Highly Stereoselective Aldol Condensation Using an Enantioselective Chiral Enolate

Abstract

5a -c) C6H5 ( 2 a -c ) ((1): R = R, f h j : R = R, (0: R = R A tion at the phosphorus atom, and in the case of (2c) for incorporation of the k C triple bond by thermal elimination of trimethylchloro~ilane~~]. Procedure Chlorophenyl(trimethylsily1)methane (72.4 g, 360 mmol) is converted with Mg (10.0 g, 400 mmol) in diethyl ether (200 ml) into the Grignard compound, which is then added dropwise slowly to an ice-cooled solution of PC13 (49 g, 360 mmol) in ether (150 ml). MgClz is removed by filtration and the filtrate is evaporated down under vacuum. Fractional distillation of the residue furnishes 52.7 g (55%) of (lc), b.p.A solution of (lc) (15.0 g, 57 mmol) in ether (200 ml) is treated with 25.3 g (220 mmol) of 1,4-diazabicycl0[2.2.2]0~tane and the mixture is stirred for 12 h at room temperature.The insoluble material is filtered off and washed with ether. The combined filtrates are then evaporated down under vacuum and the amine hydrochloride which precipitates is removed by filtration. After removal of solvent the residue is treated with n-pentane, filtered and the filtrate evaporated down and distilled yield 7.1 g (54%) of (2c), b.p. 51 "C/10-) torr.53"C/10-3 torr ["P('H)-NMR (C6D6): 6=189].

2.06 Formation of Enolates

“…[172][173][174] An authentic copper enolate can be prepared by an alternative route, which involves the conjugate addition of BuCu(BF 3 ). 175 Experimental results indicate clearly that the intermediate is a copper-bonded enolate (12) rather than an α-cupriocarbonyl derivative (13).…”

Asymmetric Induction in Aldol Additions

“…This aldol adduct corresponds to the C13-C23 fragment of tedanolide (28). In 2004, Kuwajima and coworkers performed the total synthesis of the antitumor agent (−)-kazusamycin A (32), and one of the key steps was an aldol reaction between the tin enolate of ethyl ketone 29 with aldehyde 30, which provided the aldol adduct 31 with high diastereoselectivity (de = 93%) (Scheme 5.7). This aldol adduct corresponds to the C15-C24 fragment of the natural product.…”

“…Masamune et al [32] and Heathcock et al [33] made extremely important contributions to the initial studies of aldol reactions involving chiral α-hydroxy ketones. Heathcock brilliantly exemplified the use of ketones 66 and 67, as depicted in Scheme 5.13.…”

Diltiazem Synthesis, Microbial Asymmetric Reduction

“…of 9 was determined for each diastereomer of anti-9 and syn-9. The terms syn and anti were defined according to Masamune et al (18). The microorganisms that produced alcohol 9 with the 3R configuration, which can be used for the synthesis of the enantiomer of diltiazem with high enantioselectivity, are in the genera Absidia, Cryptococcus, and Mucor.…”