Asymmetric C(sp)–H Addition of Terminal Alkynes to Cyclopropenes by a Chiral Gadolinium Catalyst

Abstract

We herein report the diastereo- and enantioselective C­(sp)–H addition of terminal alkynes to cyclopropenes by a chiral half-sandwich gadolinium catalyst. This protocol constitutes the first example of asymmetric hydroalkynylation of cyclopropenes with terminal alkynes and offers a straightforward and 100% atom-efficient route for the synthesis of a wide range of enantioenriched alkynylcyclopropane derivatives in high yields (65–96%) and excellent stereoselectivity (>20:1 dr; 90–99% ee). Elaboration of some of the alkynylcyclopropane products through selective transformation of the CC moiety has also been demonstrated to give further diversified chiral cyclopropane derivatives which are otherwise difficult to access.

Cobalt‐Catalyzed Diastereo‐ and Enantioselective Hydroalkenylation of Cyclopropenes with Alkenylboronic Acids

“…In the field of catalytic enantioselective functionalization of cyclopropenes, Rh‐catalyzed hydrostannation, hydroboration, hydroformylation, hydroacylation, and Cu‐catalyzed hydroboration, hydronitronylation, carbocupration, carbozincation, carbomagnesiation, hydroallylation, and Fe‐ and Pd‐catalyzed carbozincation, and lanthanide‐catalyzed hydroamination, hydroalkynylation, addition of 2‐methyl azaarenes, and NHC‐catalyzed hydroacylation have been disclosed for enantioselective preparation of various functionalized cyclopropanes (Scheme b). However, introduction of diversified alkenyl groups onto a cyclopropyl ring has been rarely reported despite all the strategies mentioned above .…”

A Short Synthesis of (+)‐Brefeldin C through Enantioselective Radical Hydroalkynylation

“…Due to its obvious synthetic interest, the enantioselective hydroalkynylation of unactivated alkenes has been recently reinvestigated but its scope remains so far limited to electron‐rich and ‐poor alkenes . The only unactivated alkenes that were enantioselectively hydroalkynylated were strained system such as cyclopropene and norbornene derivatives and aryl‐substituted conjugated dienes . The simple enantio‐random hydroalkynylation of nonactivated alkenes with Markovnikov regioselectivity has been described in 2017 by Cui and co‐workers using iron catalysis .…”

Synthetic Applications of Cyclopropene and Cyclopropenone: Recent Progress and Developments

“…Increasing aliphatic substituents at the end of the alkyne 47 leads to a decrease in the yield of the reaction. Dian et al [32] in 2020 developed a Pd(OAc) 2 catalyzed enantioselective hydroalkynylation reaction of achiral cyclopropenes 46 by the addition of different terminal alkynes 47 with Pd(acac) 2 and (R)-DM-BINAP as a chiral ligand to provide enantiomerically enriched alkynylated cyclopropanes 49 with excellent diastereo-and enantioselectivity (Scheme 7).…”