Multiple Carbon Bond Formation Via the Radical Cyclization of Cycloalkenol Acetals. Application to trans Hydrindan Steroid Precursors

Abstract

The cyclization of the α-iodo mixed acetals derived from properly substituted cyclohexenols , a process which has already been shown to permit the stereoselective and regioselective introduction of a different carbon chain at each of the termini of the allylic double bond, may be used for the construction of trans hydrindans suitable for further elaboration to steroids. In one particular instance, the process involves the formation of four new carbon-carbon bonds in a single operation.

Synthesis of DOHNAA, a Mycobacterium tuberculosis Cholesterol CD Ring Catabolite and FadD3 Substrate

“…Comparison to the literature data was somewhat complicated. There are only three reported NMR spectra in the literature for DOHNNA – one of which is for the racemic compound and incomplete;14 of the other two,12,35 only one gives both 1 H and 13 C data. In addition, the two reported proton spectra do not agree very well with one another, differ in their assignment of signals to the structure, and report the signals as multiplets centred about a single signal rather than as a range.…”

“…We set out to design a synthetic route towards catabolite 2 that would also allow for the facile synthesis of derivatives with which to probe its role as a ligand of KstR2 and FadD3. While a synthesis of 2 has been reported previously, the route to 2 was long and unsuitable to support SAR studies 14…”

Radical Cyclization of Haloacetals: The Ueno-Stork Reaction

“…Stork reported an attempt to run a more complex cascade reaction involving an annulation process via intermolecular addition to acrylamide of the radical obtained from the initial iodoacetal cyclization. 213 The desired product was, however, obtained only in moderate yield, since further reaction of the final radical with acrylonitrile could not be avoided.…”