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

1a Ryu I. Kusano K. Hasegawa M. Kambe N. Sonoda N. J. Chem. Soc., Chem. Commun.  1991,  1018 

1b Curran DP. Liu H. J. Am. Chem. Soc.  1991,  113:  2127 

1c Tsunoi S. Ryu I. Yamasaki S. Fukushima H. Tanaka M. Komatsu M. Sonoda N. J. Am. Chem. Soc.  1996,  118:  10670 

1d Ryu I. Nagahara K. Kurihara A. Komatsu M. Sonoda N. J. Organomet. Chem.  1997,  548:  105 

1e Ryu I. Nagahara K. Yamazaki H. Tsunoi S. Sonoda N. Synlett  1994,  643 

1f Tsunoi S. Ryu I. Fukushima H. Tanaka M. Komatsu M. Sonoda N. Synlett  1995,  1249 

1g Curran DP. Sisko J. Balog A. Sonoda N. Nagahara K. Ryu I. J. Chem. Soc., Perkin Trans. 1  1998,  1591 

1h Tsunoi S. Ryu I. Yamazaki S. Tanaka M. Sonoda N. Komatsu M. Chem. Commun.  1997,  1889 

For reviews on radical carbonylations, see:

2a Ryu I. Sonoda N. Angew. Chem., Int. Ed. Engl.  1996,  35:  1050 

2b Ryu I. Sonoda N. Curran DP. Chem. Rev.  1996,  96:  177 

2c Ryu I. Chem. Soc. Rev.  2001,  30:  16 

2d See also a review on acyl radicals: Chatgilialoglu C. Crich D. Komatsu M. Ryu I. Chem. Rev.  1999,  99:  1991 

3

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

4a Ryu I. Yamazaki H. Kusano K. Ogawa A. Sonoda N. J. Am. Chem. Soc.  1991,  113:  8558 

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4d Ryu I. Niguma T. Minakata S. Komatsu M. Luo Z. Curran DP. Tetrahedron Lett.  1999,  40:  2367 

5a Keck GE. Enholm EJ. Yates JB. Wiley MR. Tetrahedron  1985,  41:  4079 

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6

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.

7

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%).