Imines N-acyl

Asymmetric addition to ketimine in a reagent controlled manner has seldom been reported, even by 2008. When we investigated the potential for tbis asymmetric addition around 1992, there were no known examples. In 1990, Tomioka et al., reported the first asymmetric addition of alkyl lithium to N-p-methoxyphenyl aldo-imines in the presence ofa chiral (3-amino ether with 40-64% ee [8] (Scheme 1.11). In 1992, Katritzky reported the asymmetric addition of Et2Zn to in situ prepared N-acyl imine in the presence of a chiral (3-amino alcohol with 21-70% ee [15] (Scheme 1.12). In the same year, Soai et al., reported the asymmetric addition of dialkylzinc to diphenylphosphinoyl imines in the presence of chiral (3-amino alcohols with 85-87% ee [16] (Scheme 1.13). These three reports were, to the best of... 

Gridnev and Terada calculated the optimized structure of the complex derived from phosphoric acid and N-acyl imine [14], wherein the hydrogen-bond complex was observed by density functional theory (DFT) calculations. 

Exploiting the Lewis basic phosphoryl oxygen of Im, Terada reported the direct alkylation of a-diazoesters with N-acyl imines to afford P-amino-a-diazoesters in high yields and ee s (Scheme 5.12) [23]. Earlier, Johnston had observed that catalytic TfOH promoted aziridine formation (Aza-Darzens reaction) between diazoacetates and N-benzyl imines [24]. The authors propose that aziridine formation is circumvented through C—H bond cleavage by the phosphoryl oxygen of 1 (Intermediate A). However, as noted by the authors, the low nucleophilicity of N-acyl imines might also be considered as the cause of this selective transformation. 

H,6H-l,3,5-Dioxazin 6,6-Bis-[trifluormethyl]-4-tert.-butyl-2-trichlormethyl- El4b. 280 (N-Acyl —imin + Chloral)... 

H,6H-l,3,5-Oxatbiazin 2,6,6-Tris-[trifluormethyl]-4-(4-chlor-phenyl)- El4b, 281 (N-Acyl-imin + F3C—CN)... 

Ci2HsC14F6NOS 2H,6H-l,3,S-Oxathiazin 6,6-Bis-[trifluormethyl]-4-(4-chlorphe-nyl)-2-trichlormethyl- E14b, 280 f. (N-Acyl-imin I Chloral bzw. C13C-CN)... 

Bis-[trifluormethyl]-4-phenyl-6-trichlormethyl- E14a/2, 354/754 (R-CS-NH2/R-CHO + Keton) E14b, 281 (N-Acyl-imin + CI3C-CN)... 

H,6H-l,3,5-Dioxazin 4-(4-Chlor-phenyl)-2,2,6,6-tetrakis-[trifluor-methyl]- E14b, 279 (N —Acyl —imin + Keton)... 

Weinreb, S. M., Scola, P. M. N-acyl imines and related hetero dienes in [4+2]-cycloaddition reactions. Chem. Rev. 1989, 89,1525-1534. Marcelis, A. T. M., van der Plas, H. C. Diels-Alder reactions of diazines and pyridines. Trends Heterocycl. Chem. 1990, 1,111-123. 

Matsuoka, T., Harano, K., Uemura, T., Hisano, T. Hetero Diels-Alder reaction of N-acyl imines. I. The reaction of N -thiobenzoyl-N,N-dimethylformamidine with electron-deficient dienophiles. Stereochemical and mechanistic aspects. Chem. Pharm. Bull. 1993, 41, 50-54. Mikami, K., Motoyama, Y., Terada, M. Asymmetric Catalysis of Diels-Alder Cycloadditions by an MS-Free Binaphthol-Titanium Complex Dramatic Effect of MS, Linear vs Positive Nonlinear Relationship, and Synthetic Applications. J. Am. Chem. Soc. 1994, 116, 2812-2820. 

Scheme 1.8 Preparation of N acyl imines from nonenolizable aldehydes.

Figure 1.8 Transition state models for the crotylation of N acyl imines.

Since the initial report in 1962 by Moten and Muller of the cycloaddition of an A(-acyl imine with a conjugated diene,a number of examples of this type of reaction have appeared. In general, A(-acyl imines are highly reactive, unstable species which are rarely isolated, but rather are generated in situ from stable precursors. Depending upon the method of formation of the particular dienophile and the reaction conditions, a neutral N-acyl imine or a protonated (or Lewis acid complexed) N-acyl immonium ion may be involved in the Diels-Alder reaction. 

Grieco has used his aqueous iiiunonium Diels-Alder procedure to effect a number of intramolecular reactions. In one case, diene aldehyde (83) was treated with ammonium chloride to afford a 2.2 1 mixture of isomeric Diels-Alder adducts (87) and (85) (Scheme 10). Since intermediate immonium ions (84)/(86) cannot participate in secondary orbital effects as is the case with N-acyl imines (cf. 80), these results are probably due to steric factors. It was suggested that adduct (85) derives from conformation (84) and adduct (87) comes from (86). Conformer (84) is favored since there is a severe eclipsing of Ha/Hb in (86). A more detailed account of the stereochemical aspects of intramolecular Diels-Alder reactions can be found in Chapter 4.4. 

Although the literature abounds with examples of aromatic amidoalkylations with N-acyl imines [la, 56], virtually nothing has been done in this area with N-sulfonyl imines. An amidoalkylation of this type involves reaction of a-methoxy sulfonamide 170 with anisole to afford alkylation products 171 and 172 [Eq. (33)] [25c]. In a heteroaromatic version of this process, thiophene was... 

Weinreb et al. have systematically explored the intramolecular Diels-Alder reaction of N-acyl-imines generated from the bisamides (79) to extend the usefulness of this little studied reaction. 

Even the very efficient enantioselective catalysts used in organozinc addition reactions to carbonyl compounds failed to catalyze the corresponding addition reactions to nonactivated imines such as N-silyl-, N-phenyl-, or A-benzyl-imines. However, enantioselective additions of dialkylzinc compounds to more activated imines, like A7-acyl- or N-phosphinoyl-imines, in the presence of catalytic or stoichiometric amounts of chiral see Chiral) aminoalcohols, have been recently reported. For example, in presence of 1 equiv of (N,N-dibutylnorephedrine) (DBNE) diethylzinc reacts with masked N-acyl imines like A7-(amidobenzyl)benzotriazoles, to give chiral N- -phenylpropyl) amides with up to 76% e.e. (equation 68). 

Amides from N-Acyl Imines and Related Heterodienes in [4+2]-Cycloaddition Reactions"... 

N-acyl imines [144]. A slightly modified chiral Br0nsted acid 185 was found to catalytically induce addition of indoles to N-Boc-protected enecarbamates ISK) in high yields and enantioselectivities (Scheme 8.51) [145]. In a related study, Zhou demonstrated the use of a-aryl enamides to obtain optically enriched tertiary amine products [146]. 

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