Reversal of Selectivity in Gold-Catalyzed Cyclizations of 3,3-Disubstituted 1,4-Diynes

Abstract

A general synthetic access to 3,3-disubstituted 1,4-diynes bearing a quaternary carbon center from acetylacetone was developed. The compounds were cyclized to the corresponding enol ethers by cationic gold complexes. The reactions occur in complete exo-selectivity in contrast to compounds incorporating an alkoxy substituent in the 3-position. A mechanistic rationale for this reversal of selectivity is provided.

Synergy between Palladium and Potassium Species for Efficient Activation of Carbon Monoxide in the Synthesis of Dimethyl Carbonate

“…The preparation of 5a was achieved by benzylation of 7 with 1a . When the reaction was performed under the conditions reported by Czekelius et al., 5a was obtained in 86% 17a. The yield of 5a amounted to 89 % when the protocol of Gooden et al.…”

Cycloisomerization of π‐Coupled Heteroatom Nucleophiles by Gold Catalysis: En Route to Regiochemically Defined Heterocycles

“…Similar reaction, by utilizing sterically overcrowded monodentate gold‐carbene complex also revealed endo ‐regiochemistry albeit with low enantioselectivity [327] . The same group observed a reversal of regioselectivity from endo to exo in the cyclization of 3,3‐disubstituted‐1,4‐diynes 229 leading to structures bearing all carbon quaternary centers 230 (Scheme 47, eq 2) [328] . Enantioselective desymmetrization of 1,4‐diynamides 231 leading to enantiopure pyrrolidines 232 are also accessible through this methodology by employing gold(I)‐binol phosphate complex (Scheme 47, eq 3) [329] .…”

Total Synthesis of Mesembrine – The Construction of Quaternary Stereocenters by Gold‐Catalyzed Diyne Desymmetrization

“…Control experiments showed that the different inductive effects of alkoxy substituents do not sufficiently explain this reversal in regioselectivity, since the oxygen atom needs to be incorporated in the substituent carrying the nucleophile in order to steer the reaction towards endo ‐cyclization . In order to account for these observations, a stereoelectronic effect has been proposed (Scheme ).…”