Asymmetric Synthesis of Borylalkanes via Copper-Catalyzed Enantioselective Hydroallylation

Abstract

An efficient synthetic method for preparing enantioenriched secondary borylalkanes has been achieved through a copper-catalyzed regio- and enantioselective hydroallylation of alkenyl boronates and boramides employing hydrosilanes and allylic phosphates. In the presence of a copper catalyst with a chiral Walphos ligand, a range of alkenylboron compounds with an aryl, heteroaryl, or alkyl substituent produced secondary homoallylic alkylboron compounds in good yields and with high enantioselectivities up to 99% ee. The utility of the resulting alkylboronates was demonstrated in an efficient synthesis of (S)-massoialactone.

Recent Advances in Hydrometallation of Alkenes and Alkynes via the First Row Transition Metal Catalysis

“…[59] Scheme 17 Cu-H catalyzed hydroalkylation reported by Lalic In 2017, Ge and co-workers described an enantioselective copper-catalyzed hydroarylation of styrenes with quinoline N-oxides, affording chiral 2-alkyl quinolines as the products (Scheme 18a). [61] Scheme 18 Cu-H catalyzed hydroarylation In 2016, Yun and co-workers reported a copper-catalyzed asymmetric hydroallylation of alkenyl boronates with a chiral bisphosphine ligand (17), providing a synthetic method for the preparation of enantioenriched allylic substituted alkylboron compounds (Scheme 19a). [61] Scheme 18 Cu-H catalyzed hydroarylation In 2016, Yun and co-workers reported a copper-catalyzed asymmetric hydroallylation of alkenyl boronates with a chiral bisphosphine ligand (17), providing a synthetic method for the preparation of enantioenriched allylic substituted alkylboron compounds (Scheme 19a).…”

Versatile Homoallylic Boronates by Chemo‐, SN2′‐, Diastereo‐ and Enantioselective Catalytic Sequence of Cu−H Addition to Vinyl‐B(pin)/Allylic Substitution

“…[10] While this manuscript was being prepared, reactions involving ( E )-1,2-disubstituted alkenyl–B(pin) substrates and allylphosphate with bis-phosphine–Cu catalysts were disclosed (to generate products with a single stereogenic center); [11] processes were highly enantioselective but the only reported case with an ( E )-1,2-disubstituted allylic phosphate furnished the desired product in 78:22 diastereomeric ratio (d.r.) and 73:27 enantiomeric ratio (e.r.…”

“…and e.r. This was somewhat surprising since chiral phosphines – and some of these exact ligands – have been shown to be optimal in several transformations that begin with enantioselective Cu–H addition to an alkene ( phos-2 , [13] phos-3 , [11] and phos-6 [6f–h] ). We took these findings as an indication that the desired sequence of reactions demands a distinct set of catalysts.…”

Ligand‐Controlled Regiodivergent and Enantioselective Copper‐Catalyzed Hydroallylation of Alkynes

“…In this context, an attractive protocol for using stable and readily available olefins or alkynes as the latent carbon nucleophiles, in lieu of preformed organometallic reagents,b ym eans of hydrometalation processes [4] for coupling with electrophiles, has gained tremendous attention as it addresses some of the limitations of preformed organometallic reagents.R ecently, in elegant works using an in situ generated copper hydride (CuH) catalyst, [5] Buchwald and co-workers pioneered development of an intermolecular asymmetric reductive coupling reaction of vinylarenes with allylic phosphates,n amely hydroallylation of vinylarenes,t hus furnishing ar ange of bstereocenter-substituted alkenes with excellent enantioselectivities. [7] Meanwhile,t he group of Hoveyda elegantly described an asymmetric hydroallylation reaction of alkenyl boronates with internal allylic phosphates,t hus furnishing afacile method for the synthesis of homoallylic borylalkanes containing two contiguous stereocenters (Scheme 1a). [7] Meanwhile,t he group of Hoveyda elegantly described an asymmetric hydroallylation reaction of alkenyl boronates with internal allylic phosphates,t hus furnishing afacile method for the synthesis of homoallylic borylalkanes containing two contiguous stereocenters (Scheme 1a).…”

“…[15] 1,4-Dienes (skipped dienes) are synthetically versatile functional groups and ubiquitous structural motifs present in aw ide variety of natural products of biological significance and pharmaceutical drugs. Inspired by the recent reports on CuH catalysis, [5][6][7][8][9][10][11][12][13][14] we envisioned that the enantioselective hydroallylation of alkynes might provide an ideal and straightforward method for the preparation of such optically active units. While these methods mainly focused on either the racemic transformations or the use of stereochemically welldefined precursors,t he catalytic asymmetric version remains largely undeveloped.…”