Synthesis of Enantioenriched Allylic Silanes via Nickel-Catalyzed Reductive Cross-Coupling

Abstract

An asymmetric Ni-catalyzed reductive cross-coupling has been developed to prepare enantioenriched allylic silanes. This enantioselective reductive alkenylation proceeds under mild conditions and exhibits good functional group tolerance. The chiral allylic silanes prepared here undergo a variety of stereospecific transformations, including intramolecular Hosomi-Sakurai reactions, to set vicinal stereogenic centers with excellent transfer of chirality.

Enantioconvergent Cross‐Couplings of Alkyl Electrophiles: The Catalytic Asymmetric Synthesis of Organosilanes

“…We have been interested in expanding the scope of enantioconvergent cross‐couplings to include electrophiles that lack either of the features illustrated in A and B (Figure ). An example of such an electrophile is α‐halosilane C , enantioconvergent cross‐coupling of which would provide chiral organosilanes. Chiral organosilanes (e.g., 1 and 2 ) are of interest in fields such as medicinal chemistry as replacement of carbon with silicon can lead to improved pharmacological properties (e.g., enhanced lipophilicity and potency) without element‐specific toxicity due to the presence of silicon; to date, there are limited methods for the direct catalytic asymmetric synthesis of such organosilanes .…”

Enantioselective Construction of α‐Chiral Silanes by Nickel‐Catalyzed C(sp3)−C(sp3) Cross‐Coupling

“…[9] Just recently,R eisman and co-workers achieved the same bond formation by an elegant reductive cross-coupling of racemic a-silylated benzyl chlorides and vinyl bromides (Scheme 1, top). [10] These reactions generate highly enantioenriched allylsilanes.O fc ourse,t hese can be converted into alkylsilanes by hydrogenation but methods for the direct construction of simple a-chiral alkylsilanes with no functional group in the proximity of the asymmetrically substituted carbon atom are rare. [11] Encouraged by the state of the art of enantioselective transition-metal-catalyzed C(sp 3 )ÀC(sp 3 ) couplings of racemic alkyl electrophiles and carbon nucleophiles, [12,13] we embarked on the elaboration of ap rocedure that enables enantiocontrolled bond formation between a-silylated alkyl iodides (= a-iodo alkylsilanes) and alkylzinc reagents (Scheme 1, bottom).…”

Nickel‐Catalyzed Conversion of Enol Triflates into Alkenyl Halides

“…Having identified satisfactory reaction conditions, the substrate scope of the Ni-catalyzed halogenation reaction was investigated ( Table 2). The halide exchange was found to be compatible with a variety of common functional groups, including amines (4), carbamates (5, 13), pyridines (20), alkenes (12), dienes (10,14), esters (19), ketals (6, 14), and enones (11). Chemoselective halogenation of alkenyl triflates was observed in preference to aryl triflates (15, 20), aryl chlorides (9, 21), and aryl boronates (22); however, competitive halide exchange was observed in the presence of aryl bromides and iodides.…”