We employ a single catalyst/oxidant system to enable the asymmetric syntheses of indolines, benzodihydrothiophenes, and indanes by C-H insertion of donor/donor carbenes. This methodology enables the rapid construction of densely substituted five-membered rings that form the core of many drug targets and natural products. Furthermore, oxidation of hydrazones to the corresponding diazo compounds proceeds in situ, enabling a relatively facile one- or two-pot protocol in which isolation of potentially explosive diazo alkanes is avoided. Regioselectivity studies were performed to determine the impact of sterics and electronics in donor/donor metal carbene C-H insertions to form indolines. This methodology was applied to a variety of substrates in high yield, diastereomeric, and enantiomeric ratios and to the synthesis of a patented indane estrogen receptor agonist with anti-cancer activity.

Formation of fused pyrazoles via intramolecular 1,3-dipolar cycloadditions of diazo intermediates with pendant alkynes are described. A subsequent thermal [1s, 5s] sigmatropic shift of these pyrazole systems resulted in a ring contraction to form spirocyclic pyrazoles. The limitations of this rearrangement were explored by changing the substituents on the non-migrating aromatic ring and by using substrates lacking an aromatic linkage to the propargyl group.

We employasingle catalyst/oxidant system to enable the asymmetric syntheses of indolines,b enzodihydrothiophenes,a nd indanes by CÀHi nsertion of donor/donor carbenes.T his methodology enables the rapid construction of densely substituted five-membered rings that form the core of many drug targets and natural products.F urthermore,o xidation of hydrazones to the corresponding diazoc ompounds proceeds in situ, enabling ar elatively facile one-or two-pot protocol in which isolation of potentially explosive diazo alkanes is avoided. Regioselectivity studies were performed to determine the impact of sterics and electronics in donor/donor metal carbene C À Hinsertions to form indolines.This methodology was applied to av ariety of substrates in high yield, diastereomeric,and enantiomeric ratios and to the synthesis of ap atented indane estrogen receptor agonist with anti-cancer activity.