P-lactam formation

Azolium enolates such as 65 can be generated directly through addition of NHCs to symmetrical or unsymmetrical ketenes. For example, Smith and co-workers have shown that NHC promoted p-lactam formation from isobutylphenylketene 61 and AT-tosyl imines 63 proceeds with good yields and moderate levels of diastereoselec-tivity via enolate 65 (Scheme 12.12) [17]. 

Scheme 12.57 Rationale for enantio- and diastereoselective P-lactam formation...

To explain the formation of p-lactam formation two plausible mechanisms have been suggested (Scheme 2.320). 

The mechanism of p-lactam formation is thought to involve photoinduced electron transfer from nitrogen to the benzoyl group followed by transfer of a tertiary y-proton from one of the isopropyl groups to the carbonyl oxygen... 

An interesting bifunctional system with a combination of In(OTf)3 and benzoyl-quinine 65 was developed in p-lactam formation reaction from ketenes and an imino ester by Lectka [Eq. (13.40)]. High diastrereo- and enantioselectivity as well as high chemical yield were produced with the bifunctional catalysis. In the absence of the Lewis acid, polymerization of the acid chloride and imino ester occurred, and product yield was moderate. It was proposed that quinine activates ketenes (generated from acyl chloride in the presence of proton sponge) as a nucleophile to generate an enolate, while indium activates the imino ester, which favors the desired addition reaction (66) ... 

Mechanism of P-Lactam Formation with Polyaromatic Imines... 

Chiral crystals formed from chiral molecules can undergo highly diastereoselec-tive photoreactions, while diastereodifferentiation in solution is usually low. Here three types of diastereoselective photoreactions in the crystalline state are presented. Highly diastereoselective Norrish/Yang photocyclization of adamantane [36] and p-lactam formation from oxoamides [37] have been also reported. 

Cycloadditions. The scope of the Evans asymmetric aziridination is broadened by the ready availability of nitrene precursor 4-02NCjH S02N=IPh. The oxazolidinone-Af-acetic acid derived from (+)-cw-2-amino-l,2-diphenylethanol participates in p-lactam formation with imines. The predominant products (>99 1) have the (3/f,45)-configuration. The intramolecular [2+2]photocycloaddition involving a chiral allenylsilane moiety is an excellent method for accessing optically active methylenecyclobutane derivatives. ... 

Lynch, J. E. Riseman, S. M. Laswell, W. L. Tschaen, D. M. Volante, R. P. Smith, G. B. Shinkai, I., Mechanism of an Acid Chloride-Imine Reaction by Low-Temperature FT-IR P-Lactam Formation Occurs Exclusively through a Ketene Intermediate. / Org. Chem. 1989,54,3792. 

P-Lactam formation on a triazene dipeptide-derivatized resin (Scheme 45) [273] ... 

Finally, the enantioselective bicyclo-P-lactam formation, via direct annulation of enals and unsaturated N-solfonyl ketimines using N-mesityl-substituted triazolium chloride (in the presence of bases in organic solvents) as pre-catalyst, has been investigated by W. Bode et al. [98]. 

Jiao L, Liang Y, Xu J (2006) Origin of the relative stereoselectivity of the p-lactam formation in the Staudinger reaction. J Am Chem Soc 128 6060-6069... 

He M, Bode JW (2008) Enantioselective, NHC-catalyzed bicyclo-P-lactam formation via direct annulations of enals and unsaturated N-sulfonyl ketimines. J Am Chem Soc 130 418-419... 

Of the two catalysts investigated, Rh2(4S-MEOX)4 gave significantly higher enantioselectivity (up to 78% ee) than Rji2(5S-MEPY)4. When the W-alkyl group at the 2-position is a carboxylate group as in Eq. (49), P-lactam formation occurs in moderate ee (46%), but here there is competition from an alternative C-H insertion into the ferf-butyl substituent. 

The mechanism of p-lactam formation in enolate-imine condensations proceeds by the stepwise pathway depicted in Scheme 19, in which diastereomeric P-lactams (100) and (101) are formed by cycliza-tion of intermediate, metalated amine adducts (98) and (99), respectively. The possibility of a less likely [2 + 2] cycloaddition mechanism has been discussed.88,89 Equilibration between p-lactams (100) and (101) via epimerization at C-3 does not normally occur.88 The stepwise mechanism is supported by the fact that trans P-lactam (101 R1 = Pr R2 = R3 = Ph) is formed from (99 M = MgBr) without loss of... 

Many polycyclic aromatic amines and aldehydes are commercially available, but their supply is very limited. Preparation of these starting materials is necessary for studying the p-lactam formation reaction [93]. Nitro compounds are the precursors for the amines. An important task was to prepare polycychc aromatic nitro compounds, particularly those of chrysene, phenanthrene, pyrene, and dibenzofluorene in good yield. Nitration of these hydrocarbons with concentrated nitric acid in sulfuric acid is a widely used reaction for this purpose. Our research culminated in facile synthesis of polyaromatic nitro derivative 9 starting from polyaromatic hydrocarbons (PAHs) 8 through the use of bismuth nitrate impregnated with clay (Scheme 1) ([94, 95] for some examples of bismuth nitrate-catalyzed reactions... 

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