Synthesis of enantiomerically pure (S)-3-trichloromethylbutyric acid via asymmetric conjugate addition of trichloromethyl metal compounds to a chiral enoate. Activation effect of a sulfonylamino group

Asymmetric conjugate addition

“…MeCu*BF3 reacts with significantly poorer diastereoselectivity. Subsequently, Oppolzer et al demonstrated that other chiral enoates, in which the substrate is made using camphor-derived alcohols, 6 and 7, could be used as well in this reaction with varying degrees of diastereoselectivity (entries [15][16][17][18][19][20][21][22][23][24].1314 Improved results were obtained by adding P(n-Bu)3 to stabilize the organocopper reagent. These chiral auxiliaries and the improved method were used in the synthesis of (S)-citronellic acid (27) from 25 and 26 31 (Scheme l)13 and California red scale pheromone 29 from 28 (Scheme 2).15 More than one chiral center can be established with this method.…”

Synthesis of the marine natural product barbamide

“…Several methods have been reported for the preparation of 4 and the most direct is conjugate addition of a trichloromethyl anion to the chiral crotonyl derivatives 11 and 12. 15,16 Unfortunately, despite several attempts to repeat these reactions on a synthetically useful scale, in our hands generation of either trichloromethylmagnesium chloride 15 or trichloromethyllithium 16 at low temperature for reaction with 11 and 12 respectively did not give acceptable yields of the required product. A more satisfactory approach proved to be resolution of the racemic acid.…”

“…Following hydrolytic cleavage with lithium hydroxide-hydrogen peroxide the required (S)-4 ([a] D 228.9, c 0.96 in EtOH; lit. 15 228.09, c 2.12 in EtOH) was isolated as well as recovered auxiliary, both in quantitative yield. From the retrosynthetic analysis shown in Scheme 1, the next stage of the synthesis of barbamide required a two carbon homologation of (S)-trichloromethylbutanoic acid 4 to give a bketo acid derivative 3 with a suitable leaving group for reaction with (S)-N-methyldolaphenine 2.…”

Synthesis of camphor-derived chiral auxiliaries and their application in asymmetric Morita-Baylis-Hillman reactions

“…3 In earlier studies, we have explored the application of camphor-derived chiral auxiliaries in the asymmetric α-benzylation of carboxylic esters prepared using the borneol derivative 1, 4 Simmons-Smith asymmetric cyclopropanation of α,β-unsaturated acetals prepared using the chiral diol 2, 5 and preliminary asymmetric Morita-Baylis-Hillman (MBH) reactions involving chiral acrylate esters. 6 The chiral auxiliary used in these preliminary MBH reactions was the N-adamantyl-2-exohydroxybornyl-10-sulfonamide (3), and the promising level of diastereoselectivity observed in one of these reactions prompted us to investigate the preparation of a series of N-substituted analogues as potential chiral auxiliaries for asymmetric MBH reactions. Synthetic access to the series of chiral auxiliaries 7 and 8 and the corresponding acrylate ester derivatives 9 and 10 is outlined in Scheme 1.…”