NHC‐Cu‐Catalyzed Enantioselective Hydroboration of Acyclic and Exocyclic 1,1‐Disubstituted Aryl Alkenes

Abstract

We recently discovered that hydroboration of 1,2-disubstituted aryl olefins can be catalyzed by chiral Cu-based bidentate N-heterocyclic carbene (NHC) [1] complexes. [2, 3] Reactions proceed to deliver homobenzylic CÀB bonds exclusively, [4] which is in contrast to transformations with alkylboranes or those catalyzed by the more costly Rh-or Irbased complexes, where formation of benzylic C À B bonds is preferred.[3] We later showed that the NHC À Cu-catalyzed transformations proceed efficiently with b-vinylboronates to afford acyclic vicinal diboronates with complete site selectivity (< 2 % geminal).[5] The above protocols are enantioselective, delivering boron-substituted stereogenic centers at secondary carbon atoms in 86:14-99:1 enantiomeric ratio (e.r.). Despite such advances, as well as seminal findings reported by other research groups, [3] several shortcomings persist. One long-standing problem relates to catalytic enantioselective hydroborations of 1,1-disubstituted alkenes.[6] The use of stoichiometric quantities of chiral boranes in reactions of 1,1-disubstituted alkenes has been outlined; [7] however, high enantioselectivity (e.r. > 90:10) is only observed when there is a significant size difference between the olefin substituents. Rh-and Ir-catalyzed processes with catecholborane typically furnish low enantioselectivity with 1,1-disubstituted alkenes and, in some cases, control of site selectivity is problematic. [8] Recently, an Ircatalyzed process with pinacolatoborane was found to afford complete site selectivity and e.r. ! 90:10 in the case of two amethylstyrene derivatives (overall range of e.r. = 66:34-96:4).[9] Herein, we present an NHCÀCu-catalyzed process for the site-and enantioselective catalytic hydroboration of 1,1-disubstituted aryl olefins (Scheme 1);[10] a-alkyl-b-pinacolatoboranes are formed with > 98 % site selectivity, in up to > 98 % yield and e.r. = 96.5:3.5. Reactions involving a range of acyclic 1,1-disubstituted aryl olefins, including those that contain alkyl substituents other than the typically utilized methyl unit, have been developed. Also included are transformations of exocyclic alkenes, which, to the best of our knowledge, have not been previously reported.In considering the mechanism of catalytic 1,1-disubstituted alkene hydroborations (Scheme 1), we surmised that transformations would likely be initiated by [(NHC)Cu{B-(pin)}][11] i [formed from reaction of bis(pinacolato)diboron (1) with an NHC-Cu-alkoxide]. Subsequent Cu À B addition would afford b-alkylborane ii, which contains a quaternary Cu-substituted stereogenic center. Protonation of the CuÀC bond, [12] likely occurring with retention of configuration, [4] can deliver the desired product and regenerate iii, which reacts with 1 to form i. An uncommon feature of the catalytic processes is that the eventual stereochemical outcome does not depend only on the enantioselectivity of the Cu À B addition: the stereochemistry of the intermolecular protonation of the enantiomerically enriched alkylcopper species wit...

Copper–NHC complexes in catalysis

“…Despite these encouraging results, the 1,1-disubstitued aryl olefins did not proceed the same way and a change of catalyst was required to achieve this transformation. In the particular case of allylic alcohols, the 2-substituted allylboronates were formed, which is correlated to the fast rate of the Cu-alkoxide elimination vs the Cu-C protonation [42]. Recently,…”

Synthesis of Secondary and Tertiary Alkylboranes via Formal Hydroboration of Terminal and 1,1-Disubstituted Alkenes

“…9 Alkenes such as styrenes provide an electronic bias for the development of catalyst-substrate interactions that enable regioselectivity reversals, with notable illustrations in directly accessing benzylic boranes from the rhodium-catalyzed hydroboration of styrenes. 10 The copper-catalyzed addition of bis(pinacolato)diboron (B 2 Pin 2 ) in the presence of methanol has been utilized by Hoveyda as a formal hydroboration of terminal alkynes with regioreversal compared with traditional strategies, 11 whereas styrenes afforded the terminal borane product. 11b The procedure, which involves borylmetalation followed by protonation of the resulting Cu-C bond, provides considerable utility as a means to access the more hindered alkenylborane products.…”

Enantioselective 1,1-Arylborylation of Alkenes: Merging Chiral Anion Phase Transfer with Pd Catalysis

“…1 Accordingly, there has been significant interest in developing new enantioselective methods that afford these motifs. Examples of catalytic enantioselective hydroboration, 2 allylic borylation, 3 conjugate borylation, 4 reductive transformations of vinyl boronates 5 and 1,2-diborylation of aromatic imines and styrenes have been reported. 6 Furthermore, several enantioselective borylation reactions utilizing stoichiometric amounts of chiral auxiliaries have been disclosed.…”