Enantioselective Hydroalkynylation of Non‐Polar Carbon‐Carbon Double Bonds: Iridium‐Catalyzed Asymmetric Addition Reaction of Terminal Alkyne CH Bonds to Substituted Norbornadienes

Abstract

This update describes the enantioselective addition of the terminal alkynyl C À Hb ond across an on-polar C=Cd ouble bond. Sterically congested substrates are often challenging in this type of reaction as these alkenyl substrates exhibit poor substrate-metal center coordination, and thus poor stereo-induction would result. Thes uccessfule nantioselective hydroalkynylationo ft his type of system has sporadically been reported.W eh erein describe our progress for the example of vinyl-substituted norbornadiene derivatives.W ith the aid of an iridium complex in combination with the chiral SYN-PHOS ligand, the addition products couldb eo btained smoothlyw ith excellent enantioselectivities (up to 99% ee). In particular, the first examples of an acetylenic C À Hb onda dding across azanorbornadienes are also disclosed.Keywords: alkynes; asymmetric catalysis; C À H bonds;iridium; synthetic methods Hydroalkynylations of polarc arbon-oxygen/nitrogen doubleb onds,f or instance,o fa ldehydes,k etones, imines,e nones and related compounds,h ave been remarkably successfuls ince the late 1980s.[1] In fact, it is not surprising that this addition reactiono ffers exceptionallyh igh regioselectivity across the polarized carbon center.[2] Even thoughe xtensivep rogress in carbonyl-type hydroalkynylations hasb een achieved, the regioselective and enantioselective addition of the terminal alkyne C À Hb ondt oanon-polar or nonfunctionalized C=Cd ouble bond is stillagreat challenge.[3] Recently,chemists have employed specially ligated transitionm etal complexes to promote reactions between terminal alkynesa nd allenes, [4] 1,3-dienes, [5] cyclopropenes, [6] norbornadienes, [7] andvinylarenes.[8] Yet, only non-enantioselectivev ersionso f these reactions were mainly reported. Thed evelopment of asymmetric hydroalkynylations of non-polar C=Cb onds remains limited.In 2008, Hayashi andc o-workers disclosed the first Rh-catalyzed asymmetric hydroalkynylationo fa llenes.[9] Fort he allene moiety it was necessary to have proximal coordinating ability (e.g.,adiphenylphosphinyl group) in ordertoachieve agood enantioselective outcome.L ater the same group (Nishimura and Hayashi)d eveloped ac obalt-Josiphos-type catalyst systemf or handling substrates without such an eighboring coordinating group.[10] In 2010, Suginome showedt he first nickel-catalyzed asymmetric addition of at erminal alkyne C À Hb ond to 1,3-dienes.[11] The trans-configuration of the dienes andu nique a-siloxya,a-sec-alkyl-containingalkyneswere found to be crucial reactionp artners for achieving high enantioselectivity.A part from these specially madea lkene/allene and alkyne substrates,t here are only af ew recent literature reports on the asymmetric alkynylation of non-polar norbornadienes (NBDs). Giordano and Buono reported the use of aP -chiral palladacyclic complexf or promoting hydroalkynylationw ith 24-36% ee.[12] Good-to-excellente nantioselectivities were reported by Fana nd co-workers using an Rh-Josiphos-type complex. [13] Recently,N ishimura and Hayashi d...

Versatile Catalytic Reactions of Norbornadiene Derivatives with Alkynes

“…In 2015, the first enantioselective addition of C−H bonds of terminal alkynes to alkenyl‐substituted norbornadienes ( 22 ) and azanorbornadienes was reported [Eq. (10)] …”

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 .…”

Construction of Acyclic Quaternary Carbon Stereocenters by Catalytic Asymmetric Hydroalkynylation of Unactivated Alkenes

“…First, the catalyst must be capable of overcoming significant steric hindrance for the formation of quaternary carbon stereocenters. Current catalytic systems for hydroalkynylations are limited to disubstituted alkenes including α,β-unsaturated compounds and activated alkenes, leading to the formation of alkyne-substituted tertiary carbon stereocenters . Second, the catalyst must exert substantial regio-control because the hydroalkynylation could occur at the less substituted site of the alkene.…”