Addition to a, 0-unsaturated compounds

Addition to a,/ -Unsaturated Compounds Leading to Bicyclic Products... 

Organozinc reagents have played an important role in the development of efficient catalysts for enantioselective carbon-carbon bond-formation by lj4-addition to a, -unsaturated compounds. Important advantages of the use of organozinc reagents are the option of starting with alkenes (throu hydroboration-zinc transfer procedures) and the tolerance towards functional groups. 

Michael Reaction. 5(47/)-Oxazolones undergo base-catalyzed conjugate addition to activated unsaturated compounds to afford the corresponding C-4 Michael adducts. For example, base-catalyzed addition of a 4-monosubstituted-5(4//)-oxazolone 157 to methyl propiolate yields a mixture of diastereomeric methyl 3-(5-oxo-2-phenyl-2-oxazolin-4-yl)acrylates 158. Hydrolytic ring opening of 158 and subsequent oxidation with lead tetraacetate affords 3-acylacrylates 160... 

Aldol condensation with aldehydes and ketones gives hydroxy compounds (265 — 267) which usually spontaneously lose water (by a reverse Michael addition) to give unsaturated compounds (268). 

Nucleophilic additions of alcohols to a,/ -unsaturated compounds have been performed on alkali metal oxides and hydroxides. Cyanoethylation of various alcohols with acrylonitrile to form 3-alkoxypropanenitriles has been carried out efficiently in the presence of these solid base catalysts at a temperature of 323 k.[68,69] In cyanoethylation of methanol, conversions of 98 % after 2 h in a batch reactor were obtained with MgO, CaO and SrO in contrast, with BaO the conversion was only 68 %. 

We end with a summary of the factors controlling the two modes of addition to a, ( -unsaturated carbonyl compounds, and by noting that conjugate addition will be back again—in Chapters 23 (where we consider electrophilic alkenes conjugated with groups other than C=0) and 29 (where the nucleophiles will be of a different class known as enolates). 

Throughout this review, elimination reactions have been restricted to die loss of an appropriate leaving group from the a-carbon atom, but both -thio and -selenenyl groups can be eliminated with ease from C—OC compounds following oxidation. As a rule, such derivatives are prepared by conjugate addition to a, -unsaturated carbonyl compounds, and therefore formation and elimination constitutes a formal protection of these compounds. 

This chapter includes examples of aliphatic nucleophilic substitution at both sp and sp centers, aromatic nucleophilic substitution, E2 elimination, nucleophilic addition to carbonyl compounds, 1,4-addition to a, -unsaturated carbonyl compounds, and rearrangements promoted by base. 

Mechanistic aspects of copper-catalyzed Grignard addition to a,/ -unsaturated carbonyl compounds have not attracted much attention, probably because of the complex nature of the reagent system [11], but it would resemble that of the 1,4-addition of stoichiometric or higher-order organocopper reagents that have been investigated extensively [15,18,223]. 

But not all photochemical additions to a/ -unsaturated carbonyl compounds take placeatthecarbonyl carbon. Thus the ketone(453)isattackedintheconjugateposition,362... 

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