P-Thiolactams

The p-thiolactams 50 are obtained by the action of Lawesson s or Davy s reagent on 3-substituted 1-methoxy- or 1-benzyloxy-azetidinones followed by reductive N-deprotection. The simple P-thiolactam can be modified to give the thiolactam analogues of monobactams <96LA141>. 

Acyl thioamides react with lithium diisopropylamide (LDA) to give p-thiolactams (Scheme 30).57... 

When the solid sample of 24a was irradiated at 0 °C, the crystals gradually changed to amorphous. At this point, the generation of 25a was not observed (Scheme 14 and Table 9, entry 1), and only a mixture of (E) and (Z) isomers (Z/ =1.5) was obtained [47,48]. Prolonged irradiation gave P-thiolactam 25a in 54% yield (entry 2). 

In the solid-state photoreaction of 24c, a more chemoselective reaction occurred and only p-thiolactam 25c was obtained almost quantitatively. Of particular importance is the finding that the solid-state photoreaction of 24c involves a crystal-to-crystal nature where the optically active p-thiolactam 25c is formed in specific yield. Furthermore, the X-ray crystallographic analysis revealed that the crystals of 24c are chiral, and the space group is P2j. Irradiation of crystals at 0 °C exclusively gave optically active P-thiolactam 25c, in 81% yield at 100% conversion (entry 5). As expected, the thiolactam 25c showed optical activity (81% ee). This reaction exhibited good enantioselectivity throughout the whole reaction, where a small difference was observed in the ee value from 97 to 81% ee with increasing conversion from 20 to 100% (entries 5 and 6). The solid-state photoreaction also proceeded without phase separation even after 100% reaction conversion. The crystal-to-crystal nature of the transformation was confirmed by X-ray diffraction spectroscopy. 

Photolysis of cycloheptenecarbothioamide 24d in the solid state also gave the corresponding p-thiolactam in specific yield (entry 7). As the X-ray crystallographic analysis revealed, the crystal is racemic (Fig. 9), and the isolated p-thiolactam was obtained as racemate. 

When thioamides 24f-h were irradiated in benzene with a high-pressure mercury lamp, iV-isopropyl-P-thiolactam 26 and 1,3,5-dithiazine 28 were obtained (Scheme 15 and Table 10, entries 1,3, and 5). Considerably different photochemical behavior was observed between that in solution and in the solid state. Powdered thioamide 24f was irradiated in the solid state at 0 °C until 19% conversion, because the solid changed to amorphous at around 20% conversion. In this case, only dithiazine 28f was obtained as the sole photoproduct (entry 2). On the contrary, photolysis of 24g gave a new type of p-lactam 27g as a main product in 88% yield in addition to dithiazine 28g (12%) the P-lactam 26g was not detected at all (entry 4). Photochemical ( ,Z) isomerization of (Z)-24g was also observed in the early stage of the reaction, where the ratio of the photostationary state was ZIE=1.9. In the case of 24h, P-thiolactam 27h was ob-... 

From carboxylic esters or amides 6-64 Addition of imines to thioketenes (P-thiolactams)... 

X-ray crystallographic analysis revealed that the crystals of thioamide 32b are chiral and the space group is P2 L lx. Dextrorotatory crystals were irradiated at 0°C until the reaction conversion reached 81 % yield. As expected, the asymmetric induction was observed, and optically active 33b (55% ee) was isolated (Table 5). As a consequence of the suppression of the reaction conversion yield from 81% to 17%, the enantiomeric purity rose up to 74% ee. p-Thiolactam 33b with only Z-configuration was isolated, and the absolute configuration of ( + )-33b was determined as (3S,4S)-isomer by the x ray anomalous scattering method. 

In the solid-state photoreaction of 32c, a more chemoselective reaction occurred than in solution, and only p-thiolactam 33c was obtained almost quanti-... 

Irradiation of asymmetrically substituted A -benzyl-A -isopropyl-aP-unsatu-rated thioamides (102) in benzene solution induces hydrogen abstraction by the alkenyl carbon from the benzyl and isopropyl groups to give a P-thiolactam (103) and 1,3,5-dithiazinane (104) as products. In the solid state, however, photolysis causes hydrogen abstraction from only the isopropyl group to give the isomeric P-thiolactam (105). 

An interesting crystal-to-crystal asymmetric photoreaction of a, 3-unsaturated thioamide to p-thiolactam (Scheme 5.53) with 94% ee in 96% yield of 58% conversion was reported by Sakamoto et al2 ... 

Heterocycles. New syntheses of pyrroles and P-thiolactams have been reported. A synthesis of the antibiotic (-)-dysidazirine features an elimination of an Af-toluenesulfinylaziridine. Remarkably, the deprotonation is not at the a-carbon of the ester group. 

Reviews of P-lactam synthesis by ester-enolate addition <96MI119>, of p-thiolactams <97MI349> and of P-lactam chemistry <96MI 1002, 96MII003, 97MI1002> have appeared. 

Alknyl silyl sulfides, R CsCSSiR s, which are readily obtained by silylation of anions (39), react as thioketene equivalents. Thus, p-thiolactams are formed in the reaction with C—N systems (c/. Volume 5, Chapter 2.2)- and thioamides on addition of amines equation (18) shows a typical example. This approach has great promise for the thioacylation of very sensitive natural products. 

Cyclic amidinium salts (71) are obtained by [2 + 2] cycloaddition of ketenimmonium compounds (69) to Schiff bases (70 R = H, Me02C) or thioimidates (70 R = SBn) their thiolysis provides an elegant access to p-thiolactams (72 equation 32). ... 

With linear atnidines, t-buty(i-propyl)thioketene reacts across its C=N bond to give p thiolactams. Also, a,j8-unsaturated itnines 44 react with thioketenes to give the y3-lactam cycloadducts 45" . 

Sakamoto, M., Takahashi, M., Arai, W., Mino, T., Yamaguchi, K., Fujita, T., and Watanabe, S., Solid-state photochemistry absolute asymmetric P-thiolactam synthesis from achiralN,N-dibenzyl-a,P-unsaturated thioamides, Tetrahedron, 56, 6795, 2000. 

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