Conjugate reduction, asymmetric

General procedure for asymmetric conjugate reduction of a, -unsaturated esters [31]... 

Zhu and Burgess have reported an asymmetric conjugate reduction of 1,3-enol ether esters (Table 9) and 1,3-enol ether alcohols (Table 10) [72]. Initial reaction conditions reached full conversion of E-l-methoxy-l-phenylethene using ligand 9 albeit with a very low enantioselectivity of 29%. 

Recently, List has described a cascade reaction promoted by phosphoric acid 1 in combination with stoichiometric amounts of achiral amine, which transforms various 2,6-diketones to the corresponding ds-cyclohexylamines (Scheme 5.28) [50]. This three-step process involves initial aldolization via enamine catalysis to give conjugate iminium ion intermediate A. Next, asymmetric conjugate reduction followed by a diastereoselective 1,2 hydride addition completes the catalytic cycle. 

A direct asymmetric reductive Mannich-type reaction that allows for the formation of three contiguous stereocentres with high chemo-, diastereo-, and enantio-selectivity (10 1 to 50 1 dr, 96-99% ee ) has been presented (Scheme 4). The reaction commences with the formation of the corresponding iminium ion from aldehyde (122) and prolinol (g) catalyst (125), followed by conjugate reduction with Hantzsch ester (123) to generate an enamine, which then undergoes Mannich reaction with imine (124) to produce (126).179... 

In addition to being an efficient chiral controller in a number of stereoselective transformations of chiral acrylates, (i.e. the Diels-Alder reaction, the conjugate reduction, the asymmetric dihydroxylation, and the nitrile oxide cycloaddition ) the bomanesultam (11) has been shown to be an exceptionally efficient chiral auxiliary for stereoselective aldol condensations (eqs eq 3 and eq 4). Depending upon the reaction conditions, A -propionylsultam can produce either the syn or anti aldol product with an excellent diastereoselectivity, Furthermore, good diastereoselectiv-ities are also observed for the corresponding acetate aldol reaction (eq 5), ... 

The various possibilities for the preparation of chiral allylic amines or a aryl substituted amines are outlined in Figure 1.9. Although the addition reaction of a carbon nucleophile to an imine derived from an aryl substituted aldehyde is very efficient (B), the related addition to an a,p unsaturated imine (A) can sometimes proceed via a 1,4 addition pathway. Similarly, the asymmetric C=N reduction reaction (C and D) is sometimes hampered by the possibility of either obtaining conjugate reduction (in the case of C) or low enantioselectivities (in D when R = aryl). The addition of sp hybridized carbanions to imines (E) is a particularly effective... 

Conjugate reduction. p,p-Disubstituted a,P-unsaturated esters undergo asymmetric reduction by polymethylhydrosiloxane in the presence of r-BuONa and a complex derived from CuCl and a slightly modified (i.e., p-tolyl) (5)-BINAP. 

Keywords Conjugate reduction Enolate C - C bond formation -Asymmetric catalysis Reductive aldol Reductive Mannich... 

Very high ee values have been obtained in the asymmetric conjugate reduction of Q , unsaturated esters and amides with NaBH4 in the presence of a chiral semicorrin (a bidentate nitrogen ligand) cobalt catalyst. Good to excellent ee values were realized in the reduction of oxime ethers with NaBHa-ZrCU in the presence of a chiral 1,2-amino alcohol. ... 

Duan et al have synthesized a series of chiral alkylphosphonates (449) bearing a )5-stereogenic center in good enantioselectivities (up to 95% ee) via the CuH-catalyzed asymmetric, conjugate reduction of jS-substituted a,j8-unsaturated phosphonates (448) under optimal conditions using Cu(0Ac)2 H20 as the copper source, (R)-SEGPHOS as the ligand, polymethylhydrosiloxane as the siloxane, and /-BuOH as the additive (Scheme 111). 

Scheme 2.3 Asymmetric counteranion directed conjugate reduction of enals citral and dtroneUal...

In addition to molecules containing prochiral sites, racemic molecules can participate in catalytic asymmetric transformations. In some transformations, the stereocenter is destroyed in the course of the reaction, and equilibrating prochiral intermediates are formed. An example of such a process is the asymmetric arylation of ketones (Figure 14.8C). In other cases, one of the enantiomers of the substrate reacts with the asymmetric catalyst significantly faster than the other enantiomer. In this case, an enantioenriched product is formed, and the opposite enantiomer of the reactant remains. This last process is called a kinetic resolution and is illustrated for the conjugate reduction of enones via hydrosilylation (Figure 14.8D). In this case, the top and bottom faces of the C-C double bond are diastereotopic because reaction at each face of the enone generates diastereomeric products. This section of the chapter first presents the principles that relate to reactions at prochiral centers of achiral substrates and then presents the principles that relate to reactions of racemic or meso compounds. 

In order to explain this DKR, it was proposed that a copper enolate intermediate was formed on asymmetric conjugate reduction of the enone. Subsequent a-bond metathesis with silane yielded the silyl enol ether and regenerated the copper hydride catalyst. Under basic conditions, a rapid... 

In this section we describe only those systems that lead to the 1,4-conjugate reduction mode. Issues of relative and absolute stereoselectivity are also of considerable importance when sp carbon atoms are converted to potentially asymmetric sp centers. 

An extension of this work was reported by the same research group for the asymmetric conjugate reduction of a,p-unsaturated ketones 65, affording final reduced products 67 with high yields and good to excellent enantioselectivities (Scheme 25) [136]. 

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