Asymmetric Induction by a Remote Chiral Substituent – Computationally Determined Stereodifferentiation in Michael Additions of α‐Lithiated Allyl Sulfones

Abstract

The mechanism of stereoselectivity has been elucidated for the formation of two stereogenic centers in the products of Michael addition to ethyl crotonate by lithiated α-anions of allylic sulfones bearing a remote chiral N-substituent. In order to single out reactive carbanion structures, their conformational analysis was performed by ab initio calculations, finally at the B3LYP/6-31+G(d) level. Low-energy reactant structures were aligned taking intermolecular steric contacts into account. It appeared that only two cyclic conformers of the sulfone nucleophile in which the Li cation is chelated by the anionic carbon, as well as the S=O and NH moieties, are

Cation−π Interactions in Organic Synthesis

“…Computational analysis of the Li complex 556 shows two conformers A and B (Scheme b). Conformer A with a 3.23 Å distance of aryl···Li + bond is much more stable than conformer B . This resulted in a decrease in the chemical reactivity of conformer 556a - A , and therefore, the preferential stereochemical selection seems to arise from the reaction with conformer 556a - B .…”

The role of an aromatic group in remote chiral induction during conjugate addition of α-sulfonylallylic carbanions to ethyl crotonate

“…Though the precise geometry of the aromatic ring during chelation with the lithiated species is as yet unknown, it evidently plays an important role in determining the approach of the carbanion to the conjugate acceptor and thus the stereoselectivity of the conjugate addition. Preliminary ab initio calculations [ 17 ] for the energetics of approach of 1 to 2 (in the case Ar = Ph) are consistent with these results: the calculations indicate that a remote aromatic substituent in lithiated 1 , in its lowest energy conformation, can come into close proximity (ca. 3.2 Å) with the lithium cation ( Fig.…”

The Synthesis and Base-Induced Breakdown of Triaryl 1,4-Oxathiins—An Experimental and DFT Study

“…Past modelling studies of α-sulfonyl anion chemistry typically account for the metal counterion [48][49][50][51][52][53], although there are exceptions [45,54,55]. This assessment engages a lithium counterion with the α-sulfonyl anion, as part of the transition state for addition to the aldehyde and for the chemistry thereafter.…”