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

Abstract

An enantioselective C(sp 3 ) À C(sp 3 )cross-coupling of racemic a-silylated alkyl iodides and alkylzinc reagents is reported. The reaction is catalyzedb yN iCl 2 /(S,S)-Bn-Pybox and yields a-chiral silanes with high enantiocontrol. The catalyst system does not promote the cross-coupling of the corresponding carbon analogue,c orroborating the stabilizing effect of the silyl group on the alkyl radical intermediate (asilicon effect). Both coupling partners can be,but do not need to be,functionalized, and hence,even a-chiral silanes with no functional group in direct proximityo ft he asymmetrically substituted carbon atom become accessible.This distinguishes the new method from established approaches for the synthesis of a-chiral silanes. Scheme 3. Scope II:V ariation of the alkylzinc bromide. [a] Run at 20 8 8C.Scheme 4. Scope III:V ariation of the substituents at the silicon atom in the a-iodo alkylsilane. Scheme 5. Control experiments. Angewandte Chemie Communications

Ketones from Nickel‐Catalyzed Decarboxylative, Non‐Symmetric Cross‐Electrophile Coupling of Carboxylic Acid Esters

“…[12] Applying these optimized conditions to av ariety of different carboxylic acid pairs demonstrated that the chemistry was useful for the synthesis of dialkyl ketones and aryl alkyl ketones (Table 2). Functional group compatibility included acidic NÀHbonds (14,15,16,35), protected nitrogen atoms (6,13,23,32), and protected alcohols (37, 39). Notably, ap rimary alkyl bromide (9)d id not react with nickel or the nucleophiles present.…”

“…First, while most thioester substrates tested coupled in reasonable yield, reactions with thioesters derived from a-amino acids and 2-picolinic acid were low-yielding.Second, most N-hydroxyphthalimide esters coupled in high yield, but reactions with esters derived from secondary cyclopropyl carboxylic acids,d ifluoroacetic acid, and unstrained tertiary carboxylic acids (such as pivalic acid) were low-yielding.T he secondary cyclopropane limitation could be overcome with the use of an a-silyl group (29), which is easily introduced and removed. [15] Theu se of two different carboxylic acids instead of ac arboxylic acid and an alkyl halide or organometallic reagent has several notable advantages.F irst, the large number of carboxylic acids makes new chemical space available:( À)-menthyloxyacetic acid (12), a-amino acids (13,14,15), lithocholic acid (35), and 2,4-D (38)a re readily available as carboxylic acids,b ut their corresponding alkyl halides are not commercially available.Inthe cases where the corresponding alkyl bromides are available,t he cost difference can be significant (greater than 10-fold for 32, 34, see the Supporting Information). Second, because two acids are used, the mode of activation can be swapped to improve yields with little extra synthetic effort (Scheme 2): cyclopropane and adamantane carboxylic acids were best coupled as thioesters (25, 33)and a-amino acid NHP esters provided the best yields (13)(14)(15).…”

“…[15] Theu se of two different carboxylic acids instead of ac arboxylic acid and an alkyl halide or organometallic reagent has several notable advantages.F irst, the large number of carboxylic acids makes new chemical space available:( À)-menthyloxyacetic acid (12), a-amino acids (13,14,15), lithocholic acid (35), and 2,4-D (38)a re readily available as carboxylic acids,b ut their corresponding alkyl halides are not commercially available.Inthe cases where the corresponding alkyl bromides are available,t he cost difference can be significant (greater than 10-fold for 32, 34, see the Supporting Information). Second, because two acids are used, the mode of activation can be swapped to improve yields with little extra synthetic effort (Scheme 2): cyclopropane and adamantane carboxylic acids were best coupled as thioesters (25, 33)and a-amino acid NHP esters provided the best yields (13)(14)(15). This strategy is facilitated by the use of crude esters, formed from the corresponding uronium reagents, [11c,16] instead of purified materials (Scheme 2).…”

Beyond Carbon: Enantioselective and Enantiospecific Reactions with Catalytically Generated Boryl- and Silylcopper Intermediates

“…It is important to note here that α-halo alkylboronates and alkylsilanes were capable of engaging in nickel-catalyzed enantioselective alkyl–alkyl Negishi coupling with alkylzinc bromides, therefore providing fully alkyl-substituted α-chiral boronates and silanes that are of value but were previously unavailable. 158 − 160 …”

Stereospecific and Chemoselective Copper‐Catalyzed Deaminative Silylation of Benzylic Ammonium Triflates

“…[2,6] Our efforts to render these radical reactions enantioconvergent have been fruitless so far. [7] We therefore turned away from alkyl halides and redox-active carboxylic acid derivatives and considered the use of quaternary ammonium salts as electrophiles. [8] These are stable towards light and oxygen and easily accessible in high enantiomeric purity.…”