Rick Danheiser

Cyclohexenol annulation via the alkoxy-accelerated rearrangement of vinylcyclobutanes

Abstract The lithium and potassium salts of 2-vinylcyclobutanols undergo vinylcyclobutane rearrangement at 25–70°, providing an efficient method for the synthesis of 3-cyclohexenol derivatives. 2-Vinylcyclobutanones are prepared from α,β-unsaturated carbonyl compounds by the method of Trost and via [2 + 2]-cycloadditions of olefins and vinylketenes. Addition of hydride or alkyllithium reagents then generates 2-vinylcyclobutanol salts which directly rearrange to afford 3-cyclohexenols. The two methods constitute new [3 + 3]- and [4 + 2]-annulation approaches to 6-membered carbocycles.

The reaction of allenylsilanes with α,β-unsaturated acylsilanes: new annulation approaches to five and six-membered carbocyclic compounds

Abstract The reaction of α,β-unsaturated acylsilanes with allenylsilanes can be directed to produce either five or six-membered carbocyclic compounds.

Cyano Diels-Alder and cyano ene reactions. Applications in a formal [2 + 2 + 2] cycloaddition strategy for the synthesis of pyridines.

Two metal-free, formal [2 + 2 + 2] cycloaddition strategies for the construction of polycyclic pyridine derivatives are described that proceed via pericyclic cascade mechanisms featuring the participation of unactivated cyano groups as enophile and dienophile cycloaddition partners.

Formal [2+2+2] Cycloaddition Strategy Based on an Intramolecular Propargylic Ene Reaction/Diels-Alder Cycloaddition Cascade

A formal, metal-free, [2 + 2 + 2] cycloaddition strategy is described based on a cascade of two pericyclic processes. The first step involves an intramolecular propargylic ene reaction of a 1,6-diyne to generate a vinylallene, which then reacts in an inter- or intramolecular Diels-Alder reaction with an alkenyl or alkynyl dienophile. Reactions involving unsymmetrical alkenyl and alkynyl dienophiles proceed with good to excellent regioselectivity, and the diastereoselectivity in the Diels-Alder step is also high, with endo cycloadducts produced as the exclusive products of the reaction. In the case of alkynyl dienophiles, [4 + 2] cycloaddition initially generates an isotoluene-type intermediate that isomerizes to the isolated aromatic product upon exposure to a catalytic amount of DBU at room temperature. The mechanism of several earlier fully intramolecular related transformations have been shown to involve an analogous process rather than the diradical-mediated pathways proposed previously.

Trialkylsilyloxyalkynes: Synthesis and aromatic annulation reactions

Substituted resorcinols are produced by the thermal addition of cyclobutenones to trialkylsilyloxyalkynes. The dehydrobromination of (Z)-2-bromovinyl silyl ethers has been employed in the first synthesis of trialkylsilyloxyethyne derivatives.

Chemistry of cyclopropylacylsilanes I. α-functionalized acylsilane reagents for the cyclopropanation of electrophilic alkenes

Abstract Two classes of α-functionalized acylsilane reagents have been developed to effect the cyclopropanation of electrophilic alkenes. The lithium enolate derivatives of the α-haloacylsilanes 14,15, and 17 react with a wide variety of electron-deficient olefins to afford cyclopropylacylsilanes in good yield. In the case of cyclopropanations of α,β-unsaturated carbonyl compounds using the α-chloro reagent 14, the predominant stereoisomers produced are generally the cyclopropanes in which the acylsilane moiety has a cis stereochemical relationship to the carbonyl group. The synthesis and chemistry of the acylsilane sulfur ylide derivative 33 is also described. This compound has proved particularly useful as a reagent for the cyclopropanation of α,β-unsaturated aldehydes. Efficient syntheses of 33 as well as the α-haloacylsilanes 14, 15, and 17 (in 2–4 steps from commercially available starting materials) are also reported.

Conjugate addition of allylsilanes to α,β-unsaturated acylsilanes

Abstract α,β-Unsaturated acylsilanes serve as highly reactive carboxylic acid equivalents in conjugate allylation reactions with allylsilane derivatives.

Total synthesis of Dan Shen diterpenoid quinones

Abstract A photochemical aromatic annulation strategy provides efficient synthetic routes to the diterpenoid quinones (+)-danshexinkun A, danshexinkun B, danshexinkun C, (−)-dihydrotanshinone I, and tanshinone I.

A general method for the reductive dechlorination of 4,4-dichlorocyclobutenones

Abstract Exposure of 4,4-dichlorocyclobutenones to the action of zinc dust in ethanol containing 5 equiv each of AcOH and TMEDA results in smooth reductive dechlorination producing simple cyclobutenones.

Synthesis of Amides and Lactams in Supercritical Carbon Dioxide

Supercritical carbon dioxide can be employed as an environmentally friendly alternative to conventional organic solvents for the synthesis of a variety of carboxylic amides. The addition of amines to ketenes generated in situ via the retro-ene reaction of alkynyl ethers provides amides in good yield, in many cases with ethylene or isobutylene as the only byproducts of the reaction. Reactions with ethoxy alkynes are performed at 120-130 degrees C, whereas tert-butoxy derivatives undergo the retro-ene reaction at 90 degrees C. With the exception of primary, unbranched amines, potential side reactions involving addition of the amines to carbon dioxide are not competitive with the desired C-N bond-forming reaction. The amide synthesis is applicable to the preparation of beta-hydroxy and beta-amino amide derivatives, as well as amides bearing isolated carbon-carbon double bonds. Preliminary experiments aimed at developing an intramolecular variant of this process to afford macrolactams suggest that the application of CO(2)/co-solvent mixtures may offer advantages for the synthesis of large-ring compounds.