Copper‐Catalyzed Borylative Cross‐Coupling of Allenes and Imines: Selective Three‐Component Assembly of Branched Homoallyl Amines

Abstract

Ac opper-catalyzed three-component coupling of allenes,b is(pinacolato)diboron, and imines allows regio-, chemo-, and diastereoselective assembly of branched a,bsubstituted-g-boryl homoallylic amines,t hat is,products bearing versatile amino,a lkenyl, and borane functionality.A lternatively,c onvenient oxidative workup allows access to asubstituted-b-amino ketones.Acomputational study has been used to probe the stereochemical course of the cross-coupling.Branched amines are common motifs in biologically active molecules.S ubstituted homoallylic amines are privileged synthetic precursors to such motifs in addition to being acommon substructure in bioactive synthetic targets in their own right (Scheme 1a).[1] While the allylation of imines provides the most direct access to important homoallylic amines, [2,3] theprocess is generally more challenging than the allylation of aldehydes because of the lower electrophilicity/ reactivity of imines and their increased steric bulk, difficulties in predicting the stereochemical outcome of additions,a nd imine/enamine E/Z isomerization. In particular,the additions of substituted allyl metals require sophisticated levels of regio-and stereocontrol, which, if unchecked, lead to complex mixtures.[4] Thus,n ew approaches to the selective generation and controlled addition of functionalized allyl metals,formed under catalytic conditions using inexpensive catalysts,t o imines,p romises to expand access to complex homoallylic amines while unlocking new avenues for their subsequent synthetic manipulation.Theu se of allenes and imines in catalytic three-component coupling reactions which involve the in situ generation of allyl metals has emerged as an exciting strategy to afford valuable,substituted homoallylic amines (Scheme 1b). [5][6][7] For example,t he groups of Oshima, [5e] Grigg, [5a-d] and have studied the catalytic generation of allyl metals from allenes,byorganometallic addition, and their addition to imines.I na ni mportant advance,M orken and co-workers described the asymmetric palladium-catalyzed diboration of allenes with subsequent addition of an imine to trap the functionalized allyl borane intermediates in as eparate operation.[5j] In the study from Morken et al.,linear adducts were obtained and products were typically isolated as ketones after in situ oxidation of the CÀBb ond. In the above studies, expensive and supply-risk platinum-group metals were used.[5] Herein we describe ar egio-, chemo-, and diastereoselective copper-catalyzed three-component coupling of allenes, [8] bis(pinacolato)diboron, and imines, [9,10] proceeding via allyl coppers to give readily isolable,branched homoallylic amines bearing versatile amino,a lkenyl, and borane functionalities (Scheme 1c).

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

“…[7k] However,Cu-catalyzed borylative coupling of unsaturated hydro-carbon 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.…”

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

“…[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.…”

Copper‐Catalyzed Borylative Couplings with C−N Electrophiles

“…In an effort to circumvent the need for pre‐formed allylmetal reagents in additions to imines, [21] Procter and co‐workers [22] reported the first multicomponent copper‐catalyzed borylative coupling of imines and allenes in 2016. Homoallylic amines 9 were formed from the addition of allylcopper complexes (e.g.…”