Functionalized Grignard reagents 1,4-addition

II. PREPARATION OF FUNCTIONALIZED GRIGNARD REAGENTS A. Direct Oxidative Addition of Magnesium to Organic Halides... 

Unfortunately, the preparation of functionalized Grignard reagents via direct oxidative addition of magnesium metal to organic halides still suffers from severe limitations. This is mainly due to the intrinsic high reducing potential of magnesium metal. 

Arylazo tosylates of type 248, which are readily obtained from aniline derivatives 249 in a two-step procedure (equation 162), can be alternatively used as starting materials. This electrophilic nitrogen equivalent 248 reacts with a broad range of functionalized Grignard reagents under mild conditions. Subsequent allylation of the addition products with allyl iodide, followed by reductive cleavage of the resulting hydrazine derivatives... 

Scheme 2-75. Preparation of secondary amines via the addition of functionalized Grignard reagents to aromatic nitro compounds.

Addition of Grignard reagents to ketones and aldehydes was one of the reactions which led to the formulation of Cram s rule. Many ketones and aldehydes have subsequently been examined to determine the degree of stereoselectivity. Cram s rule is obeyed when no special complexing functional groups are present near the reaction site. One series of studies is summarized in Table 8.2. 

Zinc bromide promoted addition of a functionalized benzyl Grignard reagent to the a,/ -unsat-urated y-lactone, 3-(4-methylphenylsulfinyl)-2(5//)-furanone, via a zinc-chelated intermediate, gave, after several synthetic steps, (-)-podorhizon with 95% ee18. 

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