Synthesis of thiazolines

Thiazolines can also be obtained through cyclodehydration of the compounds bearing C(=S)-NH-C-C-OH moiety (P-hydroxy thioamide). The utility of this strategy is demonstrated in the total synthesis of siomycin A, a member of the thiostrepton family 07TL1331 . Exposure of thioamide 77 with DAST results in intramolecular cyclization to provide an excellent yield of thiazoline 78, which is converted to siomycin A in four steps. Compound 77 represents one of the most complex substrates for DAST-induced thiazoline formation. 

The intramolecular aza-Wittig reaction of azidothioesters provides a new approach to functionalized thiazolines 07AG(E)2701 . Coupling of protected amino acids 79 with azido thiols 80 provides thioesters 81, which are treated with triphenyl phosphine to afford thiazolines 17 in good yields. Similarly, the bis(thioester) 82 is converted into the bis(thiazoline) 19. These thiazolines are readily oxidized to the corresponding thiazoles (vide supra). 

Compounds bearing C(=S)-NH-C-C-OH fragment ((3-hydroxy thioamide) can also undergo cyclodehydration to form thiazoline derivatives. The utility of this strategy has been demonstrated in the synthesis of halipeptins A and D 06JA4460 . Exposure of 73a/b with (diethylamino)sulfur trifluoride (DAST) brings about intramolecular cyclization to provide thiazolines 74a/b, which are advanced precursors to halipeptins A and D. 

As described previously, thiazohnes are versatile intermediates to thiazoles. In addition, thiazoline rings are structural motifs found in numerous natural products. Among a variety of methods for the construction of thiazolines, the cyclodehydration protocol is perhaps most popular. In the total synthesis of cyclopeptide YM-216391, (diethylamino)sulfur trifluoride (DAST) is used as the cyclodehydrating agent for the conversion of P-hydroxy thioamide 76 to thiazoline 13 05CC797 . A similar strategy has been used in the construction of the thiazoline moiety in two independent total syntheses of hahpeptin A (77 to 78 79 to 80) 

In the total synthesis of didmolamides A and B, the thiazoline moiety is formed from the trityl protected cysteine 83 by a nucleophilic attack of the cysteine thiol group on the phosphorus-activated amide carbonyl group of the preceding residue (see 84) 05TL2567 . 

2-Imino-thiazolidine 93 is prepared directly from the corresponding (9-methanesulfonyl (3-amino alcohol hydrochloride 89 using potassium thiocyanate via aziridine intermediate 90 05TL233 . Ring opening of 90 with potassium thiocyanate gives amines 91 and 92, which recyclizes to furnish the same cis itnine 93. 

A series of l-acylimino-3if-thiazoline derivatives 104 are prepared by a one-pot three-component condensation of arylisothiocyanates 100, primary amines 101 and a-halocarbonyl derivatives 102 presumably via intermediates 103 05TL419 . 

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You, S.-L., Razavi, H. and Kelly, J.W. (2003) A biomimetic synthesis of thiazolines using hexaphenyl-oxodipho-sphonium trifluoromethanesulfonate. Angewandte Chemie (International Edition in English), 42, 83—85. 

A new synthesis of thiazolines has been described. The annulation of thioamides with 2-alkynoates or 2,3-dienoates in the presence of a phosphine catalyst yields thiazolines in a selective manner <02JOC4595>. 

The synthesis of thiazoline based nucleosides has been reported. The synthesis starts with methyldifluorodiethoxyphosphonodithioacetate (79), which is coupled with P-aminoalcohols to... 

Synthesis of thiazoline 278 in excellent yield and with high enantioselectivity was accomplished from fully protected cysteine 277 using the Ph3P0/Tf20 reagent (Scheme 135) <2003AGE83, CHEC-III(4.06.9.2.8)690>. 

Synthesis of thiazoline 201 was accomplished from fully protected cysteine 202 using PhsPO (3.0equiv) and Tf20 (l.Sequiv) to generate an oxophilic Lewis acid catalyst 203 in solution. The reaction gave 201 in 98% yield and >99.5% ee <2003AGE83>. The proposed mechanism is shown in Scheme 79. 

Synthesis of thiazolines from ketones, sulfur and NH3 with the possibility to obtain thioketones. 

Fukuyama and Xu" reported the first total synthesis of (—)-tantazole B 1188b (Ri = R2 = CH3) in 1993. This synthesis also corrected the originally assigned stereochemistry of the methyl group in ring E. The authors discovered a novel and versatile synthesis of thiazolines 1314 via cyclodehydration of ammonium thiol esters 1313 and adapted this methodology to prepare 1188b (Scheme 1.337). 

A complex hydrolysis-elimination-rearrangement of 2-oxo-azetidin-4-thiones induced by silica (e.g. equation 4.17) is used in the synthesis of thiazolines [92]. 

Intramolecular aza-Wittig ring closure is applied to the synthesis of thiazolines from P-azido thioesters 43, which are readily obtained from amino acid derivatives (13EJOC3290). Treatment of thioester 43 with... 

Several alternate pathways for the synthesis of thiazoline azetidinones have been reported however, none appear to be as efficient as the initial synthesis. Rearrangement of the thioamide (210), prepared either by direct acylation or by treatment of the iminochloride (211) with hydrogen sulfide, gave an initial unstable product (212) which decomposed under a variety of conditions to give 213 as the major product (Tanida et al., 1975b,c). 

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