Highly Diastereo‐ and Enantioselective Cu‐Catalyzed Borylative Coupling of 1,3‐Dienes and Aldimines

Abstract

AC u-catalyzed diastereo-and enantioselective borylative coupling reaction of 1,3-dienes with imines was realized. Branched homoallylic amines are readily prepared in as yn-selective manner with high regio-, diastereo-and enantioselectivity.M oreover,t hese three-component coupling reactions feature good functional-group compatibility and easy access to the substrates and catalyst.Asymmetric allylation reactions [1] of imines have received increasing interests from the synthesis community [2] because enantioenriched homoallylic amine products are useful building blocks in organic synthesis and medicinal chemistry.[3] Copper catalysis is an efficient approach to promote the enantioselective addition of terminal allyl transmetalation reagents (e.g., with B, Si, and Sn) to imines, [4] however,C ucatalyzed asymmetric, nucleophilic addition to imines with functionalized (e.g., g-substituted) allyl metal reagents remain challenging.T his is probably due to inefficiencyo f the transmetalation event arising from increased steric hindrance,t he weak electrophilicity/reactivity of imines, and/or difficulties in predicting the regio-and stereochemical outcome of additions.N ew and efficient approaches to generating and utilizing functionalized allyl metal reagents in the presence of acopper catalyst hold promise for accessing complex homoallylic amines,a nd these methods will expand the application of catalytic asymmetric allylation chemistry.Since the seminal work of borylcopper catalysis reported by the Ito [5] and the Miyaura [6] groups,C u-catalyzed borylative coupling reactions have been recognized as an important method for generating boron-containing organocopper species in situ from an unsaturated hydrocarbon. [7] In this context, Hoveyda pioneered the use of boron-functional allylcopper intermediates in enantioselective allylation of aldehydes/ketones, [7f] allyllic esters, [7i] and enoates.[7k] However,Cu-catalyzed borylative coupling of unsaturated hydrocarbon substrates and imines is less developed.[8] Conjugated dienes and especially 1,3-dienes,asacommon feedstock, are ideal nucleophilic allyl metal precursors [9] and readily participate in allylic transformations of carbonyls and imines.[10] We envisioned merging the borylcupration of ac onjugated diene [11] (Scheme 1, step A) and enantioselective imine allyl ation (Scheme 1, step B) in the presence of as uitable chiral copper catalyst. This approach could afford useful homoallylic amines containing an easily derivatizable boron motif.In this method, possible complications include the undesired borylation of imines, [12] poisoning of the metal catalyst by imines or products,a nd difficulty in controlling the regio-(linear vs.b ranched products) [7k,11a] and stereoselectivity (enantio-and/or diastereoselectivity).To test the feasibility of our proposed transformation, we chose acomplex of CuCl and chiral sulfoxide-phophine (SOP, L1)[7j] as acatalyst in preliminary experiments.Inthe presence of isoprene (5 equiv), 1.5 equiv of B 2 (pin) 2 ,a nd NaO...

Cu‐Catalyzed Enantioselective Reductive Coupling of 1,3‐Dienes and Carboxylic Acid Anhydrides

“…Reactions performed in other solvents could evidently diminish the yield (entries 12–14). It is noteworthy that only 1,4‐addition product was detected in the reaction, which is different from the previous work on Cu‐catalyzed borylative coupling of 1,3‐dienes with electrophiles that formed 3,4‐addition products exclusively, [11e–g,14] indicating that the allyl‐Cu complex generated from 1,3‐diene and participated in the anhydride addition step is different from that in those reports. In addition, the configuration of alkene in 3 a is exclusively Z , which is different from those generated from reactions of 1,3‐dienes with aldimines [12] …”

Copper(I)‐Catalyzed Enantio‐ and Diastereodivergent Borylative Coupling of Styrenes and Imines

“…[4] Another important approach is catalytic borylative coupling of alkenes and imines,w here C À Ba nd C À Cb onds are formed in one operation. [5][6][7] TheP rocter group [8] and Cao,L iao,a nd coworkers [9] independently developed acopper-catalyzed enantio-and diastereoselective borylative coupling of allenes or dienes with aldimines to provide g-boryl amine derivatives (Scheme 1a,b). Hoveyda and co-workers reported coppercatalyzed borylative difucntionalization of allenes applicable to N-H ketimines (Scheme 1c).…”

Copper‐Catalyzed Borylative Couplings with C−N Electrophiles

“…In 2016, Cao, Liao, and co‐workers [31] reported the copper‐catalyzed diastereo‐ and enantioselective borylative coupling of imines 26 and dienes 27 . Following in situ oxidation, 1,3‐amino alcohols 28 were obtained (Scheme 7 A).…”