No abstract

This review covers the synthesis of isolabile vinylmetalloids through hydroboration, hydrosilylation, and hydrostannation, with special focus on recent developments, metal-catalyzed reactions, and synthetically useful methods.

The complex [Cp*Ru(MeCN) 3 ]PF 6 is shown to catalyze the hydrosilylation of a wide range of alkynes. Terminal alkynes afford access to α-vinylsilane products with good regioselectivity. Deuterium labeling studies indicate a clean trans addition process is at work. The same complex is active in internal alkyne hydrosilylation, where absolute selectivity for the trans addition process is maintained. Several internal alkyne substrate classes, including propargylic alcohols and α,β-alkynyl carbonyl compounds, allow regioselective vinylsilane formation. The tolerance of a wide range of silanes is noteworthy, including alkyl-, aryl-, alkoxy-, and halosilanes. This advantage is demonstrated in the direct synthesis of triene substrates for silicon-tethered intramolecular DielsAlder cycloadditions.Metal-catalyzed simple addition reactions of alkynes are important synthetic processes and are desirable from the standpoint of synthetic efficiency and atom economy. Questions of regioand stereoselectivity become important considerations, and pathways affording syn addition are plentiful and well studied. Metal catalysis of trans addition processes-where new bonds must be formed on opposite sides of the alkyne-have only rarely been observed. Indeed, the possibility of creating direct trans addition processes which do not involve initial cis addition followed by E/Z isomerization is an exciting target. This paper describes our work studying trans addition processes in alkyne hydrosilylation with ruthenium catalysts to afford vinylsilane products.Vinyl-metal species are extremely important building blocks in organic synthesis. 1,2 Among these, vinylsilanes play a growing role due to their low cost, low toxicity, ease of handling, and simplicity of byproduct removal. Particularly significant is the potential of vinylsilanes as nucleophilic partners in palladium-catalyzed cross-coupling reactions. 3 Vinylsilanes are also useful as acceptors in conjugate addition reactions, as masked ketones through Tamao-Fleming oxidation, 4 and as terminators for cation cyclizations. 5 Unlike most other organometallic reagents-including in many cases organoboranes and organostannanes-vinylsilanes can be readily carried through many synthetic operations.However, the utility of vinylsilanes has been inhibited by the inconvenience of accessing stereo-and regio-defined vinylmetal compounds. Among the possible routes to these compounds, hydrosilylation of alkynes represents the most straightforward, atom-economical access. 6 Classical platinum catalysis 7 provides clean cis addition to (E)-vinylsilanes (2), and ligand tuning has made this a very regioselective process as well. 8 In addition, there has been significant progress using a variety of metal-catalyzed approaches to provide stereodefined, 1,2-substituted vinylsilanes of the form 1 or 2. There has been no reported general access to bmtrost@stanford.edu. NIH Public Access NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscript 1,1-disubstituted vinylsilanes 9 (3) a...

No abstract

The combination of peptide molecular recognition and residue-selective dirhodium catalysis allows modification of aromatic side chains that is selective for coil structures. A rate enhancement of >10(3) relative to nonselective dirhodium modification was observed. The increased reactivity of this approach creates the first selective chemical modification of the phenylalanine residue.

Coiled-coil assembly of substrate peptides with dirhodium metallopeptide catalysts enables side-chain modification on the basis of molecular shape. A wide range of amino acids are effectively modified, including the first examples of carboxamide (glutamine and asparagine) modification. The method is used to achieve covalent modification of the c-Fos bZip domain at different residues, depending on the metallopeptide structure. By combining promiscuous catalytic reactivity with specific molecular recognition, this work establishes a general strategy for protein modification on the basis of molecular shape. A broad range of peptide-protein interactions are potentially amenable to this approach.

Density functional calculations have been carried out to understand the anti-addition stereochemistry and Markovnikov regiochemistry of the hydrosilylation of terminal alkynes and the endo-dig product of intramolecular hydrosilylation of homopropargyl alcohols catalyzed by cationic cyclopentadienyl-ruthenium complexes. It has been found that hydride or silyl insertion is concerted with the oxidative addition of the H-Si bond. Hydride insertion is much more favorable than silyl insertion. Such a hydride insertion nicely reproduces the observed regioselectivity, while silyl insertion would predict the opposite result. The hydride insertion leads to the formation of a eta(2)-vinylruthenium intermediate for the reaction of acetylene or a metallacyclopropene intermediate for the reaction of propyne. In the formation of both intermediates, there is a C(alpha)-C(beta) bond rotation so that the transferring hydride becomes anti to the silyl group. This is followed by a facile reductive alpha-silyl migration transition state, which results in the overall anti-addition stereochemistry. The proposed mechanism also rationalizes the observed regio- and stereochemistry of the intramolecular reaction.

In this study, we present advances in the use of rhodium(II) metallopeptides for protein modification. Site-specific, proximity-driven modification is enabled by the unique combination of peptide-based molecular recognition and a rhodium catalyst capable of modifying a wide range of amino-acid side chains. We explore catalysis based on coiled-coil recognition in detail, providing an understanding of the determinants of specificity and culminating in the demonstration of orthogonal modification of separate proteins in cell lysate. In addition, the concepts of proximity-driven catalysis are extended to include modification of the natural Fyn SH3 domain with metallopeptides based on a known proline-rich peptide ligand. The development of orthogonal catalyst-substrate pairs for modification in lysate, and the extension of these methods to new natural protein domains, highlight the capabilities for new reaction design possible in chemical approaches to site-specific protein modification.