Asymmetric Semipinacol Rearrangement Enabled by Copper-Catalyzed Propargylic Alkylation

Abstract

The merger of two powerful synthetic strategies, i.e., asymmetric semipinacol-type rearrangement and transition-metal-catalyzed propargylic alkylation, has been achieved, delivering a range of enantioenriched cyclo- and heterocyclopentanones with α-alkynylated quaternary stereocenters. Such types of products are challenging to obtain using other methods, and their synthetic value has been demonstrated in a variety of further transformations. The work represents a distinctive mode inducing asymmetric 1,2-carbon migration and further expands the scope of propargylic substitution.

Two Green Protocols for Halogenative Semipinacol Rearrangement

“…Semipinacol rearrangement is a special type of Wagner–Meerwein rearrangement that involves carbocation 1,2-rearrangement to provide carbonyl compounds with an α-quaternary carbon center (Scheme a). It has been strategically used for natural product synthesis and construction of highly congested and synthetically challenging quaternary carbons .…”

“…Semipinacol rearrangement is a special type of Wagner–Meerwein rearrangement that involves carbocation 1,2-rearrangement to provide carbonyl compounds with an α-quaternary carbon center (Scheme a). It has been strategically used for natural product synthesis and construction of highly congested and synthetically challenging quaternary carbons . For examples, semipinacol rearrangement was designed as a key step in the recent total syntheses of lycojaponicumin A, aspidofractinines, gardmultimine A, brevianamide A, illisimonin A, and kopsinitarine E (Scheme a, the quaternary carbon center from semipinacol rearrangement was highlighted in red).…”

Asymmetric Propargylic C−C Bond Formation Using Metal–Allenylidene Species

“…In 2022, Fang's group [53] first explored the semipinacol rearrangement enabled by Cu(I)‐catalyzed propargylic alkylation (Scheme 36). This protocol allowed the formation of the cyclopentanones and oxa‐ or aza‐cyclopentanones bearing α ‐alkynylation quaternary stereocenters in high yields and along with high enantioselectivities.…”

Asymmetric copper-catalyzed alkynylallylic dimethylamination

“…Transition metal-catalyzed η 3 -substitution reactions have been widely used for the construction of different stereogenic centers. [1][2][3][4][5][6] In particular, since the pioneering work of van Maarseveen 7 and Nishibayashi 8 groups, Cu-catalyzed propargylic substitution has emerged as a reliable strategy to introduce C-N, [9][10][11][12][13][14][15][16] C-O, [17][18][19][20] C-C [21][22][23][24][25][26][27][28][29] and C-S 30,31 bonds vicinal to an alkyne unit stereoselectively. In this case, a propargylic leaving group is required to be preprepared for the following generation of a critical Cu-allenylidene intermediate.…”