Tetrasubstituted Olefins through the Stereoselective Catalytic Intermolecular Conjugate Addition of Simple Alkenes to α,β‐Unsaturated Carbonyl Compounds

Abstract

Recent efforts in designing expeditious catalytic synthesis of tetrasubstituted olefins have in part been stimulated by growing needs for developing generally applicable methods for tamoxifen analogs (anti-breast cancer drug) as well as for photo-responsive organic materials and molecular devices.[1] A number of different catalytic methods have been developed to synthesize tetrasubstituted olefins, including: Suzuki-type Pd-catalyzed coupling reactions,[2] Ni- and Rh-catalyzed exocyclization methods,[3] Ni- and Pd-catalyzed nucleophilic coupling reactions of alkynes[4] and of alkyne-to-arylboronic acids,[5] Ti-catalyzed tandem alkyne-epoxide-ethyl acetate coupling,[6] and the ring-closing olefin metathesis by using Grubbs catalyst.[7] Though catalytic conjugate addition of alkenes has been recognized as a potentially powerful synthetic methodology in forming tetrasubstituted olefins, generally applicable conjugate addition of simple olefins to α,β-unsaturated carbonyl compounds has been hampered by lack of reactivity of the olefin substrates and due to the formation of homocoupling and other byproducts. Chelate-assisted C–H insertion[8] and cross coupling methods[9] are among the most notable advances in catalytic coupling reaction of enones with simple alkenes. Ni-catalyzed conjugate addition and allylic substitution reactions of simple alkenes have also been reported recently.[10] We recently discovered that the cationic complex [(C6H6)(CO)(PCy3)RuH]+BF4− (1) is a highly effective catalyst precursor for the coupling reactions of arylketones and alkenes involving C–H activation.[11] Herein we report a novel catalytic synthesis of tetrasubstituted olefins from the intermolecular conjugate addition reaction of simple olefins to α,β-unsaturated carbonyl compounds.

Direct Intramolecular Conjugate Addition of Simple Alkenes to α,β-Unsaturated Carbonyls Catalyzed by Cu(OTf)2

“…In 2008, Jamison and Ogoshi independently reported the addition of an unactivated alkene to enones under the catalysis of Ni(0). Yi has advanced ruthenium catalysts , for this reaction to synthesize tetrasubstituted olefins. In an early work, Snider and co-workers reported that a stoichiometric amount of a Lewis acid catalyzed the addition of alkenes to α,β-enones .…”

“…As a continuation to our recent efforts on carbocation based functionalization of olefins, we have explored the direct intramolecular addition of alkenes to enones. In this regard, a simple Lewis acids such as Cu(OTf) 2 was found to be a viable catalyst for the intramolecular alkene addition, providing a facile route for the synthesis of six- and five-membered carbocycles ,, (Scheme ).…”

Scope and Mechanistic Study of the Coupling Reaction of α,β-Unsaturated Carbonyl Compounds with Alkenes: Uncovering Electronic Effects on Alkene Insertion vs Oxidative Coupling Pathways

“…Previously, we also observed similar results from the coupling reaction of ( E )-C 6 H 5 CH=CHCO 2 Et with propene in forming the insertion product 2 . 23 It should be mentioned that the coupling reaction of ( E )-C 6 H 5 CH=C(CH 3 )CONHCH 3 with an electron-deficient alkene such as 4-chlorostyrene led to a mixture of linear and branched insertion products 3p and 3q and the oxidative coupling product 4f ((3p + 3q):4f = 85 : 15), and we observed the noticeable carbon isotope effect only from the insertion products 3p and 3q .…”

“…Previously, we have successfully trapped and isolated the catalytically relevant ruthenium-allyl species 9 , which provides another supporting evidence for the Ru-alkene-hydride complex 10 . 23 …”

Tetrasubstituted Olefinic Xanthene Dyes: Synthesis via Pd-Catalyzed 6-exo-dig Cyclization/C–H Activation of 2-Bromobenzyl-N-propargylamines and Solid State Fluorescence Properties

“…Conjugated tetrasubstituted olefins have attracted much attention from organic chemists due to their application in photoresponsive organic materials, molecular devices, and also in the field of biology . A number of different methods have been developed to synthesize tetrasubstituted olefins, including the McMurry reaction, Wittig reaction, and transition metal catalyzed coupling reactions . Recent approaches toward the synthesis of tetrasubstituted olefins involve palladium catalyzed intramolecular carbopalladation of an in situ formed oxidative addition adduct (Ar–Pd–X) to the internal alkyne followed by cross-coupling with a organocopper or organostannane or by direct C– H activation (Scheme ).…”