1,2-addition reactions hydrazones

Hexafluoroacetone azine accepts nucleophiles (ROH, RSH, R NH) in positions 1 and 2 to yield hydrazones [27] Phosphites give open-chain products via a skeletal rearrangement [22] Radical addition reactions are also reported [22] Treatment of tnfluoropyruvates with tosylhydrazine and phosphorus oxychlo-ride-pyndme yields tnfluoromethyl-substituted diazo compounds [24] (equation 3)... 

O-Benzyllactaldehyde dimethylhydrazone 230 allows a substrate control in the addition reaction of organomagnesium halides, leading almost exclusively to the 5yn-isomer 231 (equation 155) . The resulting hydrazide can be reduced on Raney Ni to the corresponding iyw-aminoalcohol 232. The stereoselective Grignard addition to a similar A-formyl hydrazone 233 proceeds with 92% diastereoselectivity (equation 156). The silylation of the amide nitrogen by TMSCl provides the pure iyw-adduct . 

Nakamura and coworkers showed that the addition reaction of zincated hydrazone to vinylmagnesium halide as electrophile gives the s/r1-geminated organodimetal reagent (Scheme 37). The reaction pathway can be considered as a metalla-aza-Claisen-type... 

This reaction was successfully applied to various hydrazones derived from acyclic or cyclic ketones and extended to a variety of unsubstituted vinylsilanes as acceptors (trialkyl, triphenyl and alkoxy vinylsilanes). In all cases, the regioselectivity of the addition reaction was consistent with the formation of a silicon-stabilized organozinc reagent. 

Several reagents for derivatization of carbonyl groups are also available. Dansylhydrazine reacts with carbonyl groups in the presence of trichloroacetic acid, yielding highly fluorescent dansylhydrazones that exhibit, however, limited stability. In addition, fluorescent hydrazones can be produced from carbonyl-containing compounds after their reaction with 4-hydrazino-2-oxa-l,3-diazole or... 

SCHMIDT REACTION. Acid catalyzed addition of hydrazonic acid to carboxylic acids, aldehydes, and ketones to give amines, nitriles, and amides, respectively. 

The reactions of ketone dilithio ,/i-dianions with imines and hydrazones have been investigated.77 The nucleophilic addition reaction to C—N double bonds took place selectively at the -position of dianions to form lithium (Z)-enolates containing a lithium amide portion, which is then transformed into y-amino ketones and related compounds by the subsequent reaction with electrophiles. 

Based on all these considerations, we chose to develop a new type of chiral hydrazone, tailored for use in free radical addition reactions, which would incorporate Lewis acid activation [35-37] and restriction of rotamer populations as key design elements [1-7] (Fig. 2). 

An early transition state is commonly assumed for exothermic radical addition reactions, and this enables approximation of the transition state geometry based on the ground-state structure. From this assumption, we hypothesized that a substituent above or below the plane of the C=N bond in the ground state hydrazone structure... 

Our attention was drawn to photolytic radical generation with hexamethylditin because it showed promise in Kim s prior work with C=N radical acceptors, which included additions of primary radicals [54—60]. Adapting Kim s photolysis conditions, with hexamethylditin in the presence of InCl3, ethyl and isopropyl additions to hydrazone 3a occurred in reasonable yield [48]. Unfortunately, a carbonyl exchange side reaction [46] with acetone (used as a sensitizer under Kim s conditions) interfered with further development of this reaction. 

Although there is ample evidence for nucleophilic additions to benzyne la> and some other unstable angle strained cycloalkyne intermediates 15,27,31,205 207), only a few addition reactions to isolable angle strained cycloalkynes are known which can be classified as nucleophilic. Hydroxylamine and hydrazine add to (31) to yield the corresponding oxime and hydrazone, resp. 208). 

In the classic carbohydrate chemistry addition reactions of carbonyl groups served as valuable tools for sturctural studies of carbohydrates. For example, hydroxyl amine, hydrazine, and phenyl hydrazine react with carbonyl groups to yield oximes and hydrazones. In the presence of an excess... 

There are many examples of acid catalyzed carbonyl addition reactions, such as formation of hydrates (R2C(OH)2), hemiacetals, hemiketals, cyanohydrins, bisulfite compounds, azomethines, oximes, hydrazones, etc. These important reactions are discussed in Vol. 11. 

The postulate that ethylidene is formed in this system rests on an analogy with its presence in the photolysis of diazoethane - and also by analogy with the similarity of the products produced by the photolysis and pyrolysis of other diazirines and by the decomposition of tosyl-hydrazones, which are thought to involve carbene intermediates. Attempts were made to detect ethylidene (by its addition reactions) by photolyzing methyldiazirine in the presence of large excesses of ethylene, propylene, and allene. In no case was any product detected that could be ascribed to the addition of ethylidene to any of these molecules. 

Diastereoselective radical additions to hydrazones have been examined under several reaction conditions. The biphasic reaction of a hydrazone with an isopropyl radical in aqueous NH4C1-CH2C12 (4 1, v/v) proceeded slowly to give the corresponding alkyl-substituted derivative in 73% yield and 95% de after being stirred for 22 h (Scheme 7.18).27 As expected, the diastereoselectivity... 

The Jorgensen group also applied the parent cinchona alkaloids as catalysts to the aza-Michael addition of hydrazones 8 to cyclic enones 9 [4] and the asymmetric deconjugative Michael reaction of alkylidene cyanoacetates 10 with acrolein (11) [5], However, only a moderate level of enantioselectivity was obtained in both reactions (Scheme 9.4). Of note, for the deconjugative Michael reaction, the delocalized allylic anion 12 could be generated via the deprotonation of 10 by the cinchona base and might attack the electrophilic enal at either the a- or the y-position. However, in this study, only the a-adducts were produced. 

A variety of aldehyde hydrazones were screened [24b]. Branching at a saturated a carbon was detrimental in the tin mediated radical additions, but an aromatic benzaldehyde hydrazone 12 offered some success, with yields ranging from 30 to 83% (Table 2.3, entries 5 8). With the exception of 8a, which decomposed under the reaction conditions, the reactions were quite dean. Even in the examples with lower yields, the mass balance after recovery of the hydrazone precursor was generally 80 90%, demonstrating the excellent chemoselectivity of the reactions of radicals with N acylhydrazones. We were delighted to find that the radical additions had occurred with excellent stereocontrol in all secondary and tertiary radical additions to hydrazones 8 and 12 (Table 2.3), with diastereomer ratios ranging from 93 7 to 99 1 [24]. 

The Mn mediated radical additions offer an inherently flexible carbon carbon bond construction approach to amine synthesis. Because of the broad functional group compatibility in both the radical precursor and the aldehyde hydrazone acceptor, the roles of these precursors can be switched to result in the construction of either of two C C bonds at the chiral amine (Scheme 2.10) with excellent stereocontrol. The epimeric configuration can be selected by either (a) employing the enantiomeric auxiliary or (b) interchanging the roles of R and in the alkyl halide and aldehyde precursors [47]. By combining these two tactics, the optimal roles of R and with respect to yield and selectivity can be chosen. Such strategic flexibility contributes to the synthetic potential of these radical addition reactions. 

Under carefully controlled conditions in which the uptake of gas was limited to 2 moles per mole, the products of direct hydroformyla-tion of glycal esters were found to be obtainable. Thus, from di-O-acetyl-D-xylal, 4,5-di-0-acetyl-2,6-anhydro-3-deoxy-D-lyxo- and -xylo-hexose (19 and 20) were isolated in a combined yield of 20% (by way of hydrazone derivatives). Alternatively, these compounds were much more readily prepared by application of the Pfitzner-Moffatt oxidation reaction to the corresponding hydroxymethyl analogs. With tri-O-acetyl-D-glucal, the addition reaction was more suitable for the preparation of the 2,6-anhydroaldose compounds, the yield33 being 70%. 

Addition to imines. Functionalized secondary amines are formed by addition of hydrazones and diazo compounds to aldimines, and these reactions are subject to asymmetric induction by 1. 

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