Cycloaddition reactions imines

Asymmetric synthesis of 3-amino (3-lactams via Staudinger ketene-imine cycloaddition reaction 98KGS1448. 

In an analogous late-stage arylation approach, terminal alkyne 31 was envisioned as a versatile intermediate. Slow addition of 4-pentynoyl chloride to imine 3 and (n-Bu)3N at reflux (efficient condenser, 100°C, 12 h, 1 1 toluene heptane) afforded only trace amounts of 31. Reaction of 4-pentynoyl chloride with triethylamine in methylene chloride under preformed ketene conditions ( 78°C, 1 h), followed by addition of 3 and warming to — 10°C over 4 h, afforded a complex mixture of products. Since high-yield preparation of 31 remained elusive, access to internal alkynyl analogs (type 33) was accomplished by preassembly of the appropriate arylalkynyl acid substrate for the ketene-imine cycloaddition reaction (Scheme 13.9). 

Reviews including aspects of P-lactam chemistry are ketene-imine cycloaddition reactions <98CHE1222>, radical cyclization processes <98MI169>, combinatorial synthesis <98AJC875>, electrophilic cyclization of unsaturated amides <98T13681> and theoretical studies on the synthesis of P-lactams <98MI245>. 

Ketene-imine cycloaddition reactions of ethoxycarbonyl(phenylthio)ketene with various imines and subsequent desulfurization reactions have been reported in 2006 to synthesize 3-ethoxycarbonyl (3-lactam derivatives [108]. 

The past decade has witnessed considerable interest in solvent-free ketene-imine cycloaddition reactions employing microwave irradiation (Equation 203) C1995TL213, 1996TL6989, 1997H(44)405, 2005JOC334, 2005IJB2093>,... 

An efficient use of triphosgene, as an acid activator, for the synthesis of substituted 2-azetidinones via ketene-imine cycloaddition reaction using various acids and imines has been achieved <02T2215>. Novel routes to monocyclic (3-lactams 13 and 14 through the photochemical decomposition of oxime oxalate amides <02CC2086> and a-oxoamides <02OL1443> have also been described. 

THEOCHEM), in press. Electrostatic Solvent Effect on the Ketene—Imine Cycloaddition Reaction. 

Palomo, C. Aizpurua, J. M. Ganboa, I. Oiarbide, M. Asymmetric Synthesis of P-Lactams by Staudinger Ketene-Imine Cycloaddition Reaction, Eur. J. Org. Chem. 1999, 3223-3235. 

VII. Methylseleno-Promoted Ketene-Imine Cycloaddition Reaction. 30... 

A new methylseleno-promoted ketene-imine cycloaddition reaction between 151 and 152 (86JOC4737) gave the bicyclic product 153 in an extremely high stereoselective fashion and in fairly good yield (36-92%) (Scheme 27). 

The reaction between methoxyacetyl chloride and (4/ )-155 or (4/ )-157 gave the corresponding bicyclic product in a moderate yield [58% in (4/ )-155] or in a very poor yield [5% in (4/ )-157] (compared to the 81% yield of 153a). Thus, a methylseleno substituent on the imine moiety promoted this ketene-imine cycloaddition reaction. 

Georg, G. I., Ravikumar, V. T. Stereocontrolled ketene-imine cycloaddition reactions. Org. Chem. fi-Lactams 993, 295-368. 

Palomo, C., Aizpurua, J. M. Asymmetric synthesis of 3-amino-P-laclams via Staudinger ketene-imine cycloaddition reaction. Chem. Met. Comp. (New York) (Translation of Khim. Geterot. Soed.) 1999, 34,1222-1236. 

Sordo, J. A., Gonzalez, J., Sordo, T. L. An ab initio study on the mechanism of the ketene-imine cycloaddition reaction. J. Am. Chem. Soc. 

Palomo C, Aizpurua JM, Ganboa 1, Oiarbide M (1999) Asymmetric synthesis of P-lactams by Staudinger ketene-imine cycloaddition reaction. Eur J Org Chem 1999 3223-3235... 

The synthesis of optically active thiazolo[3,2-fl]pyridinones has been described. Chiral thiazolines 27, prepared from the condensation of imino ethers 25 with (R)-cysteine methyl ester 26, undergo a ketene-imine cycloaddition reaction with Meldrum s acid derivatives 28 to give thiazolo[3,2-a]pyridinones 29 in good yields <01JOC6756>. 

Neooctams, such as the unsubstituted parent compound (191), are easily obtained in cycloadditions. Isocyanates [125,126], sulphonyl isocyanates (43) [29,127] and especially chlorosulphonyl isocyanate (189) [128] react with alkenes to form variously-substituted j3-lactams [129—135]. Synthesis of compound (191) is an example of this reaction which has been discussed in detail [52]. The same compound (192) can be obtained in the photolytic rearrangement of the pyrazolone (194) [136]. Compound (196) is neooctam-5,7-diene, obtained from the azocine (195) and hydrogen bromide [137]. Lactam (196)is a partly saturated form of (199). The latter is an unstable neooctam derivative, formed in an intramolecular ketene-imine cycloaddition reaction (see (198))... 

The mechanism of the Staudinger ketene imine cycloaddition reaction has been the subject of much debate and has recently been reviewed. The mechanism has been studied both computationally and experimentally. Experimental evidence gathered on solution phase reactions supports a two-step mechanism, in which addition of the imine nitrogen to the ketene carbonyl group occurs to generate an intermediate zwitterion. Subsequent cyclization of the zwitterion results in formation of the key C3-C4 a-bond. 

Triphosgene activation has been used for the construction of ) -lactams through ketene-imine cycloaddition reactions (Staudinger reaction) [1030]. In all the studied cases, the cydoaddition reaction was found to be stereoselective and only cis- 8-lactams 1362 were formed. 

Georg GI, Ravikumar VT. Stereocontrolled ketene-imine cycloaddition reactions. In Georg GI, editor. The organic chemistry of fi-lactams. New York VCH 1992. p 295-368. 

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