Copper-Catalyzed Hydroalkylation of Terminal Alkynes

Abstract

We have developed a copper-catalyzed hydroalkylation of terminal alkynes using alkyl triflates as coupling partners and (Me(2)HSi)(2)O as a hydride donor. The hydroalkylation proceeds with excellent anti-Markovnikov regioselectivity and provides exclusively (E)-alkenes. We have demonstrated that both alkyl- and aryl-substituted alkynes can be used as substrates, together with 1° alkyl and benzylic triflates. Finally, the transformation can be accomplished in the presence of a wide range of functional groups. Overall, the new hydroalkylation reaction allows highly efficient and diastereospecific synthesis of (E)-alkenes from readily available terminal alkynes and alkyl triflates. On the basis of a preliminary mechanistic study, we propose that the hydroalkylation reaction involves copper hydride formation, hydrocupration of an alkyne, and alkylation of an alkenyl copper intermediate.

Regiodivergent and Diastereoselective CuH‐Catalyzed Allylation of Imines with Terminal Allenes

“…[8,9] When these species are generated in a chemoselective manner in the presence of a suitable electrophile, functional group-tolerant, stereoselective C–C [8] or C–heteroatom [9] bond formation can be achieved. In particular, we have recently described copper-catalyzed reductive addition reactions of olefin-derived nucleophiles to carbonyl and imine electrophiles.…”

“…In particular, we have recently described copper-catalyzed reductive addition reactions of olefin-derived nucleophiles to carbonyl and imine electrophiles. [8a,b,f] Using other metals, several elegant methods for the generation of allylmetal nucleophiles from boro-, [7a,b] carbo-, [7f,g,h] or hydrometalation [7c,d,e] of allenes or 1,3-dienes have been the subject of recent publications. We envisioned that a new hydrocupration–nucleophilic attack strategy to effect stereo- and regiocontrolled allylation of imines would represent a valuable addition to the existing collection of CuH-catalyzed C–C bond-forming transformations.…”

“…We reasoned that subsequent addition of the allylcopper intermediate into imines, followed by ligand exchange with an alcohol [8a,8e,11] could afford either regioisomer of the homoallylic amine and a copper alkoxide species. Subsequent σ-bond metathesis with a hydrosilane would then regenerate the copper hydride and close the catalytic cycle.…”

Ligand‐Controlled Regiodivergent and Enantioselective Copper‐Catalyzed Hydroallylation of Alkynes

“…[6] Shortly after this,Y un and co-workers disclosed ac opper-catalyzed enantioselective hydroallylation reaction of alkenyl boronates with terminal allylic phosphates,t hus providing versatile and highly enantioenriched alkylboron compounds. [8] In contrast, CuH-catalyzed non-asymmetric hydrofunctionalization of alkynes,s uch as semireduction, [9] hydrocarboxylation, [10] hydrobromination, [11] hydroamination, [12] hydroboration, [13] and hydroalkylation [14] have also been disclosed in the last few years.Nevertheless,toour knowledge,the asymmetric version of the hydrofunctionalization of alkynes is hitherto unexploited. [8] In contrast, CuH-catalyzed non-asymmetric hydrofunctionalization of alkynes,s uch as semireduction, [9] hydrocarboxylation, [10] hydrobromination, [11] hydroamination, [12] hydroboration, [13] and hydroalkylation [14] have also been disclosed in the last few years.Nevertheless,toour knowledge,the asymmetric version of the hydrofunctionalization of alkynes is hitherto unexploited.…”

“…[15] 1,4-Dienes (skipped dienes) are synthetically versatile functional groups and ubiquitous structural motifs present in aw ide variety of natural products of biological significance and pharmaceutical drugs. Inspired by the recent reports on CuH catalysis, [5][6][7][8][9][10][11][12][13][14] we envisioned that the enantioselective hydroallylation of alkynes might provide an ideal and straightforward method for the preparation of such optically active units. While these methods mainly focused on either the racemic transformations or the use of stereochemically welldefined precursors,t he catalytic asymmetric version remains largely undeveloped.…”