Stereoselective acylations

Stereoselective Acylations. Intramolecular Ftiedel-Crafts acylation reaction of A/-ataLkyl a-amino acid detivatives gives cycHc ketones with high enantioselectivity (100). This methodology has been used for the enantiospeciftc syntheses of tylophorine [482-20-2] and cryptopleutine [87302-53-2] the ptincipal representatives of phenanthroiadolizidine and phenanthroquiaolizidine alkaloids (qv) (101). 

Enzymatic desymmetrization of prochiral or meso-alcohols to yield enantiopure building blocks is a powerful tool in the synthesis of natural products. For example, a synthesis ofconagenin, an immunomodulator isolated from a Streptomyces, involved two enzymatic desymmetrizations [149]. The syn-syn triad of the add moiety was prepared via a stereoselective acylation of a meso-diol, whereas the amine fragment was obtained by the PLE-catalyzed hydrolysis of a prochiral malonate (Figure 6.56). 

The stereoselective acylation of a prochiral chromanedimethanol derivative by VA in the presence of CAL-B gave the corresponding (S)-monoester in high enantiomeric... 

To a much smaller extent non-enzymic processes have also been used to catalyse the stereoselective acylation of alcohols. For example, a simple tripeptide has been used, in conjunction with acetic anhydride, to convert rram-2-acctylaminocyclohexanol into the (K),(R)-Qster and recovered (S),(S)-alcohol[17]. In another, related, example a chiral amine, in the presence of molecular sieve and the appropriate acylating agent, has been used as a catalyst in the conversion of cyclohexane-1(S), 2(/ )-diol into 2(S)-benzoyloxy-cyclohexan-1 f / j-ol1 IS]. Such alternative methods have not been extensively explored, though reports by Fu, Miller, Vedejs and co-workers on enantioselective esterifications, for example of 1-phenylethanol and other substrates using /. vo-propyl anhydride and a chiral phosphine catalyst will undoubtedly attract more attention to this area1191. 

Stereoselective acyl migration of amino acid derivatives has been reported (Scheme 32).55... 

A Sharpless asymmetric epoxidation features in a synthesis of (S)-chromanethanol (15). In the key cyclisation step, the absolute configuration of the diol is retained by a double inversion (95SL1255). trans-6-Cyano-2,2-dimethylchroman-3,4-diol is obtained from the racemic diol with excellent optical purity by the stereoselective acylation using Candida cylindraceae lipase (95TA123). 

The use of biosynthetic methods to stereoselectively acylate iV-hydroxymethyl substituents on some bicyclic /3-lactams has been mentioned in Section 2.04.8.1 <2003TA3805>. 

Stereoselective reduction of chiral 2-alkyl-3-keto amides. The chiral propionamide (1) derived from tran.t-2,5-bis(methoxymethoxymethyl)pyrrolidine undergoes stereoselective acylation of the enolate in the presence of ZnCh to give 2-alkyl-3-oxo amides (2). These products undergo reduction with zinc borohydride to give syn-2-alkyl-3-hydroxy amides (3). 

Stereoselective acylation of racemic secondary akohols. I he reagent acylaies a chiral secondary alcohol (2) to give the (S)-ester (3a) and the (R)-ester (3b). The product ratio of (3a) to (3b) was determined by F-NMR. (S)-Diastereoisomers are preferentially formed. 

Oxazolidinone auxiliaries were also employed for stereoselective acylation reactions of imide enolates with acid halides [158]. For example, the lithium enolate of the imide 223 reacted... 

Luetzen, A, Koell, P, D-Xylose derived oxazolidin-2-ones as chiral auxiliaries in stereoselective acylations and halogenations. Tetrahedron Asymmetry, 8, 29-32, 1997. 

In many of the examples reported the amide. V-substitucnts bear protected hydroxy groups, which can be unmasked in order to facilitate hydrolysis at a later stage. The amides of the /ra/7.v-2,5-bis(mcthoxymcthoxymethyl)pyrrolidinyl chiral auxiliary refer to enantiomerically pure substrates. These substrates can be obtained by stereoselective acylation of the corresponding chiral amide enolates (see Section D. 1.3.4.2.3.1.). 

Phenyl trifluoromethylketen, obtained by zinc dechlorination of the appropriate a-chloroacyl chloride, (itself derived from a-trifluoromethylmandelic acid), has found use as a reagent for the stereoselective acylation of chiral secondary... 

Recently a study of the stereoselective acylation of ot-aryl alkylamines 17 by phenyl trifluoromethylphenylketene 16 was done (ref. 10,11). The temperature dependence of the relative amounts of the diastereomeric products 18 and 19 indicated that for pairs of corresponding reactions (ref. 12,13) the zero selectivity temperature (ref. 11) varies considerably with the structural features of the amine 17. 

Shioji K, Tashiro A, Shibata S, Okuma K (2003) Synthesis of bifunctional P-chiral hydroxy phosphinates lipase-catalyzed stereoselective acylation of ethyl (1-hydroxyalkyl) phenylphosphinates. Tetrahedron Lett 44 1103-1105... 

Kamijo S, Hoshikawa T, Inoue M (2010) Regio- and stereoselective acylation of saturated caibocycles via Nortish-Yang photocyclization. Tetrahedron Lett 51(5) 872-874... 

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