Copper‐Catalyzed Enantioselective Allylboration of Alkynes: Synthesis of Highly Versatile Multifunctional Building Blocks

Abstract

The first copper‐catalyzed enantioselective allylboration of alkynes is reported. The method employs a multitasking chiral NHC‐Cu catalyst and provides access to densely functionalized molecules from simple starting materials with excellent levels of chemo‐, regio‐, and enantioselectivity. These multifunctional products display highly versatile reactivity as shown by the synthesis of a variety of non‐racemic molecular scaffolds. DFT calculations were conducted to gain insight into the high selectivity levels of this catalytic process.

Enantio‐ and Diastereoselective Copper‐Catalyzed Allylboration of Alkynes with Allylic gem‐Dichlorides

“…A different approach relies on the enantioselective allylic substitution of the catalytically generated organocopper intermediate, as described by Hoveyda in the borylative coupling between allenes and allylic phosphates (Scheme 1b) [6] . We recently applied this strategy to the copper‐catalyzed asymmetric allylboration of alkynes which involves the regio‐ and enantioselective coupling of an allylic bromide with a catalytically generated β‐boryl‐substituted alkenylcopper intermediate (Scheme 1c) [7, 8] . Realizing that the presence of two chlorine atoms in an allylic gem ‐dichloride might result in a dual role as leaving group and as a stereocontrol element, we envisaged that an asymmetric alkyne allylboration reaction based on this type of allylic substrates might lead to an unprecedented degree of complexity in which two new stereodefined olefins and a bis‐allylic stereocenter would be created in a single step (Scheme 1d).…”

Copper‐Catalyzed Preparation of Alkenylboronates and Arylboronates

“…Then in 2019, Fananas-Mastral Group employed a sulfonate-bearing chiral NHC ligand (L30b)-CuCl catalyst to achieve first enantioselective allylboration of alkynes with allylic bromides and B 2 pin 2 to access chiral 1,4-dienes with excellent degrees of chemo-, regio-, and enantioselectivity under mild conditions. [139] Terminal arylalkynes were found more reactive than diphenylacetylene and 1-hexyne. The E/Zconfiguration of the allylic substrates influenced the enantioselectivity of the allylboration reaction, (E)-substrate offered better results compare to (Z)-1,4-dichloro-2-butene.…”

Sulfonate N‐Heterocyclic Carbene–Copper Complexes: Uniquely Effective Catalysts for Enantioselective Synthesis of C−C, C−B, C−H, and C−Si Bonds

“…In 2019, Fañanás‐Mastral outlined a process involving a terminal alkyne, an allylic bromide, and B 2 (pin) 2 , catalyzed by a complex derived from imid(S)‐1 a (Scheme 27). [57] Reactions with aryl‐ and alkenyl‐substituted alkynes were efficient, and an example of a cyclopropyl alkyne was provided, but a transformation with an n ‐alkyl‐bearing acetylene was minimally regioselective. Synthesis of formyl‐substituted vinyl cyclopropane demonstrates versatility.…”

“…That is, as a result of interaction with Cu during π‐allyl formation, Cα is closer to the ligand than the Me group (Cα‐Cu=2.63 Å vs. C Me ‐Cu=3.06 Å). DFT studies by Fañanás‐Mastral [57] ( XXXI – XXXII , Scheme 36 c) indicate that a S=O⋅⋅⋅Na⋅⋅⋅Br bridge might well be responsible for the high e.r. in the corresponding multicomponent reactions (see Scheme 27).…”