Forskolin Editing via Radical Iodo- and Hydroalkylation

Synthesis ◽  
2021 ◽  
Author(s):  
Elena Pruteanu ◽  
Nicholas D. C. Tappin ◽  
Veaceslav Kulciţki ◽  
Philippe Renaud ◽  
Vladilena Gîrbu ◽  
...  
Keyword(s):  
Iodine Atom ◽  
Cyclic Ether ◽  
Radical Addition ◽  
Chain Process ◽  
Radical Chain ◽  
Radical Process ◽  
Atom Transfer Radical Addition ◽  
Carbon Centered Radical ◽  
Radical Chain Process

AbstractThe modification of highly oxygenated forskolin as well as manoyl and epi-manoyl oxide, two less functionalized model substrates sharing the same polycyclic skeleton, via intermolecular carbon-centered radical addition to the vinyl moiety has been investigated. Highly regio- and reasonably stereoselective iodine atom transfer radical addition (ATRA) reactions were developed. Unprotected forskolin afforded an unexpected cyclic ether derivative. Protection of the 1,3-diol as an acetonide led the formation of the iodine ATRA product. Interestingly, by changing the mode of initiation of the radical process, in situ protection of the forskolin 1,3-diol moiety as a cyclic boronic ester took place during the iodine ATRA process without disruption of the radical chain process. This very mild radical-mediated in situ protection of 1,3-diol is expected to be of interest for a broad range of radical and non-radical transformations. Finally, by using our recently developed tert-butyl­catechol-mediated hydroalkylation procedure, highly efficient preparation of forskolin derivatives bearing an extra ester or sulfone group was achieved.

A kinetic study of the reaction of adamantanethione with 2-adamantanethiol

1976 ◽  
Vol 54 (21) ◽  
pp. 3407-3411 ◽  
Author(s):  
J. C. Scaiano ◽  
J. P.-A. Tremblay ◽  
K. U. Ingold
Keyword(s):  
Benzene Solution ◽  
Hydrogen Abstraction ◽  
Chain Process ◽  
Radical Chain ◽  
Diffusion Controlled ◽  
Carbon Centered Radical ◽  
Photochemical Initiation ◽  
Kinetics Of ◽  
Radical Chain Process ◽  
Termination Process

The title reaction is a free radical chain process which yields di(2-adamantyl)disulfide(2). The kinetics of this reaction have been studied in benzene solution at 50 °C using both thermal and photochemical initiation. Thermal initiators which yield resonance stabilized carbon-centered radicals were surprisingly inefficient at starting the reaction. The kinetics indicate that the rate controlling propagation step is hydrogen abstraction from the thiol, AdHSH, by the carbon-centered radical, AdHSSAd•. Rotating sector studies gave a rate constant for this step, k2 = 4 × 104 M−1 s−1. There is some kinetically first order chain termination, but the predominant termination process involves the diffusion-controlled bimolecular self-reactions of AdHSSAd• radicals, 2kt = 1.8 × 1010 M−1 s−1.

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