Enantioselective Synthesis of Multisubstituted Allenes by Cooperative Cu/Pd‐Catalyzed 1,4‐Arylboration of 1,3‐Enynes

Abstract

A cooperative Cu/Pd‐catalyzed enantioselective synthesis of multisubstituted allenes is established. By employing chiral sulfoxide phosphine (SOP)/Cu and PdCl2(dppf) complexes as catalysts, the 1,4‐arylboration of 1,3‐enynes provides an efficient approach to trisubstituted chiral allenes with up to 92 % yield and 97:3 er. Furthermore, by using 2‐substituted 1,3‐enynes as substrates, the tetrasubstituted chiral allenes were successfully generated using this strategy. Finally, theoretical calculations indicate that the transmetallation of the allenylcopper species is the rate‐limiting step of this transformation.

Copper‐Catalyzed Asymmetric Coupling of Allenyl Radicals with Terminal Alkynes to Access Tetrasubstituted Allenes

“…[9] Moreover, most of these methodologies rely on substrates with particular polar functional groups and/or kinetic resolution processes, which arguably impedes their wide applications in organic synthesis. [8,9] Therefore, the development of robust catalysts to achieve the enantiocontrol over allenyl radical species for the expedient assembly of diverse tetrasubstituted chiral allenes is still highly desirable.…”

“…[4,5] On the other hand, axially chiral allenes not only are important structural motifs in natural products, bioactive molecules, and functional materials, but also serve as versatile synthons, ligands, and catalysts in organic synthesis. [6] In this context, although many elegant strategies have been described for the synthesis of chiral diand trisubstituted allenes, [7] only a limited number of approaches have been reported for the synthesis of tetrasubstituted chiral allenes based on metal catalysis [8] and organocatalysis. [9] Moreover, most of these methodologies rely on substrates with particular polar functional groups and/or kinetic resolution processes, which arguably impedes their wide applications in organic synthesis.…”

“…Thus, we next examined the more electron-rich N,N,P-tridentate ligand L5 and found that the reaction provided product 4 in 61 % yield, along with the cross-coupling and alkyne 1,2-carboalkynylation side products from 2 a and 3 a (Scheme 2 and Table S1, entry 6). [14] We then evaluated a series of chiral cinchona alkaloid-derived N,N,P-ligands (L6-10) with diverse substituents at different positions of the P-phenyl rings and found that L10 with an isopropyl group on the ortho position proved to be the best (Scheme 2 and Table S1, entries [7][8][9][10][11]. The ratios of starting materials also affected the ratio between the desired product and side products and the reaction of 1 a, 2 a, and 3 a in a molar ratio of 1.5:1.2:1.0 gave the sole product 4 with excellent enantioselectivity (Table S1, entry 12).…”

Beyond Carbon: Enantioselective and Enantiospecific Reactions with Catalytically Generated Boryl- and Silylcopper Intermediates

“…Since the seminal reports by Liao and Brown, continuous efforts in enantioselective borylative arylation reactions have been made to extend the scope of available substrates beyond alkenylarenes, 131 , 132 such as alkenylheteroarenes, 133 cyclic 1,3-dienes, 134 and 1,3-enynes. 135 …”

“…Aside from the reaction of α-alkoxyalkylcopper intermediates with ketones and imines, these can also be further processed in a palladium-catalyzed stereospecific cross-coupling cycle similar to the aforementioned dual catalysis ( Scheme 8 ). 129 − 135 The same research group disclosed another enantioselective reductive coupling of aldehydes and aryl or allyl electrophiles using a chiral copper–NHC catalyst and a palladium–bisphosphine catalyst whereby enantioenriched secondary silyl ethers were readily accessed ( Scheme 11 , bottom). 140 Aryl bromides and allyl carbonates participated in the reaction under different optimized setups with good enantiocontrol.…”