A Broadly Applicable NHC–Cu-Catalyzed Approach for Efficient, Site-, and Enantioselective Coupling of Readily Accessible (Pinacolato)alkenylboron Compounds to Allylic Phosphates and Applications to Natural Product Synthesis

Abstract

A set of protocols for catalytic enantioselective allylic substitution (EAS) reactions that allow for additions of alkenyl units to readily accessible allylic electrophiles is disclosed. Transformations afford 1,4-dienes that contain a tertiary carbon stereogenic site and are promoted by 1.0–5.0 mol % of a copper complex of an N-heterocyclic carbene (NHC). Aryl- as well as alkyl-substituted electrophiles bearing a di- or trisubstituted alkene may be employed. Reactions can involve a variety of robust alkenyl–(pinacolatoboron) [alkenyl–B(pin)] compounds that can be either purchased or prepared by various efficient, site-, and/or stereoselective catalytic reactions, such as cross-metathesis or proto-boryl additions to terminal alkynes. Vinyl-, E-, or Z-disubstituted alkenyl-, 1,1-disubstituted alkenyl-, acyclic, or heterocyclic trisubstituted alkenyl groups may be added in up to >98% yield, >98:2 SN2′:SN2, and 99:1 enantiomeric ratio (er). NHC–Cu-catalyzed EAS with alkenyl–B(pin) reagents containing a conjugated carboxylic ester or aldehyde group proceed to provide the desired 1,4-diene products in good yield and with high enantioselectivity despite the presence of a sensitive stereogenic tertiary carbon center that could be considered prone to epimerization. In most instances, the alternative approach of utilizing an alkenylmetal reagent (e.g., an Al-based species) represents an incompatible option. The utility of the approach is illustrated through applications to enantioselective synthesis of natural products such as santolina alcohol, semburin, nyasol, heliespirone A, and heliannuol E.

Catalytic diastereo- and enantioselective additions of versatile allyl groups to N–H ketimines

“…Enantioselectivity was considerably higher compared to the closely related N -mesityl-substituted variant ( 7a ; see below for mechanistic analysis). Additionally, while sulfonate-containing NHC–Cu catalysts have been used for enantioselective allylic substitutions 26,27 and conjugate additions 28,29,30 , none emerged as optimal for a 1,2-addition.…”

Enhanced π‐Back‐Donation as a Way to Higher Coordination Numbers in d10 [M(NHC)n] Complexes: A DFT Study

“…[1d,g, 3] In stark contrast, [Ni(iPr 2 Im) 2 ]( iPr 2 Im = 1,3-diisopropyl-imidazolin-2-ylidene) activates CÀFb onds, which are the strongest carbonÀelement bonds, in perfluoroaromaticsa tr oom temperature and even mediates the Suzuki-Myaura couplingr eaction of fluoroorganics with arylboronic acids. [4] Besides the widely appliedN HC complexes of Ni 0 and Pd 0 ,d 10 copper(I)-and gold(I)-based NHC complexes are also gaining increased attention as catalytic species, [5] and this area has recently been extended to Group12 metals as well, for example, in borylation reactions. [6] Interestingly,t he great majority of isolated d 10 [M(NHC) n ] complexes is mainly limited to di-coordinated fourteen valence electron (VE) ML 2 species of Group 10 and 11 elements, and mercury(II).…”

Coinage Metal Complexes of Chiral N‐Heterocyclic Carbene Ligands: Syntheses and Applications in Asymmetric Catalysis

“…Furthermore, Cu(I) complexes of chiral NHC ligands of 6 and 8 were involved in enantioselective allylic substitutions involving alkenyl nucleophiles. However, the combination of CuCl and imidazolinium derivative 9 or 10 as promising catalyst resulted in an enantioselective allylic substitution to give acetal‐containing alkenyl‐B(pin) . Furthermore, analogues studies by Hoveyda et al.…”