Imines axial alkylation

While the steric explanation is consistent with the observed selectivity, it nonetheless presents an incomplete explanation, as alkylation of 2-methyl-4-cyano-l,3-dioxane 17 also proceeded with very high syn-selectivity [11] (Eq. 5). The selective equatorial alkylation can be rationalized as an anfz-anomeric effect that disfavors axial alkylation of the ketene iminate through filled-shell repulsion. Simple lithiated nitriles are known to exist as ketene iminates, but it would be easy to rationalize the preference for equatorial alkylation by considering the relative stability of hypothetical equatorial and axial alkyllithium reagents, vide infra. Preferential equatorial alkylation was also observed by Beau... 

Complexity is added to the study of this system by the ready functionalization of the sulfur atom by alkylation, oxidation and imination. 5-Alkylation to produce a compound such as (9) <76T1873) affords a system in which either of two possible chair conformers possesses an axial t-butyl group, and this system therefore exists preferentially in a twist conformation (10). Where no such conflicts occur the sulfur substituent adopts the equatorial position in a chair form. Inversion of configuration at sulfur in cyclic sulfides has been investigated in the system (11) (12) and the corresponding ylides (13) (14) (77JA2337). 

Stereoselective reduction of cyclohexylimines. Imines of alkyl-substituted cyclohexyl ketones are reduced by this borohydride stereoselectively (>90%) to axial secondary amines. Axial primary cyclohexylamines are prepared conveniently by reduction of the imine derived from/ ,/) -dimethoxybenzhydrylamine and sub.scquent cleavage with formic acid (equation 1). 

In 2007, Maruoka et al. introduced chiral dicarboxylic acids consisting of two carboxylic acid functionalities and an axially chiral binaphthyl moiety. They applied this new class of chiral Brpnsted acid catalyst to the asymmetric alkylation of diazo compounds withA-Boc imines [91]. The preparation of the dicarboxylic acid catalysts bearing aryl groups at the 3,3 -positions of the binaphthyl scaffold follows a synthetic route, which has been developed earlier in the Maruoka laboratory [92]. 

Few alkylations of chiral azaenolates according to the latter reaction sequence are known. An example is alkylation of the conformationally fixed 4-tert-butylcyclohexanone imine which furnished a single product. As evident from the 13C-NMR spectrum the introduced alkyl group is located exclusively in the axial position. The geometry of the C -N double bond is syn, however, after a period of time, the thermodynamically more stable auF-isomer appears. Upon hydrolysis of the imine partial epimerization to the more stable cquatorial-substituted ketone occurs28. 

We think of coenzyme B12 rather in the schematic way shown on the left in Figure 21—cobalt (III) in a tetradentate nitrogen-donor macrocycle with a Co-alkyl bond and a base in axial sites. Much interest resides in the determination of the characteristics of the macrocycles that lead to the stability of the cobalt-carbon bond. The burgeoning supply of new macrocycles presents the opportunity of studying such relationships, and Table XIV provides the first simple correlation of this kind 42, 43), Two ligands from the list gave stable Co-C bonds. One of these, TIM, contains four imines arranged in a-pairs while the other con-... 

The sense of chirality in these hydrosilylations is such that (7 j-(-)-DTBM-SEGPHOS predictably delivers hydride to aryl alkyl ketones fi om the si face to give alcohols of R absolute stereochemistry, which is also true for imines. Stereocontrol at a p-site due to asymmetric 1,4-additions is controlled by either the nature of the geometrical isomer (i.e., or Z) or the axial chirality of the ligand. Thus, by switching from the (/ )- to the (5)-enantiomer of the ligand, or from the E- to the Z-activated olefin isomer, the observed central chirality can be inverted. 

Finally, a direct Mannich-type approach has been developed for the enantioselective synthesis of hydrazines and amines (Scheme 16.40). Thus, by trapping with alkyl diazoacetates some in s/iw-generated acyclic azomethine imines, in the presence of axially chiral dicarboxylic acids, a series of a-diazo-(3-hydrazino esters were obtained with excellent enantioselectivities [86]. 

Acetaldehyde 34, which is the simplest of all enolizable carbonyl compounds but highly reactive as an electrophile, is an inexpensive and versatile two-carbon nucleophile in enamine-based Mannich reactions. Mannich reactions of acetaldehyde as a donor with aryl or alkyl substituted N-Boc-imines 90 are effectively catalyzed by (S) -proline (13) in moderate yield but excellent enantioselectivity (Table 28.6, entries 1 and 2) [47]. Chemical yields are improved up to 87% when N-benzoyl (Bz)-imine is employed in the presence of diaryl prolinol silyl ether 85 with p-nitrobenzoic acid (entry 3) [48]. To suppress side reactions, such as self-aldol reactions, the moderate nucleophilicity of the axially chiral amino sulfonamide 23 is particularly useful for this type of Mannich reaction these conditions give the corresponding adducts 91 in good yield and excellent stereoselectivity (entries 4 and 5) [49]. 

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