Enzymes that catalyze carbon–silicon bond formation are unknown in nature, despite the natural abundance of both elements. Such enzymes would expand the catalytic repertoire of biology, enabling living systems to access chemical space previously only open to synthetic chemistry. We have discovered that heme proteins catalyze the formation of organosilicon compounds under physiological conditions via carbene insertion into silicon–hydrogen bonds. The reaction proceeds both in vitro and in vivo, accommodating a broad range of substrates with high chemo- and enantioselectivity. Using directed evolution, we enhanced the catalytic function of cytochrome c from Rhodothermus marinus to achieve more than 15-fold higher turnover than state-of-the-art synthetic catalysts. This carbon–silicon bond-forming biocatalyst offers an environmentally friendly and highly efficient route to producing enantiopure organosilicon molecules.

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Give Me an Ar, give Me an N! Arylation of the methyl group in a simple derivative of readily available alanine under palladium catalysis was followed by intramolecular amidation at the same position to give chiral α-amino-β-lactams with a wide range of aryl substituents (see scheme; Phth=phthaloyl). The α-amino-β-lactams were obtained in moderate to high yields with good functional-group tolerance and high diastereoselectivity.

The Pd(II)-catalyzed alkoxylation of unactivated C(sp 3 )-H and C(sp 2 )-H bonds using a new bidentate directing group has been developed. Alkoxylation occurs selectively at the b position with broad substrate scope and high tolerance of functional groups (chloro, cyano, ether, ester, olefin, amino, etc.). Besides alkoxylation of the b-C-H bonds, g-alkoxylation of C(sp 2 )-H bonds could also be achieved, provided that no reactive b-C-H bonds were present. In addition, this DG is readily available and removable.Scheme 1 Pd-catalyzed direct alkoxylation of C-H bonds.

A palladium-catalyzed alkylation of primary and secondary C(sp 3 )-H bonds with alkyl iodides and/or bromides for the synthesis of optically active unnatural a-amino acids (a-AAs) is described. This process is scalable and tolerates a variety of functional groups with complete retention of chirality, providing an efficient new strategy for the synthesis of various unnatural a-amino acid derivatives.Unnatural a-amino acids (a-AAs) are key structural motifs of peptides, peptidomimetics and many other pharmaceutically important compounds. 1 Synthetic derivatives of biologically relevant peptides incorporating unnatural a-AAs oen display interesting pharmacological activity, sometimes with increased potency and enzymatic stability relative to their native counterparts. Apart from this, they have been successfully used as chiral ligands/catalysts and as chiral pool building blocks in asymmetric catalysis and total synthesis. 2 As a consequence, the chemical synthesis of these valuable compounds has received tremendous interests. 3 Traditionally, optically active unnatural a-AAs can be obtained through chemical and enzymatic resolutions of the corresponding racemates or through asymmetric synthesis. However, considering the widespread availability of natural a-amino acids, an attractive approach from the perspectives of atom-and step-economy would be to use them as substrates and perform palladium-catalyzed direct C-H alkylation to access their unnatural counterparts.However, Pd-catalyzed alkylation of unactivated C(sp 3 )-H with alkyl halides remains one of the most difficult transformations in transition-metal-catalyzed C-H functionalization reactions. 4,5 The difficulties of developing such a reaction stem from the following fundamental challenges: [4][5][6] (1) aliphatic C(sp 3 )-H bonds are signicantly more resistant to Pd insertion than C(sp 2 )-H bonds, and it is extremely difficult for the catalyst to distinguish among the many chemically similar C-H bonds on the substrate; (2) alkyl halides are electron-rich and therefore Scheme 1 Pd-catalyzed alkylation of unactivated C(sp 3 )-H bonds.