Cascade Radical Carbonylations Leading to 3-Substituted Cyclohexanones

Abstract

Tin radical mediated [5+1]-annulation methods leading to 3-substituted cyclohexanones were investigated. Cyclohexanones having a quaternary center at the 3-position were synthesized in good yields by allyltin-mediated three- and four-component cascade reactions that involve (i) radical carbonylation, (ii) 6-endo cyclization, and (iii) alkene addition.

tributyltin radical - allyltributyltin - radical cyclization - casacde reaction - carbon monoxide

References and Notes

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<A NAME="RY00606ST-3">3</A>

For a 6-endo reaction using a Zn-induced system, see ref. 1h.

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<A NAME="RY00606ST-6">6</A>

The reaction also gave the product via a 5-exo/allylation sequence in 5% yield. At higher CO pressures, the second carbonylation of the 5-exo-radical also took place. Details will be discussed in a full paper.

<A NAME="RY00606ST-7">7</A>

3-Allyl-3-methylcyclohexanone ( 2d)
A magnetic stirring bar, AIBN (26.2 mg, 0.16 mmol), benzene (3.4 mL), 4-methyl-4-pentenyl bromide (1d; 92.3 mg, 0.56 mmol), and allyltributyltin (400.0 mg, 1.2 mmol) were placed in a 50-mL stainless-steel autoclave. The autoclave was closed, purged three times with CO, pressurized with 50 atm of CO, and then heated at 80 °C for 12 h. Excess CO was discharged at r.t. The solvent was removed under reduced pressure. The residue was purified by flash chromatography on silica gel (hexane→hexane-EtOAc, 10:1) to give 3-allyl-3-methylcyclohexanone (2d; 73.3 mg, 85%).