Grignard, addition, aldehyde conjugate

Corey chose a Wittig-style (HWE) reaction to control the aldol process and copper-catalysed addition of vinyl Grignard for the conjugate addition. Oxidation with NaI04 and catalytic OSO4 gave the keto-aldehyde 35 which cyclised cleanly under equilibrating conditions. 

In the case of a Grignard reagent reacting as the nucleophile, the amounts of normal addition and conjugate addition depend on the steric hindrance at the carbonyl carbon and the /3-carbon. Reaction with an a,/3-unsaturated aldehyde usually results in the formation of the product from attack at the unhindered aldehyde carbon (1,2-addition), as shown in the following equation ... 

Conjugate addition of an alkyl group to an c /S-unsaturated ketone (but not aldehyde) is one of the more useful 1,4-addition reactions, just as direct addition of a Grignard reagent is one of the more useful 1,2-additions. 

If thioamide enolates are prepared by conjugate addition of Grignard reagents to a,/3-unsaturated thioamides of secondary amines, the reaction of these enolates with aldehydes affords anti aldols. These results are rationalized by the formation of a boat-like, chelate transition state" Representative examples are provided in equation 112 and Table 16. 

In place of a Grignard reagent, several homoenolate equivalents have also been employed. Kempt 1 7 reported the titanium-mediated addition of /V-alkylmethylacrylamide dianions to N-protected a-amino aldehydes (Scheme 8). Pyrolytic cyclization affords a 3-methylenetetrahydrofuran-2-one and the side chain of C3 is appended via conjugate addition. The resulting lactone can be converted into the 1-hydroxyethylene dipeptide by hydrolysis. The stereochemistry of the C6 atom is the same as that of the a-amino aldehyde. However, the stereoselectivities of the reactions regarding the C3 and C5 atoms are unsatisfactory. 

Conjugate addition to nitroarenes.4 Grignard reagents undergo facile conjugate addition to nitrobenzene (equation I). In fact only aldehydes can compete successfully with nitroarenes in this reaction. 

Acetoacetic Ester Synthesis Section 20.4 Addition of an Alcohol to an Aldehyde or a Ketone Section 18.9 Figure 18.5 Addition of a Carbene to an Alkene Section 11.8 Addition to a Conjugated Diene Section 11.13 Addition of a Grignard Reagent to an Aldehyde or a Ketone Section 18.6... 

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