Allylation of hydrazones

Next to P(0) or N(0) Lewis bases, there are very rare cases where enantiopure sulfoxides are used in combination with silanes. Kobayashi and coworkers reported a highly diastereoselective and enantioselective allylation of hydrazones with chiral sulfoxide 32 (Scheme 23) [76], Massa [77,78] and Bamess [79] reported the asymmetric allylation of aldehydes with enantiopure sulfoxides, respectively, with moderate selectivity. 

A facile and highly selective indium(0)-mediated allylation of hydrazones utilizing BINOL ligands has been described.141 Chiral (7 )-3,3 -bistrifluoromethyl-BINOL has afforded homoallylic amines in up to 97% ee. 

The allylation of hydrazones derived from arylalkyl ketones [42] and of N-aryl aldimines in DMF at 0 °C [46] have also been reported. 

Catalytic Asymmetric Nucleophilic Addition to Achiral Imines 27 Table 1.12 Allylation of hydrazones. 

Allylation of hydrazones derived from aryl alkyl ketones [56] and of N-aryl aldi-mines in DMF at 0°C [61] has also been reported. 

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]. 

Allylation of acyloyl-imidazoles and pyrazoles61 with allyl halide mediated by indium in aqueous media provides a facile regioselective synthesis of P, y-unsaturated ketones (Scheme 11.1), which has been applied to the synthesis of the monoterpene artemesia ketone. The same product can be obtained by indium-mediated allylation of acyl cyanide (Eq. 11.35).62 Samarium, gallium, and bismuth can be used as a mediator for the allylation of nitrones and hydrazones to give homoallylic hydroxylamine and hydrazides in aqueous media in the presence of Bu4NBr (Scheme 11.2).63 The reaction with gallium and bismuth can be increased dramatically under microwave activation. 

Scheme 6.97 Typical products obtained from the 91-catalyzed asymmetric allylation of N-benzoyl-protected aromatic hydrazones. The product configurations were not determined.

Finally, the reaction of hydrazones with ir-allylpalladium complexes may involve insertion of C=N into the allyl ligand.265-266... 

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. 

Homochiral strained allylsilacycles 24 are valuable for uncatalyzed enantioselective allylation of (V-acy I hydrazones derived from aldehydes and ketones (Equation (32)).133,133a The crotylation using 24b and 24c occurs in the same stereospecific manner as observed in the DMF-promoted crotylation using crotyltrichlorosilanes. A cyclic transition state similar to 22 is reasonable also in the allylation using 24. 

The indium-mediated allylation of chiral hydrazones has been investigated. Essentially complete diastereoselectivity and quantitative yields have been realized for substrates derived from both aromatic and aliphatic aldehydes (Scheme 69).270... 

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]. 

The synthon of the a-acrylate anion is available from a secondary a-keto carboxamide by the Shapiro reaction. The secondary a-ketoamide trisylhydrazones ate ptepar in a one-pot synthesis by reaction of the isocyanides with acid chloride, water and trisylhydrazine in sequence. In DME solvent, the hydra-zone (103) is smoothly metallated with BuLi to give Ae trianion (KH). Allylation of the trianion (104) gives the hydrazone (105). Alternatively, warming (104) up to room temperature yields the dianion (106) which can be intercepted with several electrophiles (Scheme 23). The adduct (107) is readily transformed into the rran -iodo lactone (108) stereospecifically (equation 56). This chemistry also has been applied to a new synthesis of -lactams (Scheme 24). ... 

AUylation. Scandium(III) triflate promotes allylation of aldehydes (in the presence of ketone moieties) with allylgermanium reagents in aqueous nitromethane. By adding primary amines as the third component, such reactions deliver homoallylic amines (in such cases the aldehydes react too slowly to cause any chemoselectivity problem) Benzoyl hydrazones react accordingly. ... 

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. 

Scheme 12.86 Intramolecular Pt-catalyzed nucleophilic allylation of aldehydes, oximes, and hydrazones under hydrogenation conditions [7e].

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. ... 

---