Halogen-dance reaction

Oxidation of thiophene with Fenton-like reagents produces 2-hydroxythiophene of which the 2(570 One isomer is the most stable (Eq. 1) <96JCR(S)242>. In contrast, methyltrioxorhenium (Vn) catalyzed hydrogen peroxide oxidation of thiophene and its derivatives forms first the sulfoxide and ultimately the sulfone derivatives <96107211>. Anodic oxidation of aminated dibenzothiophene produces stable radical cation salts <96BSF597>. Reduction of dihalothiophene at carbon cathodes produces the first example of an electrochemical halogen dance reaction (Eq. 2) <96JOC8074>. 

The halogen dance reaction with base on 2-thiazolamine systems has been reported giving access to 5-substituted 4-bromo-2-thiazolamine derivatives (Scheme 60). The dance reaction is a favoured process and prevention is only possible when optimized reaction conditions and selected electrophiles are applied.95... 

The DE ring of camptothecin has been prepared enantioselectively in six steps from 2-fluoropyridine using a halogen dance reaction <95TL(36)7995>. The first total synthesis of dimethyl sulfomycinamate (47) was reported starting from 3-hydroxy-6-methylpyridine (48) <95TL(36)5319>. 

As with carbocyclic rings, the usual rules apply for avoiding deprotonation (and rearrangement) and promoting metallation low temperatures and t- orn-BuLi as base.94 LDA is used when deprotonation is required (the example below contrasts the deprotonation and halogen-metal exchange of 104) and the halogen dance reactions described in section... 

Scheme 24. Tandem DoM/halogen dance reactions of iodopyridines.

The halogen dance reaction is also applied to the synthesis of the 5-substituted 4-bromo-2-chlorothiazole derivatives 89 <07SL3016>. Treatment of 5-bromo-2-chlorothiazole with 1.2 equiv. of LDA at -80 °C brings about full conversion to the halogen dance product 88, which is trapped with various electrophiles to give the 5-substituted thiazoles 89. For example, 4-bromo-5-trimethylsilyl-thiazole is obtained in 71% yield when 5-bromo-2-... 

Miyaura, N., Suzuki, A. Palladium-Catalyzed Cross-Coupling Reactions of Organoboron Compounds. Chem. Rev. 1995, 95, 2457-2483. Sammakia, T., Stangeland, E. L., Whitcomb, M. C. Total Synthesis of Caerulomycin C via the Halogen Dance Reaction. Org. Lett. 2002,4, 2385-2388. 

While the so-called halogen dance reaction had been reported for aromatic and heteroaromatic systems, it had never been described for the oxazole ring. This approach was used for an efficient transformation of 5-bromo-2-phenyloxazole, 114, into several 5-substituted 4-bromo-2-phenyloxazoles 115 <05SL1433>. The electrophiles used were water, benzaldehyde, TMSCl, halogens, and CO2 affording the final compounds in good yields (66-78%). 

FUNCTIONALIZATION OF PYRIDINES AND THIAZOLES VIA THE HALOGEN-DANCE REACTION, APPLICATION TO THE TOTAL SYNTHESIS OF CAERULOMYCIN C AND WS75624 B... 

This article describes strategies for the use of the halogen-dance reaction in the functionalization of aromatic heterocycles, and the synthesis of two pyridine-derived natural products, caerulomycin C and WS75624 B (Figure 1). The origins of this research lie in the... 

A typical halogen-dance reaction from the work of Queguiner is shown in Scheme 7. In this example, treatment of 2-fluoro-3-iodopyridine (18) with LDA and methyl iodide provides pyridine 19, in which the iodine has migrated to the 4-position and a methyl group has been incorporated at the 3-position. The mechanism of related halogen-dance... 

IV. Early Efforts, Limitations to the 1,3-Halogen-Dance Reaction... 

V. Successful 1,3- and 1,4-Halogen-Dance Reactions, Synthesis of the Core Pyridine Structure... 

VII. Completion of the Synthesis of WS75624 B, Application of the Halogen-Dance Reaction to Thiazoies. 

Completion of the synthesis of WS75624 B was more complicated than that of caerulomycin C due to the presence of the substituted thiazole. As previously mentioned, our retrosynthetic analysis involved the disconnection of the thiazole from the pyridine, and required that we synthesize an appropriately functionalized thiazole coupling partner bearing a metal at the 4-position. Our success with the halogen-dance reaction on pyridines prompted us to examine its use in the synthesis of substituted thiazoies. 

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