Organo[2-(hydroxymethyl)phenyl]dimethylsilanes as Mild and Reproducible Agents for Rhodium-Catalyzed 1,4-Addition Reactions

Abstract

Stable and reusable tetraorganosilicon reagents, alkenyl-, aryl-, and silyl[2-(hydroxymethyl)phenyl]dimethylsilanes, undergo 1,4-addition reactions to alpha,beta-unsaturated carbonyl acceptors under mild rhodium-catalysis. The reaction tolerates a diverse range of functional groups and is applicable to gram-scale synthesis. Use of a chiral diene ligand allows the achievement of the corresponding enantioselective transformations using the tetraorganosilicon reagents, providing the silicon-based approach to optically active ketones and substituted piperidones that serve as synthetic intermediates of pharmaceuticals. A rhodium alkoxide species is suggested to be responsible for a transmetalation step on the basis of the observed kinetic resolution of a racemic chiral phenylsilane in the enantioselective 1,4-addition reaction under the rhodium-chiral diene catalysis.

Rhodium‐ and Palladium‐Catalyzed Asymmetric Conjugate Additions

“…Scheme 1.43) [188]. Based on the seminal studies of Hudrilk [189,190], Hiyama and Nakao introduced the stable and reusable tetraorganosilicon reagents, alkenyl-, aryl-, and silyl [2-(hydroxymethyl)phenyl]dimethylsilanes 140, which undergo 1,4-addition reactions to α,β-unsaturated carbonyl acceptors under mild rhodium catalysis (Scheme 1.54) [153,[191][192][193]. The only byproduct in this case was the volatile cyclic siloxane 141.…”

“…This reagent enables the introduction of a large gamut of aryl and alkenyl groups onto all α,β-unsaturated ketones, ester, amides, nitriles, vinylogous amides, fumarates, and maleimides (Scheme 1.54) [192]. Chiral diene ligands L28 are extremely effective for this transformation, using the tetraorganosilicon reagents 140.…”

“…The aryl derivative of reagent 140a can be easily regenerated by addition of the corresponding Grignard reagent onto 141, whereas the alkenyl functionalized 140b is obtained by reduction of 141 by LiAlH 4 followed by protection and subsequent regioselective alkyne hydrosilylation and deprotection (Scheme 1.55) [193]. The silyl variant (142) of reagent 140 can also function as a silyl transfer, albeit with only moderate yield due to competitive loss of silane [192]. In addition to aryl and alkenyl groups, bis(pinacolato)diboron (25) and silyl boronic ester 26 can be used in Rh-cat conjugate additions to transfer boron [49] and silyl groups respectively.…”

Palladium‐Catalyzed Silylation of Electron‐Deficient Aryl Iodides Using Triorganosilane in the Presence of Pyridine and LiCl

“…Our next interest was focused on the formation of aryl[2-(hydroxymethyl)phenyl]dimethylsilanes, which recently were reported to be excellent aryl donors for various transitionmetal-catalysed reactions. [4] The THP-protected [2-(hydroxymethyl)phenyl]dimethylsilane was treated with 4-iodobenzonitrile (5a) and 4-iodoacetophenone (5b) followed by the treatment with p-TsOH to remove THP protective group, and the silylated arenes 10 and 11 were obtained in 59 % and 58 % yields, respectively. The [2-(hydroxymethyl)-phenyl]silylated acetophenone 11 was then treated with cyclohexenone in the presence of a rhodium catalyst which gave the 1,4-adduct 12 in 96 % yield (Scheme 1).…”

Enantioselective synthesis of (R)-isocarvone from (S)-perillaldehyde

“…7 Theodorakis and coworkers have recently reported the first synthesis of isocarvone (in both enantiomerically pure forms) using an enantiodivergent approach, starting from monoterpene carvone. 7 Nakao and co-workers, 17 in their reported results on the enantioselective 1,4-addition of tetraorganosilicon reagents under the rhodium-chiral diene catalysis to α,β-unsaturated carbonyl acceptors, have prepared (R)-3-isopropenylcyclohexanone (4a) with a high enantiomeric excess (96 %) from cyclohexen-2-one. The higher saturated 3-isopropylcyclohexanone (4b) can be prepared more easily with a high yield and enantiomeric excess by catalytic 1,4-addition of organometallic reagents to cyclohexenone, 18 by organocatalytic asymmetric transfer hydrogenation of 3-isopropyl-2-cyclohexenone 19 or by a chemoenzymatic process.…”