Addition to a,-unsaturated Carbonyl Compounds

The Hosomi-Sakurai reaction is a powerful method for conjugate allylation of a,fi-unsaturated ketones [425], In the presence of TiCl4 the allylation occurs smoothly at the y-position of allylsilanes and the / -position of a, -unsaturated ketones. This highly regioselective process has been widely used for introduction of functionalized carbon chains and construction of carbocycles in natural product synthesis [6, 426]. When TBAF is used as catalyst, both conjugate addition and 1,2-addition occur competitively [333]. The fluoride ion-catalyzed procedure is, however, effec- 

---

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... 

Vinylcopper complexes. Use of this highly pure form of CuBr results in improved yields of vinylcopper complexes (1) from 1-alkynes (equation I). The reagents 1 were used in a new synthesis of functionalized trisubstituted alkenes (2) by conjugate addition to a, -unsaturated carbonyl compounds (equjition II). The probable stereochemistry of 2 is shown. The reactions are condueted in a one-flask procedure. ... 

Addition to a, -unsaturated carbonyl compounds is characteristic of organocopper and cuprate compounds, as alkyllithium and Grignard reagents react only with the carbonyl group of enones to give the 1,2-addition products. This synthetically useful reaction has been reviewed by Posner (1972). 

Conjugate Addition to a, -Unsaturated Carbonyl Compounds Other than Ketones. In addition to a, 8-unsaturated ketones, the silylcuprate reagent also reacts with a, 8-unsaturated aldehydes, esters (eq 13), amides, and nitriles, and with vinyl-sulfoxides without needing Lewis acid catalysis as carbon-based cuprates do. With esters, the intermediate enolates, which have the E geometry (20), may be used directly in highly diastereoselective... 

Anhydrous hydrogen chloride, bromide, or iodide will add to alkenes by a carbocationic mechanism to give Markovnikov products. The products may have rearranged structures if the first intermediate carbocation can improve in stability by a 1,2-hydride or alkyl shift. Addition to a, -unsaturated carbonyl compounds affords the -halo compounds (Eq. 6.46) [74], which are prone to elimination and thus often isolated as the acetals. Aqueous... 

Enolate Formation by Conjugate Addition to a, -Unsaturated Carbonyl Compounds 51... 

A number of chiral auxiliaries has been designed for enantioselective 1,4-addition to a, -unsaturated carbonyl compounds. Chiral oxazolidinones are among the most efficient, affording the Michael-adducts with up to 99% ee. Asymmetric conjugate addition of an arylmagnesium reagent to cinnamoyloxazolidinone 151 is the key step in the synthesis of (+)-tolterodine 152, an important muscarinic receptor agonist (Scheme 2-58). 

---