Nickel-catalyzed conjugate addition of organoaluminum acetylides to .alpha.,.beta.-enones

Abstract

Nickel-Catalyzed Conjugate Addition of Organoaluminum Acetylides to @EnonesSir:Conjugate addition of organometallic compounds to a,@unsaturated ketones is a widely employed reaction in organic synthesis. Organocuprates are commonly employed for 1,4 addition of alkyl and alkenyl groups to a,@-unsaturated ketones;' however, cuprates cannot be used in alkynylation reactions owing presumedly to the strength of the alkynylcopper( I) ligand bond.2 Several sequences have been reported, however, which do achieve conjugate addition of alkynyl units, but each suffers severe limitations. Both acetylenic alanes3 and boranes4 conjugately add to a,@-enones but only to those capable of achieving an s-cis conformation. Of the methods reported which can be applied to fixed S-trans enones (such as 2-cyclohexenone), requires a convenient hydroxyl functional group for direction of intramolecular attack by an alane; the other5 is indirect and involves addition of di(tri-n-butylstanny1)ethylene by cuprate addition and subsequent oxidative elimination of a stannyl group to give, overall, conjugate addition of acetylide to the enone. Extension to alkyl acetylides by this latter method has not been reported. We recently noted6 that a catalyst prepared from Ni(acac)2 and diisobutylaluminum hydride (1 :1) would catalyze the conjugate addition of (a1kenyl)zirconium complexes to a,@-enones. We wish to report herein that this catalyst will, as well, catalyze conjugate addition of terminal alkynyl units to a,@-unsaturated ketones. This procedure is the first one, to the best of our knowledge, which enables this addition to ordinary S-trans enones.A typical procedure for effecting conjugate addition by this route is illustrated as follows.To Ni(acac)2 in ether at 0 O C is added Dibah in toluene solution. The reaction mixture rapidly turns dark red-brown. To this red-brown solution is then added a dialkylaluminum acetylide (prepared in the usual manner from the lithium acetylide and dialkylaluminum chloride)' as a solution in ether. The reaction mixture is cooled to -5 "C and the unsaturated ketone in ethereal solution is added dropwise over a period of 15 min. The reaction mixture is allowed to stir at -5 OC for several hours. Hydrolysis at 0 OC with saturated KH2P04 (aqueous) solution is then followed by addition of just enough of 10% H2S04 (aqueous) to dissolve aluminum salts. The organic layer is washed with saturated N a H C 0 3 and NaCl solutions and is then dried. Removal of solvent and separation of products on silica gel gives the conjugate adduct.

Synthesis and Reactivity of Mixed Dimethylalkynylaluminum Reagents

“…Indeed, the selective 1,4-addition of alkynyl groups to ,-unsaturated compounds can be observed in the presence of nickel catalysts (Scheme 24). 48 In this case, an excess of the dimethylaluminum reagent was necessary to prevent undesired side reaction of the final aluminum enolate with the unreacted enone.…”

Alkynyl- and allenyl-silanes

“…The ethynyl unit can be induced to add to s-frarts-orye-unsaturated ketones in the manner shown 21 in Scheme 13.5: previous methods were either multi- step, or succeeded only with s-cis enones, i.e., when a cyclic transition state was possible. The ethynyl vinyl thioether (7) is readily obtained 22 from ethynyl trimethylsilane (Scheme 13.6).…”

Alkynylaluminum Synthesis Catalyzed by a Zwitterionic Neodymium(III) Heterobimetallic Compound

“…Organoaluminum alkynyl transfer agents are useful in conjugate additions to α,β-unsaturated ketones, , alkynylation of carbonyls, , and ring opening of epoxides, lactones, and aziridines . These reagents are typically synthesized by the salt elimination of corresponding lithium acetylides and dialkylaluminum chlorides and used in situ (Scheme a). , Routes avoiding salt formation and separation are potentially advantageous; however, the uncatalyzed reactions of terminal alkynes and trialkylaluminums provide mixtures of alkynyl- and vinylaluminums from protonolytic alkane elimination and carboalumination, respectively (Scheme b). − The ratio of products varies with the substituents on both aluminum and terminal alkyne starting materials.…”