Decalin Claisen rearrangements

Thermal aza-Claisen rearrangements were induced upon heating the reactant 99 in decalin to 135-190 °C. Though some product 100 could be obtained. 

In a series of elegant studies, Paquette and coworkers demonstrated the potential of the Claisen rearrangement for the stereocontrolled total synthesis of natural products. Dehydrative coupling of (2)-3-(trimethylsilyl)-2-propen-l-ol with cyclohexanone (51) under Kuwajima s conditions, followed by rearrangement of enol ether (52) in decalin, led in excellent stereoselectivity (>99 1) to aldehyde (53 Scheme 8). Concise construction of the eight-membered core of acetoxycrenulidine was achieved by intramolecular phenylseleno etherification of lactone (54), introduction of the exocyclic vinyl ether double bond by selenoxide elimination and subsequent Claisen rearrangement (Scheme 9, 66% from 54). ... 

A further advantage of the c/s-oriented 4,6 Claisen rearrangement is the stereospecific alkylation of decalin and hydrindane systems4 9 420. Further examples are reported in refs 167. 240 and 421-425. 

In the synthesis in Scheme 13.34, the first configuration that is established after construction of the decalin system is the one at C-8 in step A. An enolate alkylation is carried out with methallyl iodide. The observed, and desired, stereochemistry is governed by the C-10 methyl group, which blocks attack from the top side of the molecule. In step B, the five-membered ring is formed by intramolecular aldol condensation. The reduction of the enone (step C) establishes the configuration at C-13, and this chirality is subsequently transferred to C-9 by the intramolecular Claisen rearrangement in step D. 

The repetitive Claisen Cope rearrangement can be used as a strategy for the iterative introduction of ( )-isoprene units into a growing chain. Thus, reduction of intermediate aldehyde 44 (see above) to the corresponding alcohol 46 and treatment with acetal 40 affords a 1 1 mixture of the Claisen product 47 and Claisen-Cope product 48 in 30% yield. The tandem Claisen-Cope-Cope product 49 is obtained by heating 48 in decalin to 190°C. 

A computational and experimental study of the oxy-Cope rearrangement of aldol products has been reported (Scheme 22) and a diastereoselective oxy-Cope/ene/Claisen reaction for the synthesis of decalin frameworks possessing four contiguous stereogenic centres has been applied. The aza-Cope/Mannich reaction has been reviewed. ... 

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