Hydrazones with organometallic

Additions of organometallics to the C=N bond of imines, oximes, hydrazones, and nitrones have been reviewed, with emphasis on the issues of reactivity and selectivity. Recent advances in enantioselective addition to imines of ketones are highlighted. 

Imines with an adjacent chiral auxiliary undergo diastereoselective addition of organometallic reagents in a similar fashion, as discussed above (equation 122)487. The products are readily converted into enantiomeric /J-amino alcohols, which are useful in further synthetic sequences or the target moiety in some natural products. Other such syntheses have been performed via additions to both imines488-490 and the related hydrazone moiety491-493. 

The transition metal catalyzed synthesis of arylamines by the reaction of aryl halides or tri-flates with primary or secondary amines has become a valuable synthetic tool for many applications. This process forms monoalkyl or dialkyl anilines, mixed diarylamines or mixed triarylamines, as well as N-arylimines, carbamates, hydrazones, amides, and tosylamides. The mechanism of the process involves several new organometallic reactions. For example, the C-N bond is formed by reductive elimination of amine, and the metal amido complexes that undergo reductive elimination are formed in the catalytic cycle in some cases by N-H activation. Side products are formed by / -hydrogen elimination from amides, examples of which have recently been observed directly. An overview that covers the development of synthetic methods to form arylamines by this palladium-catalyzed chemistry is presented. In addition to the synthetic information, a description of the pertinent mechanistic data on the overall catalytic cycle, on each elementary reaction that comprises the catalytic cycle, and on competing side reactions is presented. The review covers manuscripts that appeared in press before June 1, 2001. This chapter is based on a review covering the literature up to September 1, 1999. However, roughly one-hundred papers on this topic have appeared since that time, requiring an updated review. 

Carbanions derived from organometallic reagents react with aryldiazoalkanes diazoketones and diazoesters to yield hydrazones after hydrolysis (7). 

Organometallic addition to the /V-methoxy-A -methylamide (15) also affords an exceptionally stable tetrahedral intermediate (16) and carbonyl-protecting group, first used in the synthesis of X-206. Deprotonation of the hydrazone in intermediate (16) was subsequently carried out with lithium diisopropylamide. The resulting dianion initiated a novel attack upon epoxide (17) and in the ensuing transformation was followed by tetrahydrofuran ring formation as depicted, in 71% yield, all in one pot (Scheme 4). 

Hydrazine linker on Merrifield resin was reacted with various aldehydes, affording the corresponding hydrazones. 1,2-Addition of various organometallics to the supported hydrazones was investigated. 

The addition of a variety of organometallic reagents to imines and hydrazones (74) of 2-acyl-1,3-oxathianes derived from pulegone proceeds with very high diastereoselectivity (Equation (39)), the addition of lanthanide salts reversing the sense of asymmetric induction <90JA8189,94CL831). 

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