Enantioselective Allenation of Terminal Alkynes Catalyzed by Copper Halides of Mixed Oxidation States and Its Application to the Total Synthesis of Scorodonin

Abstract

Naturally occurring conjugated allenynes are of general interest owing to their potent and various biological activities. The 1,5‐H transfer of alka‐1,4‐diyn‐3‐yl amines would be one of the most straightforward yet challenging approaches to such compounds since, in principle, two regioisomers may be formed involving two C−C triple bonds. Herein, a catalytic recipe of copper halides with mixed oxidation states, i.e., CuCl/CuBr2, has been identified to address the issues of the side reaction of conjugate addition and the selectivity of 1,5‐H transfer of alka‐1,4‐diyn‐3‐yl amines in EATA (enantioselective allenation of terminal alkynes) reaction involving 2‐alkynals. This method provided various allenynes with excellent enantioselectivities, and was also applied to the first highly enantioselective total synthesis of natural product scorodonin. Mechanistic studies and DFT calculations elucidated the regioselectivity for the observed 1,5‐H transfer.

Alkyl amines and ethers as traceless hydride donors in [1,5]-hydride transfer cascade reactions

“…Considering that the crucial [1,5]-HT step of propargylic amines can be promoted by diverse metals, including [Cu], 7,9–21 [Zn], 22–33 [Au], 34–36 [Ag], 37 [Cd], 38–40 and [Pd], 41–45 we would like to divide the representative examples, for clarity, into six parts that apply different metal promoters.…”

“…In 2022, Ma and co-workers addressed this regioselective challenge, and disclosed the CuCl/CuBr 2 -catalyzed EATA reaction to construct chiral conjugated allenynes ( R )- 24 from 1e , 2-alkynals 26 , and 1-alkynes 3 (Scheme 11). 20 The CuCl/CuBr 2 -mediated asymmetric A 3 -coupling gave chiral 1,4-diyn-3-yl amines 22 , which then underwent CuBr 2 -catalyzed regiospecific and enantioselective [1,5]-HT/elimination through path a, instead of path b, to afford ( R )- 24 with high enantioselectivities (up to >99% ee). Notably, the regioisomer ( S )- 25 was not observed in the process.…”

Functionalized Chromans from ortho-Quinone Methides and Arylallenes

“…ortho -Quinone methides ( o -QMs; 1 ) and allenes ( 2 , Scheme ) , are two classes of reactive intermediates which have been utilized in organic synthesis for various natural and synthetic compounds. Both ortho - and para -quinone methides ( o - and p -QMs) have found their use in various types of reactions such as formal [4 + n ]-cycloaddition/cyclization reactions, nucleophilic additions, oxa-Michael/1,6-additions, oxa-6π-electrocyclizations, many of which also in asymmetric manner, among others. , Allenes have drawn much attention from organic chemists for their unique physical-organic as well as chemical properties, thus prompting the development of various synthetic methods for their preparation . Moreover, numerous natural products also contain allene as their functional group .…”

Nickel-Catalyzed Asymmetric Propargylation for the Synthesis of Axially Chiral 1,3-Disubstituted Allenes

“…In particular, these cumulated dienes have been recognized as versatile synthetic intermediates in complex chemical syntheses, participating in numerous powerful chemical transformations. , The orthogonal relationship between the neighboring π systems within the allene structure exhibits axial chirality, which has inspired the development of enantioselective synthetic methods . In this context, contemporary efforts have focused on devising asymmetric catalytic reactions, including useful asymmetric catalytic approaches based on the transformation of dienes, conjugated enynes, allenyl acetates, vinyl triflates, and terminal alkynes as well as the isomerization of alkynes . To date, the majority of these reports target the synthesis of tri- or tetrasubstituted allenes …”