Anri-selective

Reduction of a-methyl-fi-hydroxy ketones,2 The r-butyldimethylsilyl ethers of these ketones, in which chelation is difficult, are reduced by lithium aluminum hydride with a high degree of 1,2-anri-selectivity. This reaction can therefore afford either aM ,a/iri-l,3-diols or anti,syn- 1,3-diols with high selectivity. 

The present procedure is a modification of that originally reported by the submitter and co-workers.2 This procedure is applicable to a large scale preparation of the title compound in high overall yield (-80%) without purification of the intermediates by chromatography. The title compound is reported to be a useful reagent for anri-selective aldol reactions with dicyclohexylboron triflate and triethylamine as enolization reagents.3... 

This hydrosilylation is particularly useful for highly anri-selective reduction of a-amino or a-hydroxy ketones with no detectable racemization. 

Stereoselective dihydroxylation. The 0s04-catalyzed dihydroxylation of 5-vinyl-4,5-dihydroisoxazoles (1) (obtained by reaction of the nitrile oxide derived from nitroethane with 1,3-dienes) is ant/-selective, and the anri-selectivity is markedly enhanced by a cw-substituent on the double bond. 

Michael reactions. anri-Selectivity is observed in the reaction of tributyltin enolates with enones. On the other hand, using butyldichlorotin diisopropylamide as enolization agent the major products are the sy/t-isomers. 

In addition to the acetate aldol problem, stereoselective aldol additions of substituted enolates to yield 1,2-anti- or f/treo-selective adducts has remained as a persistent gap in asymmetric aldol methodology. A number of innovative solutions have been documented recently that provide ready access to such products. The different successful approaches to anri-selective propionate aldol adducts stem from the design of novel auxiliaries coupled to the study of metal and base effects on the reaction stereochemistry. The newest class of auxiliaries are derived from A-arylsulfonyl amides prepared from readily available optically active vicinal amino alcohols, such as cw-l-aminoindan-2-ol and norephedrine. 

Additive aldol reaction. An anri-selective synthesis of 5-phenylthio esters of 3-hydroxy-2-phenylthiomethylalkanethiolates from a mixture of acryloyl chloride, PhSLi and aldehydes is mediated by MgBr2 OEt2. 

The anri-selective aldol reaction between cyclohexanone and ArCHO reaches >99% ee if it is conducted in the presence of trawi -4-(4-t-butylphenoxy)-L-piDline and sulfated P-cyclodextrin in water at room temperature. Another catalyst is cw-A-fl-adamantane-carboxamido)-(5)-proline (1) in conjunction with P-cyclodextrin. ... 

Under the same conditions, similar anri-selective aldol reactions obtain with several other chiral ethyl ketones such as 3.4... 

It is interesting to note that anri-selectivity of aldolization (with L-proline promotion) involving hydroxyacetone as the donor is switched in the Mannich reaction. Thus syn-2-hydroxy-3-arnino ketones are obtained as major products. 

AttylationJ These allylating agents react with aromatic aldehydes in a y- and anri-selective maimer. 

Aldol reactions. Titanium -ate complexes effect anri-selective aldolization (5 examples, 72-81%). 

Allylation and alkynylation. Anri-selective allylation of aldehydes with... 

Z)-Alkenylstannanes The hydrostannylation of 1-alkynes in the presence of a Lewis acid is anri-selective. 

Thioallylation. Allylzirconium species derived from allenyl sulfides react with carbonyl compounds in an anri-selective fashion to give 4-hydroxy-3-sulfenyl-l-alkenes. 

Addition of -butylmagnesium bromide to 624 followed by Swem oxidation affords the ketone 642. Zinc borohydride addition occurs with almost exclusive anri-selectivity (>99 1), leading to 646 in accordance with an a-coordinated transition-state model in which the r -face of the carbonyl is exposed to the reagent. Presumably the MOM-ethers display a crown ether effect to facilitate a-chelation. In marked contrast, L-Selectride shows excellent 5y -selectivity to provide 645 (92 8), consistent with a j5-chelation and/or Felkin— Anh model. The a ri-adduct 646 is converted in five steps to ketone 647, which undergoes a similar highly selective hydride reduction with zinc borohydride to yield the anti,syn,syn-alcohol 648 (96 4). This product is converted in six steps to the r n5-(2i ,57 )-pyrroline 649, which undergoes a Wacker oxidation followed by catalytic reduction to (— )-indolizidine 195B (650) and its C-5 epimer (86 14) (Scheme 142). 

Stereoselective reactions with acetals. Noyori et al. (10,438) have used this Lewis acid to promote an aldol-type reaction between enol silyl ethers and acetals and have noted high. syn-selectivity in this process. Molander and Haar report that reaction of acetals with cyanotrimethylsilane promoted by TMSOTf results in a-alkoxy cyanides and that this reaction can be diastereoselective when the acetal is substituted at the 4-position by an alkoxy group. The diastereoselectivity depends on the nature of the acetal and the 4-alkoxy group. Dimethoxy acetals show slight diastereoselectivity, but diisopropoxy and dibenzyl acetals can show diastereoselectivity of 5-10 1. The diastereoselectivity also depends on the type of 4-substituent. Acetoxy and t-butyldimethylsilyloxy groups have no effect on the diastereoselectivity, but methoxy, benzyloxy, and allyloxy groups promote anri-selectivity. Since a metal template is not involved, the diastereoselectivity... 

Scheme 2.20 anri-Selective asymmetric conjugate addition of aldehydes to nitrooleflns... 

From chiral non-carbohydrates. - Several syntheses of amino-sugars from chiral non-carbohydrate starting materials have been reported. The a-L-daunosamine derivative 48 was obtained from L-aspartic acid via the known lactone 47, which was prepared in 2 steps. Key reactions were the anri-selective Grignard addition and syn-selective epoxidation (steps i and ii,... 

The 1,3-anri selectivity is maintained in the presence of an a-substituent, i.e. in substrates such as (8). Thus diisopropylsilyl-ation/hydrosilylation of both diastereomers of (8) gave the 1,3-trons -siladioxane (9), with dr > 250 1 (eq 2). However, with the more challenging substrates (10) the a-position was found to have more influence. Both diastereomers gave principally the 1,2-trans product (11) (eq 3) but, while onft-(lO) resulted in dr = 97 1, sy -(10) gave only dr = 5 1. 

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