Highly Diastereoselective Arylation of (S)-Mandelic Acid Enolate:  Enantioselective Synthesis of Substituted (R)-3-Hydroxy-3-phenyloxindoles and (R)-Benzylic Acids and Synthesis of Nitrobenzophenones

Abstract

An easy access to substituted (R)-3-hydroxy-3-phenyloxindoles, (R)-benzylic acids, and benzophenones is described. The reaction of the lithium enolate of the (2S,5S)-cis-1,3-dioxolan-4-one derived from optically active (S)-mandelic acid and pivalaldehyde with several o- and p-halonitrobenzenes proceeds readily to give the corresponding arylation products in good yields and diastereoselectivities. The reduction of the nitro group with Zn/HCl/EtOH in the o-nitro arylation products with concomitant intramolecular aminolysis of the dioxolanone moiety leads directly to enantiomerically pure (R)-3-hydroxy-3-phenyloxindoles. On the other hand the basic hydrolysis of the dioxolanone moiety in all the arylation products (ortho and para) leads to enantiomerically pure substituted (R)-benzylic acids. The oxidative decarboxylation of these latter with oxygen as terminal oxidant in the presence of pivalaldehyde and the Co(III)-Me2opba complex as catalyst gives substituted nitrobenzophenones.

Enantioselective Synthesis of (S)-3-Hydroxy-3-phenyl-3,4-dihydroquinolin-2(1H)-one Ring System

“…The absolute configuration of the newly formed quaternary carbon atom was then assigned to be S, upon the consideration that the absolute configu-ration of the dioxolanone C-2 carbon atom bearing the tert-butyl group in 2 is S and remains unaltered from 2 to 4. These results indicate that compounds 4 are obtained from the exclusive approach of the o-nitrobenzyl bromides anti to the tert-butyl group, in good agreement with the results reported by Seebach 4,8 and us [1][2][3] in related reactions.…”

In Situ Electrophilic Activation of Hydrogen Peroxide for Catalytic Asymmetric α-Hydroxylation of 3-Substituted Oxindoles

“…The absolute configuration of the hydroxylation products 3a and 3l were established to be R by comparing their optical rotations with that of known enantiomers after removing the N-Boc group. 4,5 The absolute configuration of 3b-3k and 3m-3r were assumed by analogy.…”

Synthesis of oxindoles via reductive CO2 fixation

“…2 In this study, the synthesis of 3-aryl-3-hydroxy-2-oxindoles 1 is focused on, as the skeleton is included in several pharmaceutical compounds such as SM-130686 3 and ECi8. 7 In this context, our retrosynthesis was designed based on reductive CO 2 fixation with (2-aminophenyl)(aryl)methanone derivatives 2, followed by lactam formation (Scheme 1b). Most commonly, oxindoles 1 are synthesized via 1,2addition of an aryl anion equivalent to an isatin derivative.…”