H-bonding interactions have been exploited extensively in the design of catalysts for stereoselective synthesis but have rarely been utilized in the development of metal-catalyzed processes. Studies described herein demonstrate that intramolecular H-bonding interactions can significantly increase the rate and levels of stereochemical control in Ru-catalyzed olefin metathesis reactions. The utility of H-bonding in catalytic olefin metathesis is elucidated through development of exceptionally facile and highly diastereoselective ring-opening/cross-metathesis (DROCM) reactions, involving achiral Ru catalysts and enantiomerically enriched allylic alcohols. Transformations proceed to completion readily (> 98% conversion, up to 87% yield), often within minutes, in the presence of < or = 2 mol % of an achiral catalyst to afford synthetically versatile products of high stereochemical purity (up to > 98:2 dr and 11:1 E:Z).

Two new, crystalline solid, storable, and highly enantioselective reagents for aldehyde crotylation have been developed. Both (cis and trans) crotylsilane reagents are easily prepared in bulk, require trivial reaction conditions, and provide the homoallylic alcohol products with near diastereo- and enantiospecificity in many cases.

A highly diastereo- and enantioselective [3 + 2] acylhydrazone-enol ether cycloaddition mediated by a simple chiral silane Lewis acid is described. The reactions are highly practical, as demonstrated by a larger scale (5 g of the hydrazone) reaction in which the product was obtained after recrystallization in 93% yield and 99% ee. Evidence for a stepwise mechanism and a model for the asymmetric induction are presented, as well.

The synthesis, isolation, purification (routine silica gel chromatography), and spectroscopic characterization of high-energy endo stereogenic-at-Ru complex isomers, generated by ring-opening/cross-metathesis (ROCM) reaction of the corresponding exo carbenes, are disclosed. We provide experimental evidence showing that an endo isomer can undergo thermal or Brønsted acid-catalyzed polytopal rearrangement, causing conversion to the energetically favored exo carbene.

A brief synthesis of manzacidin C based on a chiral silane-promoted diastereo- and enatioselective acylhydrazone-alkene [3 + 2] cycloaddition reaction has been achieved. This synthesis is the first synthesis of any of the manzacidins wherein the C(4) and C(6) stereocenters are established in a single highly stereoselective step.