with oxidation reactions has been reviewed.ls3 Primary and secondary alcohols are rapidly protected as their t- butyldiphenylsilyl ethers by the action of t-butyldiphenylsiiyl chloride and ammonium nitrate or perchlorate,' 84 and as their trimethylsilyt ethers with hexamethyldisilazane and zinc chloride.* 85 Lipshutz et a!.' 86 report the use of trimethylsilylfuorosulfonate (TMSOFS) as a cheap alternative to trimethylsiiyl triflate for the protection of sterically hindered alcohols. The TMSOFS is simply prepared in situ by protodesilyl- ation of allyltrimethylsilane with fiuorosulfonic acid. SeveraI methods fur the deprotection of allyl-protected amines and alcohols have appeared. AlIyl glycosides are deprotected by conversion into the 2-oxopropyl glycoside by Wacker oxidation [Pd(ri),Cu") O,] followed by photofysis.lS7 Ally1 and I-propenyl ethers are deprotected in a similar fashion [Pd(ri) CU~I), H,U,] but without recuurse to photolysis.ls8 AIiyI ethers and amines are deprotected by in situ generated dicyclopentadienyl zirconium (Cp,Zr);' 89 tetrahydropyranyl ethers diiso- propylidene acetals and esters (partially) are tolerated by this reagent.Allylamines are also rapidly deprotected by palIadium(o) allylic substitution with N,N'-dimethylbar- bituric acid.'" Propargylic ethers are selectively cleaved to the correspondingalcohol with low-valent titanium (TiCIJMg) in the presence of silyl benzyl and methyl ethers. 91 BenzyI-protected alcohols are seiectively deprotected in the presence of t-butyIdiphenylsily1 ethers by boron-trichloride-dimethyl-sulfide Tet-rahydropyranyl ethers are efficiently made from dihydropyran with catalytic [Ru(CH,CN),(triphos)30 [triphos = CH,C(CH2PPh,),].'93 Tetrahydro-pyranyl ethers are also formed by molybdenum(v1) acetyla~etonate,'~~ ceric am- monium nitrate,"' or H-Y zeolite'96 and 3,4-dihydro-2H-pyran.AIcohoIs are protected as their 2-tetrahydrofuranyl ethers by n-tetrabutyIammonium-peroxydisul-fate-mediated radical coupling with tetrahydr~furan.'~~ DimethoxytrityI-protected alcohols and thiols are selectively deprotected in the same molecule by 80% acetic acid (as.) and silver nitrate4ithioerythrito1 re~pectively.'~' Both 1,2 and 1,3-diols are rapidly and efficiently protected as their base-labile cyclic carbonates by reaction with triphosgene."' BOC-protected amides are selectively deprotected with catalytic J. Muzart Chem. Rev. I993,93 11. 18* S.A. Hatdinger and N. Wijaya Tetrahedron Lett. 1993 34 3821. H. Firouzabadi and B. Karimi Synth. Commun. 1993 23 1633. IB63.H. Lipshutz J. Burgess-Henry and G.P.Roth Tetrahedron Lett. 1993 34,995. I*' J. Liinning U. Moller N. Debski and P.Welzel Tetrahedron Letr. 1993 34 5871. IB8H. 3. Mereyala and S. Guntha Tetrahedron Lett. 1993,34 6929. €I. Ito T. Taguchi and Y.Hanzawa J. Org. Chem. 1993,58 774. 190 F. Garro-Helion A. Merzouk and F. Guibk J. Org. Chem. 1993 58,6109. 19' S.K. Nayak S.M. Kadam and A. Banerji SYNLETT 1993 581. 19' M.S. Congreve E.C. Davison M.A. M. Fuhry A. B. Holmes A. N. Payne R.A. Robinson and S. E. Ward SYNLETT 1993 663. 193 S. Ma and L. M. Venanzi Tetrahedron Lett. 1993,34 5269. 194 M. L. Kantarn and P. L. Santhi Synth. Comun. 1993 23 2225. 195 G. Maity and S.C. Roy Sy~th.Commun. 1993 23 1667. 196 P. Kumar C. U. Dinesh R.S. Reddy and B. Pandey Synthesis 1993 1069. J.C. Jung H.C.Choi and Y. H. Kim Terrahedron Lerr. 1993 34,3581. 198 Z. Huang and S. A. Benner SYNLETT 1993,83. 199 R. M. Burk and M. B. Roof Tetrahedron Lett. 1993 34 395. Synthetic Methods 29 1 rnagnesium(1r) perchlorate in acetonitrile even in the presence of BOC-protected amines.’ O0 Esters are often used to protect alcohols and several new methods for their synthesis and hydrolysis’” have been described. Vedejs eta!.report the use of tributylphosphine as a remarkable catalyst for the acetylation and benzoylation of alcohols.202 In the latter case tributyiphosphine is a more efficient catalyst than the well-documented acylation catalyst DMAP. The use of bulky amines (PriEtN or 1,2,2,6,6-pentamethyI- piperidine) with acetyl chloride (-78 “C r.t.) results in the selective acylation of primary alcohofs in the presence of secondary alcohols (>99.6 :0.4).203Folmer and Weinreb204 report a potentially useful and mild one-pot method for ester synthesis involving activation of carboxyk acids with AppeI’s salt (88)to acyl- 1,2,3-dithiazoles (89) (Scheme 25).Formate esters are efficiently made from alcohols with thionyi Scheme 25 chioride-DMF-lithium iodide; when potassium iodide is used the corresponding alkyl iodide is i~olated.”~ Another simple procedure for the formylation of alcohols and amines by reaction with cyanomethylformate is described.206 The deprotection of acetate and pivaloy1 esters is achieved rapidly (in just a few minutes) by microwave promoted hydrolysis on Similarly t-butyldimethyisityl ethers,208 benzal- dehyde diacetate~,~” acetates,’ lo and benzyl ethers’ are deprotected by microwave promoted hydrolysis on alumina.The procedures involve no reaction solvent and minimal work up. Several new methods for the removal of acetal protecting groups have been reported. Thioacetals and thioketals are deprotected photochemically (2 > 350 nm) in the presence of 2,3-dichloro-5,6-dicyano-p-benzoquinone (DDQ);alternatively the same transformation is achieved thermally by heating in acetonitrile under reflux.’’2 Node ‘O0 J. A. Stafford M. F. Brackeen D.S. Karanewsky and N. L. Valvano Tetrahedron Lerr. 1993,34,7873. ’O‘ C. J. Salomon E.G. Mata and 0.A. Mascaretti Tetrahedron 1993 49. 3691. ’02 E. Vedejs and S.T. Diver 3. Am. Chem.SOC.,1993 115,3358; E. Vedejs N. S. Bennet. L. M. Conn S.T. Diver M. Gingras S. Lin P. A. Oliver and M.J. Peterson J. Org. Chem. 1993 58 7286. ’03 K. Ishihara H. Kurihara and W. Yamamoto J. Ory. Chem. 1993 58 3791. ”* J.J. Folrner and S. M. Weinreb Terruhedron Lett. 1993 34 2737. ’05 I. Fernandez B. Garcia S. Muiioz J. R. Pedro and R.de la Salud SYNLBTT. 1993. 489. lo6 J. Deutsch and H.-3. Niclas Synth. Commun. 1993 23 1561. ’07 S.V.Ley and D.M. Mynett. SYNLETT 1993 793. ’08 R.S. Varma J. B. Lamture and M. Varma Tetrahedron Left. 1993 34 3029. ’09 R.S. Varma A. K. Chatterjee and M. Varma Tetrahedron Lett. 1993,34 3207. ”* R.S.Varrna M. Varma and A. K. Chatterjee J. Chem. Soc. Perkin Trans. 1 1993 999. ’” R.S. Varma A. K. Chatterjee and M. Varma Tetrahedron Lerr.1993 34 4603. ”’L. Mathew and S. Sankararaman J. Or$.Chem..1993 58 7576. N.J. Lawrence et 01.'~~have developed a reagent system (silver nitrate-iodine) for the rapid and mild deprotection of both dithioacetal and monothioacetal groups. Dithioacetals are efficiently hydrolysed by the electrophilic fluorinating reagent N-fluoro-2,4,6-trimethylpyridiniurn triflate in aqueous TNF.214Roskamp and Ford report an improvement for the deprotection of acetals with ti@) chloride; the rate of hydrolysis is greatly increased by simply adding catalytic naphthalene or remarkably C,,.21 On occasions in a synthesis it is necessary to change protecting groups to circumvent incompatibilityproblems. Efficient one-pot procedures are desirable for this purpose.To this end benzyl-protected alcohols are efficiently converted into their correspond- ing acetates by the action of catalytic tin@) bromide and acetyl bromide.216 Similarly amine protecting groups may be changed; N"-fluorenyirnethoxycarbonyl(Fmoc) groups are converted into an Nu-benzyloxycarbonyl (Z) group by potassium fluoride and N-benzyloxycarbonyl-5-norbornene-2,3-di~arboximide (BCN).'17 6 Miscellaneous Preparations Chiral acylations are normally best carried out by the use ofenzymes. However many workers are developing reagents and catalysts to effect this process. Evans and coworkers2" have used the imide (90)as a chiral acyhting agent to resolve secondary alcohols kinetically (Scheme 26a). Kinetic selectivity of 213-30:1 for the R enantiomer of the magnesium alkoxide is observed.Katsuki and co-workersZfg have used the chiral benzirnidazole (91) for the chiral acylation of lithium amide-enolates (Scheme 26b). Scheme 26 213 K. Nishide K. Yokota D. Nakarnnra T. Sumiya M. Node M. Ueda and K. Fuji Tetrahedron Len. 1993,34,3425. A.S. Kiselyov L. Strekowski and V.V. Semenov Tetrahedron Lett. 1993 49 215i. 'IS K.L. Ford and E.J. Roskamp J. Org. Chem. 1993,58,4142. T. Oriyama M.Kimura M. Oda and G. Koga SYNLETT 1993,437. ''' W.-R. Ei 3. Jiang and M. M. Jouilik SYNLETT 1993 362. 218 D.A. Evans J.C. Anderson and M. K. Taylor Terrahedron Lett. 1993,34 5543. 'I9 M. Ogata T. Yoshimura H. Fujii Y. Ito and T. Katsuki SYNLETT 1993 728. Synthetic Methods Several reports describe the development of reagents that are chira1 proton equivalents for the protonation of prochiral nudeophiles.Amines have rarely been used as the source of chiral protons for the enantioselective protonation of prochiral enolates [(94) -+ (9511 (Scheme27). However,the groups of Fuji"" and KogaZ2l have reported the use of the piperazine (92)and the triamine (93)respectively as reagents fur the stereoselective protonation of lithium enolates. @ h. &7wa033Pm -&.,,t),,,j":,"c bh (W (95) (92) Scheme 27 Davies et al. have continued to illustrate the usefulness of the enantioselective conjugate addition of (a-methy1benzyl)benzylamineto t-butyl cinnarnate by applica-tion to the syntheses of or-methyl-~-phenylaianines,222 the taxol-side chain,223 and cis-pen tach224 Perhaps just as important as asymmetric synthetic methods are the methods for the exact determination of enantiomeric excess Accordingly Feringa and coworkers have developedthe phosphoric acid chloride (96)for the determination of the optical purity ofchiral akohols and amines by "P NMR spectroscopy.225An interesting account of the accurate determination of extremely high enantiomeric purity appears in a paper by Rautenstrauch et ~1.~'~ The principles are applied to the determination of the enantiomeric purity (> 99.5% e.e.) of several commercially available samples of camphor.The year has seen several reports of novel procedures for the hydroboration of alkenes. Evans et al. report the use of achiral lanthanoid complexes as catalysts fur the hydroboration of olefins with catech~lborane.~~' The Lewis acidity of the boron atom is thought to be dramatically increased by coordination of the lanthanide (s.9.samarium) to a catechol oxygen atom. The chiral rhodium complex (97) is also an excellent catalyst for the hydroboration of substituted styrenes t(98) -(99)] (Scheme 220 K. Fuji K. Tanaka and H. Miyamoto Tetrahedron Asymmetry 1993,4,247. "' T.Yasukata and K. Koga Tetrahedron:Asymmetry 1993,4,35. '" S.G.Davies N. M. Garrida 0.Ichihara and I. A. S. Walters J. Chem. Soc. Chem.Cornmun. 1993,1153. M.E.Bunnage S. G.Davies and C.J. Goodwin J. Chem. SOC.,Perkin Trans. 1 1993,1375. 224 S.G. Davies 0.Ichihara and 1.A. S. Watters S ?"LETT 1993,461. 225 R.Hulst R. W. f.Zijlstra B.L. Feringa,N.K.de Vries,W. ten Hoeve and H. Wynhrg Tetrahedron Lett. 1993,34 1339. 226 V. Rautenstrauch M. Lindstrom B. Bourdin J. Currie and E. Oiiveros Helv. Chim. Acto 1993,76,607. 227 D.A. Evans A. R. Muci and R. Stiirmer J. Org. Chem. 1993,58,5307. 2'3 N.J. Lawrence 28a).228A process that is equivalent to the hydroboration of alkenes involves selenoalkoxylation and subsequent removal of the seleno group. Deziel et ~1.'~'have introduced a chiral version of this procedure. The C symmetric phenyIseleny1 triflate (100) reacts with alkenes in the presence of an akohol to give anti seIenyl ethers (lUI) which can be reduced to give chiral protected alcohols (Scheme 28b). Alkenes are hydrated in an anti-Markovnikov fashion by titanium(1n) borohydride species or zinc b~rohydride;~~' the lack of both stereospecificity and need of oxidant seems to rule out a hydroboration rnechani~rn.~~ * The hydroboration-oxidation of enamines by Ipc,BH yields fi-amino alcohols with high enantioselectivity (e.e.50_86%).232 Microwave-mediated synthesis has received much attention this year (see also section 5). Amides are prepared simply by heating (5 min) an equimolar mixture of a secondary amine and carboxyiic acid in a microwave Conventional heating (160-180 "C) of a similar mixture requires somewhat longer reaction times.234 Similarly esters are formed from carboxylic acids alcohols and an acid catalyst under microwave irradiati~n.~~' Anhydrides are synthesized from carboxylic acids iso-propenyi acetate and an acid catalyst.236 fi-Aminoesters and /?-lactarns are aIso prepared by rnontmorillonite-catalysed coupling of silyl ketene acetals and imines by the action of microwave radiation.237 '" J.M. Brown D. I. Hulmes and T.P. Layzell J. Chem. SOC.,Chem. Commun. 1993,1673. 229 R. Deziel S.Goulet L. Grenier J. Bordekau and J. Bernier J. Urg. Chem. 1993 58 3619. 230 B.C. Ranu R. Chakraborty and M. Saha Tetrahedron LRft. 1993 34,4659. 23' K.S.Ravi Kurnar S. Baskaran and S. Chandrasekaran Tetrohedrun Lett. 1993,34,171. 232 G. 3. Fisher C.T. Goralski L. W. Nicholson and 3.Singaram Tetrahedron Lett. 1993,34 7693. 233 M. P.Vazquez-Tato SYNLETT 1993,506. 231 8.S. Jursic and 2. Zdravkovski Synth Commun. 1993,23,2761. 235 A. Loupy A. Petit M.Ramdani C.Yvanaeff M. Majdoub B. Labiad and D. Villernin Can. J. Chem. 1993,71 90. 236 D. Villemin B. Labiad and A. Loupy Synth. Commun. 1993,23,419. 237 F. Texier-Boullet R. Latouche and J. Hamelin Tetrahedron tett. 1993 34 2123. Synthetic Methods 295 Some interesting functional group transformations described this year include the conversion of aldehydes into nitriles by the one-pot reaction of the corresponding N,N-dimethyIhydrazone with magnesium rnonupero~yphthalate.~~~ Triphosgene in combination with triphenylphosphine provides a mild reagent for the conversion of primary and secondary alcohols into alkyl chlorides.239 Miller et al. report a convenient conversion of carboxylic acids into alk-1-enes of one less carbon atom by a paIladiurn-catalysed decarbonylatiowdehydration of the mixed-acid-acetic-acid an- h~dride.~~’ Hexamethylene tetraamine txibromide provides a new mild reagent for electrophilic bromination of aromatic compounds.241 The synthesis of chiral organofluorine is currently receiving con- siderable attention.Davis’ group has used the N-F camphorsultam (102)as a chiral electrophilic fluorinating agent to synthesize a-fluoroketones from sodium enolates C(103) + (104)3 (Scheme 29).243The new electrophilic fluorinating agent (105) has seen several uses this year including the fluoro-destannylation of vin~lstannanes,’~~ and the fluorination of alkenes arenes and car bani on^.^^^ The chiral quaternary ammonium fluoride (106)derived from quinine has been used to catalyse the aldol reaction of silyl enol ethers and aldehydes with high enantio~electivity.~~~ N,N,N-trimethyl-1 -adamantylamrnoniurn and proton-sponge fluoride248 provide completely anhydrous sources of fluoride ion.Scheme 29 2’8 R. Fernindez C. Gasch J.-M. Lassaletta J.-M. Llera and J. Vizquez. Tetrahedron Letf. 1993,34 141. 239 I. A. Rivero R.Somanathan and L. H. HelIberg Synth. Commun. 1993.23 71 1. 240 J. A. Miller J. A. Nelson and M.P. Byrne J. Org. Chem. 1993,58 18. 241 S.C. Bisarya and R. Rao Synth. Curnrnun. 1993,23,779. 242 G.Resnati Tetrahedron 1993 49 9385. 243 F.A. Davis P. Zhou and C.K. Murphy Tetrahedron tetr. 1993,34 3971. 244 D. P.Matthews S. C.Miller E.T. Jarvi J. S.Sabol,and J. R. McCarthy Terrahedron Lett. 1993,34,3057. 245 G.S.Lal J. Org.Chem. 1993 58 2791. 246 A. Ando T. Miura T.Tatematsu and T. Shioiri Tetrahedron Left.,1993,34 1507. 247 K.M.Harmon B.A. Southworth K. E. Wilson and P. K. Keefer 1.Ory. Chem. 1993,58 7294. 248 R.D. Chambers E. F. Holmes S. R. Korn and G. Sandford J. Chem. SOC.,Chem. Commun. 1993,855. N. J. Lawrence Amide bases continue to be the topic of many important papers. Collum and coworkers have found that the extremely hindered base lithium bis(2-adaman- ty1)amide (107)is an excellent reagent for the generation of E enolates from ketones (E:2 50 l)(c$ LDA E 2 B 2.5 l).249 Williard has published the X-ray structure of an LDA-THF complex.* The crystalline aggregate prepared from LDA (from diisopropylarnine Iithium metal and styrene in ether) and THF is a bis-solvated dimer.Such studies are undoubtedIy of help to those researchers designing homochiral lithium amide bases. Indeed the X-ray structure of the chiral Iithiurn amide (108) has recently been reported.25' Koga and coworkers have found that the chiral lithium amides (109) and (1lo) the latter containing a fluorinated atkyl group induce high enantioselectivity in kinetic deprotonation of 4-substituted cyclohexanones (Scheme 30).2s2They have also shown that in certain cases the amide bases can further control the alkylation of chiral en01ates.~~' Bunn and Sirnpkins report that the enantiosefectiv- ity of chiral-amide-base-mediateddeprotonation under external quench conditions is improved by the addition of lithium chloride; this now allows direct reaction of the chiral enolate with electrophiles other than silyl chlorides in high enantioselectiv- ity.254Milne and Murphy have used the dilithium salt of norephedrine to effect enantioselective deprotonation of prochiral epoxides thereby providing allylic akohols.' Li I 93% 78 % 8.8.wlh (109) (109) R=€t 74 % 87 % 8.8.with (110) (93% e.e.at -100 "C) (110) R = CHzCF Scheme 30 249 K.Sakuma J. H.Gilchrist F. E. Romesberg,C. E. Cajthami and D. B. Collum Tetrahedron Lert. 1993 34,5213. P.G.Williard and J. M.Salvino J. Org. Chem. 1993 58 1. "' A.J. Edwards S. Hockey F. S. Mair P.R. Raithby R. Snaith,and N. S.Simpkins,J. Org. Chem. 1993,58 6942. 252 K.Aoki H Noguchi K. Tomioka,and K. Koga Tetrahedron Lett. 1993,34 5105. 253 Y. Hasegawa H.Kawasaki and K. Koga Tetrahedron Lett. 1993,34,1963. *" B.J.Bunn and N.S. Simpkins J. Urg. Chem. 1993,58 533. 255 D.Miine and P. J. Murphy J. Chern. SOC.,Chem. Commun. 1993 884. Synthetic Methods Beak and DuZs6report the stereoselective alkylation and silylation [(lll) -+ (1 12)] of carbanions in the presence of (-)-sparteine (Scheme 31). This method for asymmetric carbonxarbon bond formation is unlike that involving chiral lithium amide bases since the chiral catalyst is introduced onIy after deprotonation has occurred. The selectivity is probably a result of interconversion of the dia- stereoisomeric substrate-sparteine complexes since the organoli thiurn is configur-ationally unstable. Scheme 31 Several reports have appeared describing efficient procedures for the resolution of the often-used auxiliary 1,l'-binaphthalene-Z,2'-diol via its N-[(S)-cc-methyben- zylarnine]thiopho~phoramidate~~~ and 0-(-)-menthy1 phosphate.258 Finally Fritz-Langhals2'' reports a useful way to separate diastereoisomers.Conventionally this is carried out by fractional recrystallization or chromatography but in this study the racemic acid (113) is resolved by fractional distillation of the chiraI amides (114)and (1151 using a spinning-band column (Scheme 32). The boiling points of the amides (114) and (115) differ by 7K which allows for efficient separation of optically pure rnateria1. It is highly Iikely that this technique will find many applications. %heme 32 256 P. Beak and H.Du,J. Am. Chem. SOC., 1993,Ii5 2515.257 D. Fabbri G. Delogu and 0.De Lucchi J. Org. Chern. 1993 58 1748. J.-M. Brunel and G. Buono 3. Org. CheM. 1993,58 7313. 259 E. Fritz-Langhals Angew. Chem. Int. Ed. Engl. 1993 32,753.