Asymmetric reduction, reagent controlled

In this model the sense of asymmetric induction is controlled by two principle factors (i) coordination of borane on the least-hindered face of the bicyclic ring system and (ii) coordination of the Lewis acid syn to the small group (R ). The latter point is in good agreement with the structural data that has been presented in this chapter, and is further supported by results from the asymmetric reduction of oxime ethers (Figure 51). As predicted by the model (75 and 78), (E) and (Z)-oxime ethers afford enantiomeric amines upon reduction by the reagent derived from (-)-norephedrine and borane (2 equiv.). Here, Lewis acid coordination is dictated by the ( )/(Z) stereochemistry of the oxime ether rather than by the rule of coordination syn to the small group. 

The synthesis of 112 was then modified to provide a single enantiomer. This called for an asymmetric synthesis of cyclization substrate 111. This was accomplished by Midland reduction of ketone 113 to provide 114 with excellent enantioselectivity (Steroids-21). Alkylation of 114 with the appropriate bromide (prepared from 2-methylfuran according to the procedures described on Steroids-18), followed by a few well-precedented reactions, gave 115, and thence 111 and 112. Application of the Midland reduction is notable. This is a relatively early application of a reagent-controlled asymmetric synthesis. It is also notable that the Midland method works extremely well on alkyl alkynyl ketones (because they look like aldehydes to the reagent) and thus, is well-suited to this application. ... 

The first noncarbohydrate-based asymmetric synthesis of kedarosamine uses the A,0-protected D-threonine 166. It is first converted into the corresponding Weinreb amide via the acyl chloride. Subsequent coupling with the allyl Grignard reagent provides 167. The nonchelation controlled reduction of ketone 167 with NaBH4 is syn selective, whereas 1,2-chelation controlled reduction... 

In 2005, Huang et al. reported a tandem asymmetric conjugate reduction-fluorina-tion reaction by an efficient combination of iminium and enamine catalysis using two distinct secondary amine catalysts [16]. This method offered direct access to chiral multifunctionalized aldehydes from P-substituted enals and electrophilic florinated reagents in a biomimetic way (Schane 9.13). The diastereoselectivity of the products varied depending on the catalyst combination (Scheme 9.14). The chemistry presented here demonstrated for the first time the power of the multicatalysis process for control of the product diastereoselectivity based on the cycle-specific catalysis concept. 

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