Tetrasubstituted olefins through the stereoselective catalytic intermolecular conjugate addition of simple alkenes to α,β-unsaturated carbonyl compounds.
Tetrasubstituted olefins through the stereoselective catalytic intermolecular conjugate addition of simple alkenes to α,β-unsaturated carbonyl compounds.
Project description:A new method for the stereoselective synthesis of tetrasubstituted olefins is described. β-Ketophosphonates are alkylated via conventional methods, and a Grignard reagent is used to diastereoselectively add to the carbonyl group of the resulting intermediates. The elimination of hydroxyl phosphonates yielded the desired tetrasubstituted olefins in a stereoselective manner. Thus, homofarnesenes of fire ant trail pheromones have been synthesized efficiently using this strategy.
Project description:A highly stereocontrolled synthesis of tetrasubstituted acyclic all-carbon olefins has been developed via a stereoselective enolization and tosylate formation, followed by a palladium-catalyzed Suzuki-Miyaura cross-coupling of the tosylates and pinacol boronic esters in the presence of a Pd(OAc)2/RuPhos catalytic system. Both the enol tosylation and Suzuki-Miyaura coupling reactions tolerate an array of electronically and sterically diverse substituents and generate high yield and stereoselectivity of the olefin products. Judicious choice of substrate and coupling partner provides access to either the E- or Z-olefin with excellent yield and stereochemical fidelity. Olefin isomerization was observed during the Suzuki-Miyaura coupling. However, under the optimized cross-coupling reaction conditions, the isomerization was suppressed to <5% in most cases. Mechanistic probes indicate that the olefin isomerization occurs via an intermediate, possibly a zwitterionic palladium carbenoid species.
Project description:We have designed a new sequential carbocupration and sulfur-lithium exchange that leads stereo- and regioselectively to trisubstituted alkenyllithiums. Subsequent trapping with various electrophiles yields tetrasubstituted olefins with good control of the double-bond geometry (E/Z ratio up to 99:1). The novel sulfur-lithium exchange could be extended to the stereoselective preparation of Z-styryl lithium derivatives with almost complete retention of the double-bond geometry.
Project description:A copper-catalyzed conjugate addition of alkylboron compounds (alkyl-9-BBN, prepared by hydroboration of alkenes with 9-BBN-H) to alkynoates to form ?-disubstituted acrylates is reported. The addition occurred in a formal syn-hydroalkylation mode. The syn stereoselectivity was excellent regardless of the substrate structure. A variety of functional groups were compatible with the conjugate addition.
Project description:Two-component Giese type radical additions are highly practical and established reactions. Herein, three-component radical conjugate additions of unactivated alkenes to Michael acceptors are reported. Amidyl radicals, oxidatively generated from ?-amido oxy acids using redox catalysis, act as the third reaction component which add to the unactivated alkenes. The adduct radicals engage in Giese type additions to Michael acceptors to provide, after reduction, the three-component products in an overall alkene carboamination reaction. Transformations which can be conducted under practical mild conditions feature high functional group tolerance and broad substrate scope.
Project description:In this communication, we describe an unprecedented highly enantioselective catalytic conjugate addition of simple alkyl thiols to alpha,beta-unsaturated N-acylated oxazolidin-2-ones catalyzed by acid-base bifunctional catalysis. This reaction provides a useful catalytic method for the synthesis of optically active chiral sulfur compounds that are otherwise difficult to prepare by asymmetric catalysis. The successful development of this reaction resulted from a discovery that, upon proper modification, a cinchona alkaloid bearing a thiourea functionality at 6' position can afford highly efficient catalysis for asymmetric conjugate additions.
Project description:A catalytic 1,2-oxyhalogenation method that converts non-conjugated internal alkynes into tetrasubstituted alkenes with high regio- and stereoselectivity is described. Mechanistically, the reaction involves a PdII /PdIV catalytic cycle that begins with a directed oxypalladation step. The origin of regioselectivity is the preference for formation of a six-membered palladacycle intermediate, which is facilitated by an N,N-bidentate 2-(pyridin-2-yl)isopropyl (PIP) amide directing group. Selectivity for C(alkenyl)-X versus -N (X=halide) reductive elimination from the PdIV center depends on the identity of the halide anion; bromide and iodide engage in C(alkenyl)-X formation, while intramolecular C(alkenyl)-N reductive elimination occurs with chloride to furnish a lactam product. DFT calculations shed light on the origins of this phenomenon.
Project description:The Pd-catalyzed addition of organozinc reagents to unsaturated carbonyls in the presence of carbon monoxide provides 1,4-diketones in good yield. The reaction was studied with a number of substituted cyclic and acyclic ketones as well as alpha,beta-unsaturated aldehydes.
Project description:Atom transfer radical addition of haloalkanes and α-halocarbonyls to olefins is efficiently performed with the photocatalyst Ir[(dF(CF(3))ppy)(2)(dtbbpy)]PF(6). This protocol is characterized by excellent yields, mild conditions, low catalyst loading, and broad scope. In addition, the atom transfer protocol can be used to quickly and efficiently introduce vinyl trifluoromethyl groups to olefins and access 1,1-cyclopropane diesters.