Re-orienting coupling of organocuprates with propargyl electrophiles from S_N2′ to S_N2 with stereocontrol

Abstract

Diorganocuprate(I) reagents derived from lithiated heterocycles and CuCN react with enantioenriched secondary propagryl bromides to give the corresponding propargylated heterocycles. While propargyl electrophiles typically undergo SN2′ displacement, this transformation represents the first example of the reaction of hard carbanions with propargyl eletrophiles in an SN2 fashion and occurs with excellent levels of stereoinversion. The new method was applied to the formal synthesis of (+)-frondosin B.

α‐ and γ‐Regiocontrol and Enantiospecificity in the Copper‐Catalyzed Substitution Reaction of Propargylic Phosphates with Grignard Reagents

“…In contrast to the asymmetric synthesis, α‐substitution reactions of enantiomerically enriched propargylic alcohol derivatives have been reported. Substrates/reagent systems published to date are ammonium salt/ArMgBr/Cu cat., [7] salicylate/ArMgCl/Cu cat., [8] ester/cuprate, [9] bromide/heteroaryl cuprate, [10] and sulfonate/TMSCF 3 /Cu cat./KF [11] . In addition, indirect methods to access α‐substituted acetylenes have been published [12] .…”

Suzuki coupling-based synthesis of VATPase inhibitor archazolid natural product derived fragments

“…The requisite vinyl iodide 18 was prepared from alkynol 19, available in by enantioselective Noyori reduction 25 of the corresponding alkynone. 26 Red-Al reduction of the alkyne in 19 to the trans-alkene, TES protection of the alcohol, and iododesilylation of the TMS group gave 18 in 37% yield for the three steps. The Suzuki coupling with boronic ester 10 again proceeded efficiently, in this case using Pd(dppf)Cl 2 and Cs 2 CO 3 as base in DMF at room temperature, 27 giving the coupled product 17 in 80% yield.…”

Copper‐Catalyzed Selective Cross‐Couplings of Propargylic Ethers with Aryl Grignard Reagents

“…Iron catalysts show advantages in cross‐couplings of propargylic electrophiles with Grignard reagents, while the stereoselectivity of the reactions needs to be elucidated (eq 2) . Stereospecific propargylic coupling were recently achieved by using propargylic ammonium salts as an electrophile (eq 3) and diorganocuprate(I) reagents (eq 4) . In general, the electrophiles used in these reactions are prepared from the corresponding propargylic alcohols.…”