Monensin Claisen rearrangement

Excellent experimental technique was required to effect formation of the monensin cA> ring system (218) via silyl ester enolate Claisen rearrangement of acid (216) and alcohol (217) (Scheme 42). Ester... 

This result in particular should warn you that the choice between a chair- and boat-like transition state is narrow. In general open-chain compounds prefer the chair and cyclic compounds the boat but do not rely on it In spite of this apparent disadvantage the Ireland version of the Claisen rearrangement is one of the most widely used ways to set up complicated molecules. Ireland himself has used it to make a catalogue of polyether antibiotics with the monensin synthesis being perhaps the most remarkable. These syntheses are beyond the scope of this book but are worth reading.36... 

The most complex application of the Ireland-Claisen rearrangement is Ireland s synthesis of monensin A (Fig. 4.2). Claisen rearrangements were ultimately used to establish the C4-C5, C12-C13, and C16-C17 bonds. 

In a program aimed at the total synthesis of polyether antibiotic monensin, Ireland et al. devised a procedure for the in situ silylation of an ester enolate with a j5-leaving group, first executed with the model substrate 165 (Scheme 32). When added to a premixed solution of LDA and TMSCl in 10% HMPA/THF at -100°C, crotyl ester 165 produced after rearrangement at room temperature, desilylation, and treatment with diazomethane, the diastereomeric Claisen products 166 a and 166 b in almost 80% combined yield [63]. The success of this three-component competition experiment depended on the relative rates of N-silylation vs. enolization and -elimination vs. 0-silylation, respectively, with all of these processes occurring on a subminute time scale at -100 C. 

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