Allylation of Imines and Hydrazones

A good reactivity has been reported for (5)-BINAPO (21.14, 1 equivalent), which promoted the asymmetric allylation and crotylation of the benzoylhydrazone of ethyl glyojqrlate, yielding the corresponding (R)-product in up to 98% ee.  

The best results were achieved with the catalyst system consisting of bis-formamide 21.89 and L-proline (2 equivalents each), giving enantioselec-tivities up to 83%. ° 

90 ( 99 1), whereas the reaction catalysed by (acac)2Ni produced exclusively 21.92 ( 99 1). Substituted analogues of 21.90 and 21.92 have not been reported yet, therefore there is no detail on the diastereoselectivity of these reactions. However, the asymmetric versions employing the parent compounds 21.90 and 21.92 have been investigated. Thus, Nakajima s biquinoline iV iy -dioxide 21.17 (20 mol% loading) afforded 2.91 and 2.93 with modest enantioselectivity ( 62% ee). At the same time, using for-mamide 21.33 (20 mol%) and HMPA (1 equiv), Kobayashi was able to obtain 

91 in up 95% enantiomeric excess with pivalaldehyde as substrate (R = tBu), whereas less-hindered aldehydes exhibited lower enantioselectivity (43-79% ee). Interestingly, benzaldehyde gave racemic 21.91 even when the catalyst loading was increased to 40 mol%. 

96 (10 mol%) also proved efficient for the addition of allenyl tri-chlorosilane (21.92) to acylhydrazone 21.68 that afforded the respective homopropargyl hydrazide 21.94 in 78% ee.  

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Enamines derived from ketones are allylated[79]. The intramolecular asymmetric allylation (chirality transfer) of cyclohexanone via its 5-proline ally ester enamine 120 proceeds to give o-allylcyclohexanone (121) with 98% ee[80,8l]. Low ee was observed in intermolecular allylation. Similarly, the asymmetric allylation of imines and hydrazones of aldehydes and ketones has been carried out[82]. 

In 1997, the first truly catalytic enantioselective Mannich reactions of imines with silicon enolates using a novel zirconium catalyst was reported [9, 10]. To solve the above problems, various metal salts were first screened in achiral reactions of imines with silylated nucleophiles, and then, a chiral Lewis acid based on Zr(IV) was designed. On the other hand, as for the problem of the conformation of the imine-Lewis acid complex, utilization of a bidentate chelation was planned imines prepared from 2-aminophenol were used [(Eq. (1)]. This moiety was readily removed after reactions under oxidative conditions. Imines derived from heterocyclic aldehydes worked well in this reaction, and good to high yields and enantiomeric excesses were attained. As for aliphatic aldehydes, similarly high levels of enantiomeric excesses were also obtained by using the imines prepared from the aldehydes and 2-amino-3-methylphenol. The present Mannich reactions were applied to the synthesis of chiral (3-amino alcohols from a-alkoxy enolates and imines [11], and anti-cc-methyl-p-amino acid derivatives from propionate enolates and imines [12] via diastereo- and enantioselective processes [(Eq. (2)]. Moreover, this catalyst system can be utilized in Mannich reactions using hydrazone derivatives [13] [(Eq. (3)] as well as the aza-Diels-Alder reaction [14-16], Strecker reaction [17-19], allylation of imines [20], etc. 

Although allylation of imines with allylsilanes is encountered less frequently, that with allylstannanes seems more common, probably because of the enhanced nucleo-philicity of the tin reagent compared with the silyl counterpart. Equations (109) [292] and (110) [293,294] illustrate the allylation of imines. In the former reaction, a catalytic amount of the L wis acid, TiCl(OTf)3, is sufficient to bring the reaction to completion. Intramolecular allylation of imines [295] or hydrazones [296] led to the stereoselective construction of amino-cyclic structures, as shown in Eq. (HI) [296]. 

This procedure is applicable to imines and hydrazones as well as carbonyl compounds (Scheme 12.17) [49d]. To expand the utility and apphcabihty of aUylation reactions, more efficient and active Lewis acids have been pursued [50] and the mechanism of allylation in protic solvents has been investigated [51]. 

Allylation of Imines. Al-Benzoyl hydrazones, derived from aromatic and aliphatic aldehydes, undergo allylation with allylSiCH in DMF at 20 °C or in CH2CI2 with excess of DMSO as activator at —78 °C (eq 6). The hydrazones derived from ary-lalkyl ketones have also been reported to react. (V-Aryl aldimines are allylated in DMF at 0 °C. ... 

An unusual temperature dependence on the regioselective behavior of an allylbarium species has been demonstrated in asymmetric allylation with the optically active imine SAMP-hydrazone [SAMP = (A)-(—)-l-amino-2-meth-oxymethylpyrrolidine] (Scheme 10).322 Its reaction with prenylbarium chloride at 0°C produced an a-allylated hydrazine in 60% diastereotopic excess, but at — 78 °C, the y-adduct was generated with 98% diastereotopic excess. The temperature dependence of the ct/y ratio may reflect competition between a kinetically favored y-adduct at low temperature and a thermodynamically preferred ct-form at higher temperatures. 

Organomagnesium compounds react with imines, prepared from 3-methoxy-2-naphth-aldehydes by a 1.4-addition mechanism. This reaction can be performed with high diastere-oselectivity. The method was applied for the synthesis of optically pure S-tetralones . Vinyhnagnesium bromide reacts as an acceptor with a ketone dimethyl hydrazone zincate 207, yielding a 1,1-bimetallic species, which can be reacted sequentially with two different electrophiles (equations 131 and 132) . The reaction proceeds via a metalla-aza-Claisen rearrangement, where the dimethylhydrazone anion behaves as an aza-allylic system . 

Titanium-alkyne complexes Ti(Me3SiC=CC6Hi3)(OR)2, as well as the chiral complex derived from chloro-tris[(—)-menthoxo]titanium/2MgClPr1 and alkynes, react with carbonyl compounds to afford optically active allylic alcohols in up to 38% ee (Scheme 127).184 Introduction of two different electrophiles at each of the acetylenic terminal carbon atoms was possible in a regio- and stereoselective manner.45 Similarly, the titanacyclopentene compounds react with imines, metalloimines, or hydrazones under mild conditions to afford allylic amines or their derivatives in good to excellent yields (Scheme 128).258... 

Imine surrogates. In the Mtinnich reaction and cyanide addition, the use of these hydrazones instead of unstable imines is advantageous. Allylation may also be performed with allyltrichlorosilanes."... 

Most scandium Lewis acids are water-compatible and are often used as Lewis acid catalysts in aqueous media. It was demonstrated that in the presence of 5mol% Sc(OTf)3 acyl hydrazones and imines reacted with tetraallyltin in water-tetrahydorfuran (THF) to give the desired allylated adducts in good yields (Scheme 12.59) [160]. 

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