The first practical, yet simple, preparation of aryl(alkynyl)iodonium trifluoroacetate salts is described. The generic nature of this synthetic method has allowed the production of a range of aryl(alkynyl)iodonium trifluoroacetate salts with independent variation of both the alkynyl and aryliodo groups in yields of 30–85 %. Application of these new reagents to the synthesis of a series of 2‐arylfuro[3,2‐c]pyridines (40–64 %) highlights the potential of this class of materials as precursors to bioactive heterocyclic structures. These experiments have also demonstrated that, in this case, the effect of the aryliodo group on the reaction is negligible.
Aryl(alkynyl)iodonium salts have been demonstrated to be valuable precursors to a diverse range of heteroaromatic ring systems including aryl[1,2-a]imidazopyridines. Successful application, using the recently described aryl(alkynyl)iodonium trifluoroacetate salts, is described, highlighting for the first time that the regioselectivity of this process is both counter-ion and concentration dependent. Studies with a carbon-13 labelled substrate established that the reactions of alkynyliodonium salts are highly complex and that multiple mechanistic processes appear to be underway simultaneously.
Two approaches to the synthesis of compounds corresponding to the C17-C27 fragment of the 20-deoxybryostatins are described. The first approach is based on the palladium(0) catalysed coupling of tin enolates, generated in situ from enol acetates using tributyltin methoxide, with vinylic bromides. The vinylic bromides were prepared using the Sharpless asymmetric dihydroxylation to introduce the hydroxyl groups corresponding to those at C25 and C26 in the bryostatins. Following several steps to introduce alkynyl ester functionality, the stereoselective addition of a tributyltin cuprate followed by tributyltin-bromine exchange gave the required vinylic bromides. The palladium(0) catalysed couplings worked very well for enol esters containing thioether substituents and gave products with retention of the position and geometry of the trisubstituted double bond derived from the vinylic bromide. These were taken through to compounds corresponding to fully developed C17-C27 fragments ready for assembly of the 16,17-double-bond of bryostatins by Julia reactions. This chemistry was also applied to prepare intermediates suitable for incorporation into bryostatins by ring-closing metathesis but, in this case, the coupling reaction gave mixtures of products including both the required βγ-unsaturated ketone and a conjugated diene formed by a competing Heck reaction. To avoid this problem, a second approach to compounds suitable for incorporation into a metathesis-based assembly of 20-deoxybryostatins was developed. In this organotin-free synthesis, the key step was the conjugate addition of an organic cuprate generated from allylmagnesium bromide to an alkynoate that gave the required (Z)-trisubstituted alkene with excellent stereoselectivity. This was converted into metathesis precursors in a few steps.
A variety of methods for the preparation of selectively mono-, di-or tri-labelled arenes are reviewed. The review concentrates on those for which the application to labelled synthesis has been demonstrated. Further methods, the application of which to labelled synthesis appears viable but which have not been reduced to practise, are included also. The available methods provide a range of substitution patterns.
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