Synthesis of Conjugated Boron‐Enynes via cis‐Alkynylboration of Terminal Alkynes

Abstract

A unique and practical Cu-catalyzed cisalkynylboration of terminal alkynes with diboron reagents and bromoalkynes has been realized. This process enables the convenient synthesis of a large variety of trisubstituted enynylboronates under mild reaction conditions with broad functional-groups compatibility, high regioselectivity and stereoselectivity. The usability and practicability of this process was further demonstrated by the successful modular synthesis of enediynes. Scheme 3. Gram-scale experiment and derivatization of product. Scheme 4. Modular synthesis of enediynes from three simple alkynes. Scheme 5. Plausible catalytic cycle.

First-Row d-Block Element-Catalyzed Carbon–Boron Bond Formation and Related Processes

“…Treatment of these skipped dienes with DBU promotes dehydrohalogenation to generate dendralenes . Alkynyl bromides are also suitable for a copper-catalyzed cis -alkynylborylation to produce trisubstituted boryl-containing conjugated enynes with high regio- and stereoselectivity (Scheme c) . While terminal alkynes undergo a copper-catalyzed 1,1-boroalkylation with diazocompounds and B 2 pin 2 , internal alkynes are efficient substrates in a copper-catalyzed regio- and trans -selective silaboration reaction affording tetrasubstituted alkenes …”

“…639 Alkynyl bromides are also suitable for a copper-catalyzed cis-alkynylborylation to produce trisubstituted boryl-containing conjugated enynes with high regio-and stereoselectivity (Scheme 179c). 640 While terminal alkynes undergo a copper-catalyzed A ligand-free, chemoselective trifunctionalization of 2ynamides generates oxindoles via a borylative arylation of the alkyne (Scheme 180a). Interestingly the putative intermediate, an exocyclic α,β-unsaturated amide, is not observed, suggesting that nucleophilic borylation of this species is faster than the initial carboboration.…”

Copper-Catalyzed Borylative Difunctionalization of π-Systems

“…Unsymmetrical arylalkynes could be used with excellent regiochemical outcomes when substituted with primary alkyl groups ( 141c ); however, less differentiated systems showed lower selectivity ( 141d ). A similar methodology was reported in the following year by Gong and Fu (Scheme , Condition B), utilizing terminal alkynes as the initial π-acceptor to generate the corresponding boryl-functionalized trisubstituted olefin . Intramolecular competition experiments suggested that a terminal alkyne is more reactive to the copper–boryl complex compared with both an internal alkyne and a monosubstituted olefin.…”

“…A similar methodology was reported in the following year by Gong and Fu (Scheme 36, Condition B), utilizing terminal alkynes as the initial π-acceptor to generate the corresponding boryl-functionalized trisubstituted olefin. 102 Intramolecular competition experiments suggested that a terminal alkyne is more reactive to the copper−boryl complex compared with both an internal alkyne and a monosubstituted olefin. In both cases, the proposed termi- nation proceeds through an oxidative addition to the alkynyl bromide followed by reductive elimination.…”

Synthesis of Tri‐ and Tetrasubstituted Alkenyl Boronates from Alkynes

“…Fañanas‐Mastral group prepared dendralenes by syn ‐addition of 1,4‐dibromo‐2‐butenes to alkynes after dehydrobromination (Scheme 29a) [79b] . Later, Yun [80a] and Gong/Fu [80b] have used bromoalkynes to obtain, after syn ‐carboboration, enynylboronates as products (Scheme 29b), using respectively internal or terminal alkynes.…”