Mechanistic Understanding of the Divergent Cyclizations of o‐Alkynylbenzaldehyde Acetals and Thioacetals Catalyzed by Metal Halides

Abstract

The mechanisms of regiodivergent cyclizations of o-alkynylbenzaldehyde acetals and thioacetals catalyzed by Pd and Pt halides are studied. DFT calculations found that both reactions are initiated by electrophilic activation of the acetylenic moiety instead of the previously proposed metal-triggered CX (X=O, S) cleavage. Both the regioselective cyclization of the π-alkyne complex and the chemoselective [1,2]-migration in the carbenoid intermediate were determined as key steps to achieving the observed divergence. For acetal derivatives containing an internal alkyne, the 6-endo-dig cyclization is more favorable and leads to the carbenoid intermediate easily through further steps of CX fragmentation and carbocation cyclization. Then, from the carbenoid intermediate, the [1,2]-migration of sulfur is easier than that of H, Me, and Ph; whereas, a reversed aptitude was predicted for the oxygen analogue, which is consistent with the greater ability of sulfur atoms to stabilize β-carbocations. However, for precursors containing a terminal alkyne, the 5-exo-dig pathway is preferred and only the 1,2-disubstituted indene product is seen, irrespective of the nature of the acetal; thus, a different product from that reported in the literature is predicted for benzaldehyde acetal with a terminal alkyne at the ortho position. This prediction led us to reconsider some of the reported results and hidden realities were uncovered with solid new experimental evidence.

Chiral Cyclometalated Oxazoline Gold(III) Complex-Catalyzed Asymmetric Carboalkoxylation of Alkynes

“…The mechanism of carboalkoxylation reaction of alkynes was previously studied and supported by density functional theory calculation . The cyclization by nucleophilic addition of intermediate IN2 to afford 2aP is believed to be the enantiodetermining step of this reaction (Scheme c).…”

“…The cyclization of IN2 by nucleophilic addition allows the approach of the oxonium [−CH­(OMe) + ] from two directions, i.e., through two different transition states, TS A and TS B , which finally lead to enantiomers of products, ( S )- 2a and ( R )- 2a , respectively. According to the previous mechanistic study, in the structure of transition states ( TS A and TS B ), the gold­(III) center (−[Au]) and the oxonium [−CH­(OMe) + ] have a cis relationship on the pseudo-five-membered ring (Scheme c). Considering the rotation around the Au–vinyl bond, we propose a steric arrangement in which the benzene ring of the substrate is away from the bulky substituent on the chiral oxazoline to minimize the steric hindrance (Scheme d).…”