Synthesis of α,β-disubstituted cycloalkenones through a sequence of olefin metathesis and oxidative rearrangement

Tetrahedron Letters

Volumn 43, Issue 50, 2002, Pages 9035-9038

  Meng, Dongfang ^a   Parker Jr , Dann L ^a  

^a MERCK RESEARCH LABORATORIES   (United States)

Author keywords

Allylic oxidative rearrangement; Cycloalkenones; Olefin metathesis

Indexed keywords

ALKENE; ETHYLENE; KETONE DERIVATIVE;

ARTICLE; CATALYST; DIASTEREOISOMER; DRUG OXIDATION; DRUG SYNTHESIS; NUCLEAR MAGNETIC RESONANCE; POLYMERIZATION; RING CLOSING METATHESIS; RING OPENING;

EID: 0037049194     PISSN: 00404039     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0040-4039(02)02307-9     Document Type: Article

References (15)

1. Published Merck patent application: Parker, D.; Ratcliffe, R.; Wilkening, R.; Wildonger, K. WO 0182923-A1.
2. For a recent method to make β-monosubstituted cycloheptenones, see: Piers E., Walker S.D., Armherst R. J. Chem. Soc., Perkin Trans. 1. 2000;635.
3. Danishefsky, S. J. C & EN 2002, Feb. 11
4. For a thorough list of references about RCM, please see references in: Furstner A., Radkowski K., Wirz C., Goddard R., Lehmann C.W., Mynott R. J. Am. Chem. Soc. 124:2002;7061.
5. Schwab P., France M.B., Ziller J.W., Grubbs R.H. Angew. Chem., Int. Ed. Engl. 34:1995;2039.
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10. All allylic/benzylic tertiary alcohols like 7, 8, 12, and 13 were acid sensitive and used crude. Because of this instability, it was difficult to follow RCM and AOR reactions by TLC or LCMS.
11. Dolman S.J., Sattely E.S., Hoveyda A.H., Schrock R.R. J. Am. Chem. Soc. 124:2002;6991.
12. Professor Hoveyda and colleagues have reported using ethylene to mediate ring opening-ring closing metathesis in the synthesis of chromenes. Thermodynamically more stable cyclostyrenes (chromenes) were made from diene substrates containing one styrene and one cycloalkene (in one case, one styrene and two monosubstituted alkenes). The major function of ethylene in their case was to prevent oligomerization under relatively high substrate concentration (usually 0.1 M). In our system to make substituted cycloalkenes from trienes, oligomerization was not a problem at low concentration (0.005 M), even without ethylene. By contrast, at 0.1 M reactions were messier (oligomerization?) regardless of the presence or absence of ethylene. (a) Harrity, J. P. A.; La, D. S.; Cefalo, D. R.; Visser, M. S.; Hoveyda, A. H. J. Am. Chem. Soc. 1998, 120, 2343; (b) Harrity, J. P. A.; Visser, M. S.; Gleason, J. D.; Hoveyda, A. H. J. Am. Chem. Soc. 1997, 119, 1488.
13. Professor Hoveyda and colleagues have reported using ethylene to mediate ring opening-ring closing metathesis in the synthesis of chromenes. Thermodynamically more stable cyclostyrenes (chromenes) were made from diene substrates containing one styrene and one cycloalkene (in one case, one styrene and two monosubstituted alkenes). The major function of ethylene in their case was to prevent oligomerization under relatively high substrate concentration (usually 0.1 M). In our system to make substituted cycloalkenes from trienes, oligomerization was not a problem at low concentration (0.005 M), even without ethylene. By contrast, at 0.1 M reactions were messier (oligomerization?) regardless of the presence or absence of ethylene. (a) Harrity, J. P. A.; La, D. S.; Cefalo, D. R.; Visser, M. S.; Hoveyda, A. H. J. Am. Chem. Soc. 1998, 120, 2343; (b) Harrity, J. P. A.; Visser, M. S.; Gleason, J. D.; Hoveyda, A. H. J. Am. Chem. Soc. 1997, 119, 1488.
14. Ratcliffe R., Rodehorst R. J. Org. Chem. 35:1970;4000.
15. 2 (0.005 M) was stirred at 40°C for 2-3 h, then cooled to room temperature and treated with PDC (2 equiv., 40°C) or freshly prepared Ratcliffe reagent (18 equiv., rt). After 1 h, the reaction was worked up and purified as above. Overall yields of 14a-c from 10 were ∼20%.