Imines lactams, with rearrangement

Cyclic imines from lactams with rearrangement... 

Abstract The photoinduced reactions of metal carbene complexes, particularly Group 6 Fischer carbenes, are comprehensively presented in this chapter with a complete listing of published examples. A majority of these processes involve CO insertion to produce species that have ketene-like reactivity. Cyclo addition reactions presented include reaction with imines to form /1-lactams, with alkenes to form cyclobutanones, with aldehydes to form /1-lactones, and with azoarenes to form diazetidinones. Photoinduced benzannulation processes are included. Reactions involving nucleophilic attack to form esters, amino acids, peptides, allenes, acylated arenes, and aza-Cope rearrangement products are detailed. A number of photoinduced reactions of carbenes do not involve CO insertion. These include reactions with sulfur ylides and sulfilimines, cyclopropanation, 1,3-dipolar cycloadditions, and acyl migrations. 

In 2001, diazoketones [169, 170] derived from suitably protected amino acids have been reported to be photochemically rearranged in the presence of imines leading exclusively to //c/n.v-substitiited (3-lactams with up to 84% yield [171]. Selectivities were dependent on the steric demand of the amino acid side-chain with dr ranging from 65 35 to 90 10, (Scheme 70). 

A Lewis acid-induced aza-Diels-Alder reaction between the /3-lactam-imine 295 and 3,4-di hydro-2//-pyran gives the two diastereomeric pyranoquinolines 296 and 297. Under basic conditions, these products rearrange to the amino-substituted pyranoindolizinones, 298 and 299, respectively, with retention of stereochemistry (Scheme 74) <2003CEJ3415>. 

Scheme 61, yielded thiazole 200 as the major product, along with minor amounts of carbinol 201 [152]. On the other hand, treatment of the imine formed from 199 and p-methoxyphenylamine with catalytic tetrabutylammonium cyanide, produced suc-cinimide derivative 202. In both cases, the process is initiated by nucleophilic attack to the carbaldehyde C=0 (or azomethine s C=N) group, which is followed up by an anionic rearrangement. A variation of the above process using as catalysts /V-heterocyclic carbenes (NHC) derived from base treatment of azolium, imidazo-lium, or triazolium salts, has also been developed to access gem-disubstituted succinimides [153, 154]. Unfortunately, an attempt of kinetic resolution of racemic 4-formyl (3-lactams by using chiral NHC resulted in moderate selectivities only [154]. 

The lithium amides 98, prepared from 4-hydroxy—lactone and imines, rearranges in the presence of lithium chloride at low temperature to form -lactams 99 (Scheme 52) with cholesterol absorption inhibition properties <1999JOC3714, CHEC-III(2.01.3.10.10)69>. 

RCH=C=0, except when these are generated in situ by decomposition of a diazo ketone (the Wolff rearrangement, 18-8) in the presence of the imine. It has been done with ketene, but the more usual course with this reagent is an addition to the enamine tautomer of the substrate. Thioketenes ° (R2C=C=S) give p-thio-Imines also form p-lactams when treated with (i) zinc (or another... 

Bicyclic lactams 22 with an incorporated cyclopropylamine unit were formed in the three-componenl reaction of pentacarbonyl(dimethylaminocarbene)chromium(0) (21) with di-phenylacetylene and imines. The products, of course, are not formed by way of a cyclo-propanation step of the carbene unit, but rather by way of an intermediately formed coordinated enamino ketone which is trapped in situ by the imine. Instead of the expected [2-1-2] or [4-1-2] cycloadducts, bicyclic lactams are produced through a multistep rearrangement process. 

An elegant method for the solid-phase synthesis of quinolinone 9 derivatives has been developed by Pei et al. [43]. Using the teabag technology, the synthesis of a 4-amino-3,4-dihydro-2(l//)-quinolinone library was carried out through the rearrangement of /3-lactam intermediates on the solid phase. The condensation of o-nitrobenzaldehyde with a resin-bound amino acid yielded an imine that, following [2-1-2] cycloaddition with ketenes, afforded the -lactams (Fig. 3g). 

An intermolecular cyclization approach to C3 asymmetric oxindoles has been devised by Smith and coworkers who paired chiral A-phenylnitrone nucleophiles with ketene electrophiles, e.g., intermolecular fusion of 54 and 55 [37]. As illustrated in Scheme 16, the oxindole skeleton 57 materialized in 87% ee following a proposed sequence of nitrone addition to the ketene, a hetero-Claisen rearrangement, imine hydrolysis and, finally, cyclization to generate the lactam linkage. As an extension of this methodology, (5)-3-allyl-3-phenyloxindole 57 was transformed into enantiopure 3-phenyl-hexahydropyrroloindole scaffold 58. 

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