We report a Rh-catalyzed, enantioselective silylation of arene C–H bonds directed by a (hydrido)silyl group. (Hydrido)silyl ethers that are formed in situ by hydrosilylation of benzophenone or its derivatives undergo asymmetric C–H silylation in high yield with excellent enantioselectivity in the presence of [Rh(cod)Cl]2 and a chiral bisphosphine ligand. The stereoselectivity of this process also allows enantioenriched diarylmethanols to react with site selectivity at one aryl group over the other. Enantioenriched benzoxasiloles from the silylation process undergo a range of transformations to form C–C, C–O, C–I, or C–Br bonds.

We describe an enantioseleclive silylation of cyclopropanes catalyzed by a rhodium precursor and the bisphosphine (S)-DTBM-SEGPHOS. (Hydrido)silyl ethers, generated in situ by the dehydrogenative silylation of cyclopropylmethanols with diethylsilane, undergo asymmetric, intramolecular silylation of cyclopropyl C-H bonds in high yields with high enantiomeric excesses in the presence of the rhodium catalyst. The resulting enantioenriched oxasilolanes are suitable substrates for Tamao-Fleming oxidation to form cyclopropanols with conservation of the ee from the C-H bond silylation. Preliminary mechanistic data suggest that C-H cleavage is likely to be the turnover-limiting and enantioselectivity-determining step.

The functionalization of unactivated C(sp3)-H bonds of aliphatic amines catalyzed by transition-metal complexes is important because amine-based functionality is present in a majority of biologically active molecules and commercial pharmaceuticals. However, such reactions are underdeveloped and challenging to achieve in general because the basicity and reducing properties of alkylamines tends to interfere with potential reagents and catalysts. The functionalization of C-H bonds β to the nitrogen of aliphatic amines to form prevalent 1,2-amino functionalized structures is particularly challenging because the C-H bond β to nitrogen is stronger than the C-H bond α to nitrogen, and the nitrogen in the amine or its derivatives usually directs a catalyst to react at more distal γ- and δ-C-H bonds to form 5- or 6-membered metallacyclic intermediate. The enantioselective functionalization of a C-H bond at any position in amines also has been vexing and is currently limited to reactions of specific, sterically hindered, cyclic structures. We report iridium-catalyzed, β-selective silylations of unactivated C(sp3)-H bonds of aliphatic amines to form silapyrrolidines that are both silicon-containing analogs of common saturated nitrogen heterocycles and precursors to 1,2-amino alcohols by Tamao-Fleming oxidation. These silylations of amines are accomplished by introducing a simple methylene linker between the heteroatom and silicon that has not been used previously for the silylation of C-H bonds. The reactions occur with high enantioselectivity when catalyzed by complexes of new chiral, pyridyl imidazoline ligands, and the rates of reactions with catalysts of these highly basic ligands are particularly fast, occuring in some cases at or even below room temperature.

Several classes of enantioselective silylations of C–H bonds have been reported recently, but little mechanistic data on these processes are available. We report mechanistic studies on the rhodium-catalyzed, enantioselective silylation of aryl C–H bonds. A rhodium silyl dihydride and a rhodium norbornyl complex were prepared and determined to be interconverting catalyst resting states. Kinetic isotope effects indicated that the C–H bond cleavage step is not rate-determining, but the C–H bond cleavage and C–Si bond-forming steps together influence the enantioselectivity. DFT calculations indicate that the enantioselectivity originates from unfavorable steric interactions between the substrate and the ligand in the transition state leading to the formation of the minor enantiomer.

We describe an enantioseleclive silylation of cyclopropanes catalyzed by a rhodium precursor and the bisphosphine (S)-DTBM-SEGPHOS. (Hydrido)silyl ethers, generated in situ by the dehydrogenative silylation of cyclopropylmethanols with diethylsilane, undergo asymmetric, intramolecular silylation of cyclopropyl C-H bonds in high yields with high enantiomeric excesses in the presence of the rhodium catalyst. The resulting enantioenriched oxasilolanes are suitable substrates for Tamao-Fleming oxidation to form cyclopropanols with conservation of the ee from the C-H bond silylation. Preliminary mechanistic data suggest that C-H cleavage is likely to be the turnover-limiting and enantioselectivity-determining step. Graphical Abstract(Hydrido)silyl ethers, generated in situ by the dehydrogenative silylation of cyclopropylmethanols with diethylsilane, undergo asymmetric, intramolecular silylation of cyclopropyl C-H bonds in high yields with high enantiomeric excesses in the presence of a rhodium catalyst. The silylation products are suitable substrates for Tamao-Fleming oxidation to form cyclopropanols with conservation of the ee from the C-H bond silylation.Keywords asymmetric catalysis; C-H activation; cyclopropane; rhodium; silylation The functionalization of C-H bonds with boranes and silanes has been studied intensively, due to the high regioselectivity of these processes for sterically accessible C-H bonds and widespread utility of the products. [1,2] However, the development of enantioselective variants of these reactions, particularly enantioselective functionalization of alkyl C-H bonds, has been limited (Scheme 1). [3][4][5] Kuninobu, Murai and Takai reported the Correspondence to: John F. Hartwig, jhartwig@berkeley.edu. Supporting information for this article is given via a link at the end of the document. HHS Public Access Author ManuscriptAuthor Manuscript Author ManuscriptAuthor Manuscript asymmetric silylation of a C-H bond to generate a stereogenic silicon center with up-to 88% enantiomeric excess (ee) (Scheme 1A). [6,7] Shibata, He, Murai and Takai independently reported the synthesis of planar chiral compounds with moderate to high enantioselectivities by asymmetric C-H silylation of ferrocenes. [8][9][10] Recently, we reported an enantioselective silylation of aryl C-H bonds to form enantioenriched benzoxasilole products with up-to 99% ee. [11] Although these reactions can occur with high enantioselectivity, they are limited to the functionalization of aryl C-H bonds. The only published set of enantioselective silylations of alkyl C-H bonds occurs with low ee (37-40% ee) and with limited scope (Scheme 1B). [12] To create the first silylations of alkyl C-H bonds that occur with high enantioselectivity, we investigated systems for the reactions of cyclopropanes. C-H bonds of cyclopropanes are more reactive than sp 3 C-H bonds of unstrained rings or alkyl chains, [13] and the rigid conformation of a cyclopropane could allow for high stereoselectivity. Yu and co-workers reported enantioselective...