Halogen dance reactions--a review.

Halogen Dance (HD) reactions are a useful tool for synthetic chemists as they enable access to positions in aromatic and heteroaromatic systems for subsequent functionalization which are often difficult to address by other methods, hence, allowing entry to versatile scaffolds. While the method can be extremely useful, this transformation is often neglected upon designing synthetic sequences. This may be largely attributed to the lack of comprehensive reference works covering the general principles and outlining the versatility and limitations of the technique. The following review tries to present HD reactions in a clear and concise manner in order to convince more chemists of its advantages. It covers the field of HD reactions from their first observation in 1951 until the present. The important contributions leading to the elucidation of the mechanism are briefly outlined followed by a detailed mechanistic section and a discussion of factors which influence HD reactions. Finally, an overview of HD reactions on various carbocyclic and heterocyclic ring systems and its applications in the synthesis of complex compounds is given.

Halogenated 2'-chlorobithiazoles via Pd-catalyzed cross-coupling reactions.

Halogenated bithiazoles allow facile further functionalization and are, therefore, suitable intermediates for the synthesis of compounds with interesting biological activity or material science properties. The applicability of three coupling methods (Negishi, Suzuki, and Stille) for the synthesis of the title compounds was compared. The Negishi method proved to be troublesome, and side reactions were predominant. The synthesis of the first thiazoleboronic acid ester offered a new method for the formation of bithiazoles, not generally applicable so far. The lower toxicity compared to that of tin organyls make this method an approach with interesting perspectives. The Stille coupling proved to be superior to the other methods and enabled the synthesis of the title compounds with diverse connectivity.

Synthesis of novel sterically demanding carbo- and heterocyclic beta-ketoesters.

We present an easy method for the synthesis of beta-ketoesters starting from various carbocyclic and heterocyclic carboxylic acids and esters. The beta-ketoester side-chain was introduced by a sequence involving alpha-deprotonation and quenching with CO(2), conversion to the corresponding acid chloride and subsequent chain elongation using deprotonated ethyl acetate.

Novel and efficient access to phenylamino-pyrimidine type protein kinase C inhibitors utilizing a Negishi cross-coupling strategy.

A novel, short, and efficient synthetic pathway to 3-{4-[2-(3-chlorophenylamino)-pyrimidin-4-yl]-pyridin-2-ylamino}-propanol (CGP 60474) and a series of analogues was developed. The synthetic sequence consisted of a Negishi-type cross-coupling reaction in the key step followed by two subsequent nucleophilic substitution reactions. This strategy represents a versatile and robust protocol to access diverse analogues of the title compound for subsequent SAR studies as potential phenylamino-pyrimidine type protein kinase C inhibitors.

Investigations of the halogen dance reaction on N-substituted 2-thiazolamines.

The halogen dance (HD) reaction on various 2-thiazolamine systems was investigated providing an easy access to a series of 5-substituted 4-bromo-2-thiazolamine derivatives. We could show that HD is a very favored process for the investigated systems and that prevention of HD is only possible when optimized reaction conditions and selected electrophiles are applied.

Synthesis of pyrrolo[2,3-d][1,2,3]thiadiazole-6-carboxylates via the Hurd-Mori reaction. Investigating the effect of the N-protecting group on the cyclization.

A route to methyl pyrrolo[2,3-d][1,2,3]thiadiazole-6-carboxylates as potential plant activators and inducers of systemic acquired resistance (SAR) is reported. A synthetic strategy based on cyclization of the thiadiazole ring system utilizing thionyl chloride via the Hurd-Mori protocol as key step was developed. Success of the ring closure reaction turned out to be highly dependent on the nature of the N-protecting group of the pyrrolidine precursor. While electron donors such as alkyl gave only poor conversion to the required 1,2,3-thiadiazoles, an electron withdrawing substituent such as methyl carbamate gave superior yields.

First enantiodivergent Baeyer-Villiger oxidation by recombinant whole-cells expressing two monooxygenases from Brevibacterium.

Microbial Baeyer-Villiger oxidations of representative mesomeric ketones with recombinant Escherichia coli cells expressing two monooxygenases from Brevibacterium were investigated. The two enzymes displayed enantiodivergent biotransformations on an array of structurally diverse substrates, allowing access to some key lactone intermediates in natural compound synthesis.