Electron-rich dienes are extremely valuable instruments in chemists’ hands. The first one was revealed to the scientific community with the seminal work of Danishefsky and co-authors, who synthesized in 1974 trans-1-methoxy-3-trimethylsilyloxy-1,3-butadiene (Danishefsky’s diene). Owing to significance and extraordinary properties it has reached privileged status to gain the popularity among synthetic chemists being able to undergo cycloaddition, precisely Diels-Alder, reactions. This strategy enabled the facile synthesis of either various cyclohexenones or their aza-(-oxa) analogs, which paved the way to number of intricate natural products. The further development of more reactive Rawal’s diene 3 in late 1990^th opened new opportunities in synthesis with the use of hetero-Diels-Alder protocol. However, its wide application is nowadays restricted by commercial unavailability, very short shelf life and the absence of large-scale synthetic protocol. As the result, the synthetic potential of Rawal’s diene is a kind of black box now. To cure such a problem, we started from elaboration of a multigram protocol for the preparation of Rawal’s diene. A series of optimization steps allowed for two-stage synthesis of the target diene 3 in overall yield 57% and over 500 g for one synthetic run. During the development of the methodology, a number of critically important technological aspects concerning isolation and storage of the Raval’s diene were investigated. In particular, it was found out that the diene is stable for months if stored at -10^oC under argon. We also devised a methodology enabling preparation of dihydropyranones 5 and 6 via the oxo-Diels-Alder reaction using the Rawal's diene and various ketones and aldehydes in multi-gram quantities. The subsequent modification of the cycloaddition products was performed as well giving access to spiro-derivatives 7 and alcohols 8.

Evgeniy Zarudnitskii

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