Grignard reagents, bonding conjugate addition

In an a,P-unsaturated carbonyl system, the addition could be either 1,2 or 1,4, i.e. simple or conjugate. With Grignard reagents, the nucleophilic addition can be either 1,2 or 1,4, and often depends upon any steric factors that are present in the substrate. When an a,P-unsaturated carbonyl compound is treated with a carbanion, particularly one that is stabilised by a carbonyl group, the resultant 1,4-addition with the formation of a new carbon/carbon bond is called the Michael reaction. If the reaction occurs intramolecularly, it is called the Robinson annulation reaction. 

Conjugate addition of vinyllithium or a vinyl Grignard reagent to enones and subsequent oxidation afford the 1.4-diketone 16[25]. 4-Oxopentanals are synthesized from allylic alcohols by [3,3]sigmatropic rearrangement of their vinyl ethers and subsequent oxidation of the terminal double bond. Dihydrojasmone (18) was synthesized from allyl 2-octenyl ether (17) based on Claisen rearrangement and oxidation[25] (page 26). 

Substantially high diastereoselectivity was accomplished by the conjugate addition of Grignard reagents to the amide 1 derived from 1-ephedrine32. The reagent attacked from the Re-face of the double bond, as shown in 2, via a chelated intermediate. Low asymmetric induction was observed when butyllithium was used instead of butylmagnesium bromide. 

Nucleophilic addition to C=0 (contd.) ammonia derivs., 219 base catalysis, 204, 207, 212, 216, 226 benzoin condensation, 231 bisulphite anion, 207, 213 Cannizzaro reaction, 216 carbanions, 221-234 Claisen ester condensation, 229 Claisen-Schmidt reaction, 226 conjugate, 200, 213 cyanide ion, 212 Dieckmann reaction, 230 electronic effects in, 205, 208, 226 electrons, 217 Grignard reagents, 221, 235 halide ion, 214 hydration, 207 hydride ion, 214 hydrogen bonding in, 204, 209 in carboxylic derivs., 236-244 intermediates in, 50, 219 intramolecular, 217, 232 irreversible, 215, 222 Knoevenagel reaction, 228 Lewis acids in, 204, 222 Meerwein-Ponndorf reaction, 215 MejSiCN, 213 nitroalkanes, 226 Perkin reaction, 227 pH and, 204, 208, 219 protection, 211... 

The conjugate addition of organometallic reagents to an electron-deficient carbon-carbon double bond is one of the most widely used synthetic methods to generate enolate. It is well known that Grignard reagents usually give a mixture of 1,2- and 1,4-addition... 

L. Miginiac, Nucleophilic Additions to Conjugated Carbon-Heteroatom Multiple Bonds O, S, N, in Handbook of Grignard Reagents (G. S. Silverman, P. E. Rakita, Eds.), Marcel Dekker Inc., New York, 1996, 391-396... 

The 5-arylidene derivatives (e.g.,96) react with Grignard reagents via 1,4-conjugate addition to the exocyclic double bond to afford 97 [Eq. (28)] heterocyclic ring opening does not occur under these conditions.121 126,134,138 Other nucleophiles, such as p-thiocresol and piperidine, add 1,4 to exocyclic double bonds to give the simple adducts 97 (R = SAr and NR 2, respectively). 134 5-Methyl-3-phenyl-2-phenylimino-4-thiazolidinone undergoes... 

---