Thiolactams synthesis

Crystal-to-Crystal Solid-State Photochemistry Absolute Asymmetric (3-Thiolactam Synthesis from an Achiral a,(3-Unsatur ated Thioamide, J. Am. Chem. Soc. 118, 10664-10665. (b) Sakamoto, M., Takahashi, M., Arai, W., Mino, T., Yamaguchi, K., Watanabe, S., and Fujita, T. (2000) Solid-State Photochemistry Absolute Asymmetric (3-Thiolactam Synthesis from Achiral N,N-Dibenzyl-a,6-unsaturated Thioamides, Tetrahedron, 56, 6795-6804. (c) Hosoya, T., Ohhara, T., Uekusa, H., and Ohashi, Y. (2002) Crystalline-state... 

The efficiency of a bis(disilyl)sulfide for thiolactam synthesis has been explored prior activation of the amide into a Vilsmeier type intermediate was necessary [32]. 

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. 

The high nucleophilicity of sulfur atoms is preserved, even if it is bound to electron withdrawing carbonyl groups. Thiocarboxylales, for example, substitute bromine, e.g. of a-bromo ketones. In the presence of bases the or-acylthio ketones deprotonate and rearrange to episulfides. After desulfurization with triphenylphosphine, 1,3-diketones are formed in good yield. Thiolactams react in the same way, and A. Eschenmoser (1970) has used this sequence in his vitamin B]2 synthesis (p. 261). 

Schemes 15 and 16 summarize the syntheses of intermediates that represent rings A and D of vitamin Bi2 by the Eschenmoser group. Treatment of lactam/lactone 51, the precursor to B-ring intermediate 8 (whose synthesis has already been described, see Scheme 8), with potassium cyanide in methanol induces cleavage of the y-lac-tone ring and furnishes intermediate 76 after esterification of the newly formed acetic acid chain with diazomethane. Intermediate 76 is produced as a mixture of diastereomers, epimeric at the newly formed stereocenter, in a yield exceeding 95%. Selective conversion of the lactam carbonyl in 76 into the corresponding thiolactam...

Following a similar strategy, the synthesis of tetracyclic models of aziridinomitosenes, bioactive degradation products of mitomycins, was based on the Reformatsky reaction of thiolactam 100, as shown in equation 59. The synthetic plan and reagent design were directed to the use of an intramolecular Heck reaction of 101 to complete the target skeleton146. 

Scheme 28 outlines Eschenmoser s model corrin synthesis. The enamide (310) was treated with KCN to give (311), and this gave the thiolactam (312) when treated with phosphorus pentasulfide. Benzoyl peroxide oxidation yielded the disulfide (313), and in the presence of the enamide (310) this gave the bicyclo thio-bridged compound (314). Sulfur extrusion, by this time a standard procedure (Scheme 22), provided the vinylogous amidine (315)... 

In the total synthesis of indolizomycin700, one of the key steps involved the cyclization of a thiolactam with an intramolecular a-di azoketone moiety, catalyzed by rhodium acetate (equation 195). The molecule is desulfurized by treatment with Raney nickel, giving a good yield of the required target. 

In this reaction, achiral A-methacryloylthiobenzanilide 39 gave chiral crystals by spontaneous crystallization, and absolute asymmetric synthesis was performed by the solid-state photoreaction leading to optically active thietane-fused 3-thiolactam. The reaction mechanism for the cyclization was elucidated on the basis of the correlation between the absolute structures of both the prochiral starting monothioimide and the photoproduct. 

The known pentacyclic lactam (219), prepared from 2-hydroxytryptamine and dimethyl 4-ethyl-4-formylpimelate, has been used in an improved synthesis of ( )-quebrachamine.106a Conversion of (219) into the thiolactam, acetylation to (220), desulphurization, and hydrolysis yielded 1,2-dehydroaspidospermidine (221), which on reduction gave ( )-quebrachamine (222) (Scheme 31). A new synthesis of the tetracyclic amino-alcohols (223) constitutes another formal synthesis of quebrachamine.1066... 

In a recent application, cw-aminoindanol has been employed as a rigid diastereocontrol element in the alkylation of bicyclic lactams and thiolactams of which they are a component. The resulting products form the basis of an enantioselective synthesis of alkaloids. 

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