The chromium photocatalyzed cyclopropanation of diazo reagents with electron-rich alkenes is described. The transformation occurs under mild conditions and features specific distinctions from traditional diazo-based cyclopropanations (e.g., avoiding β-hydride elimination, chemoselectivity considerations, etc.). The reaction appears to work most effectively using chromium catalysis, and a number of decorated cyclopropanes can be accessed in generally good yields.

Formal syntheses of tetracyclic terpenoids frondosin B and liphagal are described. Both synthetic routes rely on the use of platinum-catalyzed α,β-unsaturated carbene formation for the key C–C bond forming transformations. The successful route toward frondosin B utilizes a formal (4 + 3) cycloaddition, while the liphagal synthesis features the vinylogous addition of an enol nucleophile as a key step. Both synthetic routes are discussed, revealing insights into structural requirements in the catalytic α,β-unsaturated carbene reaction manifold.

A chromium-catalyzed, visible light-activated net [4 + 2] cycloaddition between dienes and electron-deficient alkenes is described. Gathered evidence, via control experiments, isolated intermediates, and measured redox potentials, points to several converging reaction pathways that afford the cyclohexene adducts, including a photochemical [2 + 2] cycloaddition/vinylcyclobutane rearrangement cascade and a substrate excitation/oxidation sequence to a radical cation intermediate. Notably, the accompanying mechanistic stipulations result in a process that yields regioisomeric compounds from those generated by traditional Diels–Alder cycloadditions.

A synthetic approach to pordamacrine A that features two key transformations is discussed. The first transformation applies an Ireland-Claisen rearrangement to establish sterically congested vicinal carbon centers. Although a hard enolization technique for accessing the silyl ketene acetal failed, a soft enolization, boron-based reaction was highly successful. The second step involves a proposed cascade palladium-catalyzed biscyclization to construct two carbocycles of the natural product. The overall strategy is presented, demonstrating the challenges of the cyclization events in this complex setting.Download high-res image (138KB)Download full-size image

We describe herein the design of a novel molecular scaffold that can induce facile oxidative olefinations when attached to alcohols. Benzylic, homo-, and bishomobenzylic alcohols are utilized. The scaffold can act as a protecting group for the alcohol in other transformations, and it is recoverable in excellent yield. The overall sequence can also be telescoped without purifications of intermediates, representing a net alcohol-based directed ortho-alkenylation.

A variety of substituted indoles and benzofurans are accessed via a platinum catalyzed annulation and vinylogous addition of enol nucleophiles. Several β-dicarbonyl compounds participate in the reaction, as do α-nitro and α-cyano carbonyl species. Subjecting the indole products to acidic conditions results in the formation of fused heterocycles.

The first total synthesis of (±)-gelsenicine is reported. The synthetic route is highly efficient (13 steps), featuring (1) a pivotal metal-catalyzed isomerization/rearrangement process that forges the central core of the molecule and (2) two facile C–N bond-forming steps that establish the flanking heterocycles.

Alkylations of proline-based imidazolidinones are described based on the principle of self-regeneration of stereocenters (SRS), affording high levels of either the cis or trans configured products. Stereoselectivity is dictated solely on the nature of the ‘temporary’ group, where isobutyraldehyde-derived imidazolidinones provide the cis configured products and 1-naphthaldehyde-derived imidazolidinones afford the complementary trans configured products. These stereodivergent products can be readily cleaved to afford both α-alkylated proline enantiomers from readily available l-proline. A series of imidazolidinones were alkylated to investigate the origin of the anti-selectivity. Potential contributions toward the observed anti-selectivity are discussed on the basis of these experiments, suggesting a refined hypothesis for selectivity may be in order.

A full account of our investigation of C–C bond migration in the cycloisomerization of oxygen-tethered 1,6-enynes is described. Under Pt(II) and/or Ir(I) catalysis, cyclic and acylic alkyl groups were found to undergo 1,2-shifts into metal carbenoid intermediates. Interestingly, this process does not appear to be driven by the release of ring strain, and thus provides access to large carbocyclic frameworks. The beneficial effect of CO on the Pt(II) and Ir(I) catalytic systems is also evaluated.

A chromium-catalyzed, visible light-activated net [4 + 2] cycloaddition between dienes and electron-deficient alkenes is described. Gathered evidence, via control experiments, isolated intermediates, and measured redox potentials, points to several converging reaction pathways that afford the cyclohexene adducts, including a photochemical [2 + 2] cycloaddition/vinylcyclobutane rearrangement cascade and a substrate excitation/oxidation sequence to a radical cation intermediate. Notably, the accompanying mechanistic stipulations result in a process that yields regioisomeric compounds from those generated by traditional Diels–Alder cycloadditions.

We describe herein the design of a novel molecular scaffold that can induce facile oxidative olefinations when attached to alcohols. Benzylic, homo-, and bishomobenzylic alcohols are utilized. The scaffold can act as a protecting group for the alcohol in other transformations, and it is recoverable in excellent yield. The overall sequence can also be telescoped without purifications of intermediates, representing a net alcohol-based directed ortho-alkenylation.