Reduction with L-selectride

E) configuration. The dipolar cycloaddition of 141 with a silyl nitronate shows a slight increase of facial selectivity over 132 (Eq. 2.9). Because the cycloadducts are converted directly to the corresponding isoxazolines, only the facial selectivity can be determined. It is believed that the cycloaddition proceeds on the Re face of the dipolarophile due to shielding of the Si face by the auxihary. Both chiral auxiliaries can be liberated from the cycloadduct upon reduction with L-Selectride. 

The phenyl 1-thioparatoside 145 was activated with TV-iodosuccinimide and silver triflate and reacted with a convenient derivative of the disaccharide (1-d-GalpNAc-(l ->4)-p-D-GlcpNAc. After removal of the pivaloyl-protecting group with sodium methoxide, isomerization of paratose to tyvelose was performed in a one-pot reaction by oxidation with dimethyl sulfoxide and acetic anhydride, followed by reduction with L-Selectride. Selectivity of the reduction was better... 

Fig. 13.20. Generation of enolates from a,/3-unsaturated ketones via Birch reduction (top line) or by reduction with L-Selectride (bottom line).

In order to achieve chemodifferentiation of the two ketone groups, carbonyl reduction may be carried out prior to NBS-mediated hydrolysis. Reduction with L-Selectride was found to be highly efficient and stereoselective, producing only one diastereoisomer of the product alcohol (Scheme 12). 

Epoxidation of oxonine 93 with dimethyldioxirane, followed by reduction with diisobutylaluminium hydride (DIBAL-H), resulted in a separable mixture of alcohols 95 and 96, and the side product 94 (Scheme 16). Each of the isomers was submitted to Swern oxidation and sequential stereoselective reduction with L-selectride to achieve desired stereochemistry of the products 97 and 98. Formation of the side product 94 was explained by Lewis acidity of DIBAL-H and confirmed by treatment of oxirane derived from 93 with another Lewis acid, AlMe3, to produce oxocine aldehyde 99 in 35% isolated yield <1997CL665>. Similar oxidative synthetic sequence was utilized for the synthesis of functionalized oxonines as precursors of (-l-)-obtusenyne <1999JOG2616>. 

Of the large number of reducing agents, the most useful are DIBAH and lithium tri-i -butylborohydride. Regardless of the nature of R, DIBAH reduces 3 mainly to the alcohol 4 (the tzn/i-Cram product) in 60-80% de. Reduction with L-Selectride usually proceeds in the opposite sense and in aeeordanee with Cram s chelate rule, but high selectivity is observed only when R is a primary or tertiary alkyl group. 

The unsaturated linkage in enantiomerically pure a-methyl-. -y-unsaturated ketones (45) exerted a powerful stereochemical influence on their reduction with L-selectride, particularly when R is a tri-methylsilyl group. The anti homoallylic alcohols (46) were produced with uniformly excellent stereoselectivity (>93 7) via a Felkin transition state in which the double bond occupied the perpendicular position (equation 12). This Felkin selectivity was sufficient to overcome any chelation-mediated contribution in the reduction of a-vinyl-p-hydroxy ketones (47) to the, 2-syn diols (48) with LiEtsBH in THF at -78 °C (equation 13).58... 

Carretero and co-workers found that dqjrotection and cyclization of the vinyl-sulfone 294 produced a 4 1 mixture of 2,3-cu-disubstituted pyrrolidine 295 and its tram isomer (Scheme 40). A/-Alkylation of the nuxture. with 3-chloro-2-chloro-methylprop-l-ene followed by chromatogttqjhy led to isolation of the pure 2,3-c/s product 296, silylation and base-initiated cyclization of which gave indolizidine 297. Ozonolysis and elimination of the sulfone group yieldied another pivotal intermediate, the bicyclic enone 298. Reduction with L-Selectride afforded an inseparable nuxture of two diastereomeric alcohols 299 (9 1). Separation was accomplished only after dihydroxylation with osmium tetroxide and peracetylation of the resdting tetrols. The synthesis of ( )-241 was completed by hyc lysis of the m or tetraacetate 300. 

A similar synthetic route led to 73b starting from (7 )-methyl ester isopropylideneglycerate (77b). However, in this case non-chelation-con-trolled reduction with L-Selectride resulted in poor diastereoselectivity (<60 40). Replacement of the MMT protecting group by the less hindered ethoxy-ethyl (EE) restored high diastereoselectivity (90 10). 

The authors did not proceed to the reduction, obtaining only the Mannich product. Stereoselective reduction with L-selectride. 

The 4-ulose (21) underwent an,ticipated stereoselective reduction with L-selectride to yield the axial alcohol (methyl a-virenoside). The branched-chain aldonic acid (22), related to orthosomycin... 

The configuration of enolates formed by the reduction has been correlated with the preferred ground-state conformation of the a,P-unsaturated carbonyl compound (Scheme 2.35). Thus, Chamberlin and Reich [129] noticed that, upon reduction with L-selectride, enone 113 adopting the s-trans conformation leads to the formation of enolate 114 in a highly stereoselective manner. On the other hand, the Birch reduction of ketone 115, which is kept by the... 

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