Enantio‐ and Diastereoselective 1,2‐Additions to α‐Ketoesters with Diborylmethane and Substituted 1,1‐Diborylalkanes

Abstract

Catalytic enantioselective synthesis of boronate-substituted tertiary alcohols through additions of diborylmethane and substituted 1,1-diborylalkanes to α-ketoesters is reported. The reactions are catalyzed by readily available chiral phosphine–copper(I) complexes and produce β-hydroxyboronates containing up to two contiguous stereogenic centers in up to 99:1 er, and >20:1 dr. The utility of the organoboron products is demonstrated through several chemoselective functionalizations. Evidence indicates reactions occur via enantio-enriched α-boryl-Cu-alkyl intermediate.

Benzyltriboronates: Building Blocks for Diastereoselective Carbon–Carbon Bond Formation

“…4 Alkylboronates, typically synthesized by alkene hydroboration 5 or Miyaura-type borylation of alkyl halides, 6 are likewise valuable reagents for C–C bond formation whose utility will continue to grow as methods for C(sp 3 )–C(sp 3 ) cross coupling mature. 7 Polyboron compounds such as gem -diboronates are beginning to emerge as useful reagents for C–C bond formation as well and have been applied to alkylation reactions, 8 boron–Wittig olefinations, 9 1,2-additions to carbonyls 10 and imines, 11 addition to pyridine- N -oxides, 12 allylic substitution, 13 and enantioselective cross couplings. 14 The use of 1,1,1-alkyltriboronates for C–C bond formation offers similar, if not greater, potential but is less explored and limited to deborylative boron–Wittig olefination 15 or deborylative alkylation (Scheme 1A).…”

(Z)-α-Boryl-crotylboron reagents via Z-selective alkene isomerization and application to stereoselective syntheses of (E)-δ-boryl-syn-homoallylic alcohols

“…It has been shown by Hilt and co-workers that terminal alkenes can undergo transition metal-catalyzed olefin isomerization to give ( Z )-2-alkene isomers with moderate to high selectivity. 11 Inspired by their studies, we decided to pursue a Ni-catalyzed isomerization of 1,1-di(boryl)but-3-ene 1 12 to prepare ( Z )-crotylboronate reagent 2b . As shown in Table 1 , in the presence of 10 mol% of NiCl 2 and dppp, 5 mol% Ph 2 PH, and 20 mol% of Zn and ZnI 2 , isomerization of homoallylboronate 1 did not form any product in CH 2 Cl 2 at –20 °C for 24 h (entry 1, Table 1 ).…”

Catalytic Asymmetric Conjugate Addition of a Borylalkyl Copper Complex for Chiral Organoboronate Synthesis

“…1,1‐Diborylalkanes, which contain two boryl groups at the same sp 3 ‐carbon atom, are attractive reagents for stereoselective C−C coupling reactions with diverse electrophiles owing to the retention of a single boryl moiety even after catalytic activation of one of the C−B bonds . Since the Shibata group first reported the use of 1,1‐diborylalkanes in palladium‐catalyzed chemoselective Suzuki coupling, a number of advances with transition‐metal catalysts were reported (Scheme A, b): enantioselective Suzuki coupling reactions with aryl and vinyl halides, S N 2′‐selective allylic substitution with allylic electrophiles, S N 2 substitution with propagylic electrophiles, and diastereo‐ and enantioselective 1,2‐addition to aldehydes, α‐ketoesters, and imines . However, conjugate addition using 1,1‐diborylalkanes is unknown and remains unexplored.…”