N benzoyl imines

Antilla and coworkers further extended their methodology to the addition of an oxygen nucleophile, instead of a nitrogen nucleophile (see Scheme 3.54), to imines (Scheme 3.56) [115]. They successfully developed the catalytic enantioselective addition reaction of alcohols as oxygen nucleophiles with N benzoyl imines using chiral phosphoric acid Ig. The method provides straightforward access to chiral hemiaminal ethers with high enantioselectivities. 

At the same time, Antilla et al. developed a vaulted biphenanthrol (VAPOL)-based magnesium phosphate 20b mediated asymmetric aza-Darzens reaction for the synthesis of chiral aziridine derivatives. The catalyst was prepared in an identical procedure to the previously described process with VAPOL-derived phosphate and magnesium fert-butoxide, and applied in the enantioselective aza-Darzens reaction of N-benzoyl imines 23 and ot-chloro-1,3-diketone 24. The process formed a series of substituted aziridines 25 bearing various substituents at the aromatic ring, with good... 

Furthermore, the asymmetric catalysis of 27 could accommodate vinylogous aza-enamines as a source of an alkenyl unit, and the use of 27d bearing the 2,6-dimethyl-4-(l-adamantyl)phenyl groups as catalyst led to the establishment of the general and highly enantioselective formal alkenylation of N-benzoyl imines [77]. Since the oxidative transformation of an aza-enamine moiety of the product into a nitrile functionality appeared feasible as described above, this method offered facile access to optically active y-amino a,P-unsaturated nitriles (Scheme 7.50). 

MBH Reaction of Aromatic Trifluoromethyl Ketones. The MBH reaction of hexafluoroacetone and the corresponding N-benzoyl imine is known (Scheme 7) (iO). We were engaged in the reaction of pe uoroalkyl alkyl and aryl ketones due to our interest in asymmetric syndiesis of fluoroalkyl allylic alcohols. 

Ojima, 1., Habus, 1., Zhao, M. (1991) Efficient and Practical Asymmetric Synthesis ofthe Taxol C-13 Side Chain, N-Benzoyl-(2R,3S)-3-phenylisoserine, and its Analogues via Chiral 3-Hydroxy-4-aryl-b-lactams Through Chiral Ester Enolate-Imine Cyclocondensation. Journal of Organic Chemistry, 56, 1681-1683. 

Since the last review in this series in 1993 (10) and the publication of Ojima s paper summarizing his approach to the / -lactam (237), a number of new approaches for the asymmetric synthesis of the / -lactam taxol side chain have emerged. For example, chiral sulfonamide esters have been used as chiral auxiliaries to achieve diastereoselective cycloaddition with N-TMS-imine, to give lactam 7.1.1 in 94% yield. Benzoylation of 7.1.1 yielded the ready-to-couple lactam 7.1.2 in 96% yield (238). 

It was originally suggested by Swindell that acylation of baccatin III with protected N-benzoyl-3-phenylisoserine proceeds through an oxazinone intermediate (286). He then developed a synthesis of the side chain methyl ester by hydrolysis of a protected oxazinone intermediate 7.6.3, which was itself prepared in 70% yield by a Diels-Alder type reaction between the imine 7.6.1 and the chiral ketene acetal 7.6.2. Hydrolysis of 7.6.3 and removal of protecting groups gave the side chain methyl ester in 93% yield (287). 

On the other hand, diaryl prolinol silyl ethers have been applied as orga-nocatalysts for the asymmetric Mannich reaction of acetaldehyde with N-benzoyl-, iV-Boc- and iV-Ts-imines in the presence of para-aiirobtnzoic acid in THF. The generated (3-amino aldehyde products were isolated in good to high yields and excellent enantioselectivities (95-98% ee) after conversion into the corresponding alcohols by reduction with L1A1H4 (Scheme 3.10). 

With respect to cupreidine, C9 0-benzoyl esters of this cinchona derivative were demonstrated to be the best catalysts for the nitroaldol reaction of a-ketoesters [55], the conjugate addition of anthrone to nitroalkenes [56], the Henry reaction with fluoromethyl ketones (Scheme 6.25) [57], and an aza-Friedel-Crafts reaction of naphthols with N-sulfonyl imines [58]. 

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]. 

Ph, R = NHj, with phosgene gives a novel bicyclic heterocyclic system which can be represented as a bicyclic meso-ionic l,3,4-thiadiazol-2-one (493) (Section VII,H,1). A similar reaction using A -benzoyl isocyanide dichloride (PhCO.N=(i Cl2) gives the novel meso-ionic 1,3,4-thiadiazol-2-imine (494) (Section VII,H,2). ... 

A general synthetic route to meso-ionic N-acyl-1,3-thiazol-5 -imines (108, R1 = Ph, R2 = Me, R3 = Me or Ph, R4 = COPh) is provided by treatment of thiobenzamidoaminoacetonitriles, Ph-CS-NMe-CHR-CN, first with benzoyl chloride and then with aqueous alkali. Alternatively, the thiobenzamidoaminoacetonitriles and hydrogen chloride give the corresponding salts, which with benzoyl chloride and aqueous alkali give A-acyl-l,3-thiazol-5-imines (108).39b,67b... 

However, an ElcB-type process was reported as a novel mechanism for hydrolysis of a /3-sultam. In the case of the N-a -methoxycarbon y I /3-sultam, deprotonation of the acidic exocyclic hydrogen leads to the formation of a carbanion, which then undergoes a rate-limiting conversion to a ring-opened species with expulsion of a sulfinate anion. Then, hydrolysis of the imine species produces benzoyl formate as the principal product detected (Scheme 14) <2002CC772>. 

Chiral Imidazolidinones with Other Substitution Patterns. The intermediate imidazolidinone (2) can also be N-acylated by Benzoyl Chloride or Benzyl Chloroformate, and other substituents on the acetal center and/or on the N(3) nitrogen can be present, depending upon the aldehyde used for the imine formation and upon the glycine amide employed at the beginning of the synthesis. Chiral substituents, such as the 1-phenylethyl group may be placed on N(3), and the imidazolidinone may be derived from a dipeptide. Some examples are collected for (15), with references, in Table fijesg different derivatives... 

---