Rapid assembly of substituted dihydrocyclohepta[3,4]pyrrolo[1,2- a]indoles via a novel, carbene-based, rearrangement reaction [1]

Journal of the American Chemical Society

Volumn 122, Issue 6, 2000, Pages 1215-1216

  Frey, Lisa F ^b   Tillyer, Richard D ^b   Quellet, Stephane G ^a,b   Reamer, Robert A ^b   Grabowski, Edward J J ^b   Reider, Paul J ^b  

^a UNIVERSITY OF TORONTO   (Canada)

^b MERCK RESEARCH LABORATORIES   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

CARBENE; PYRROLE DERIVATIVE;

CHEMICAL REACTION; CHEMICAL REACTION KINETICS; CHEMICAL STRUCTURE; CONTROLLED STUDY; LETTER; REACTION ANALYSIS; SYNTHESIS;

EID: 0034673305     PISSN: 00027863     EISSN: None     Source Type: Journal    
DOI: 10.1021/ja992911i     Document Type: Letter

References (21)

1. De Clercq, E. J. Med. Chem. 1994, 38, 2491.
2. Tan, L.; Chen, C.; Tillyer, R. D.; Grabowski, E. J. J.; Reider, P. J. Angew. Chem., Int. Ed. 1999, 38, 711-713 and references cited therein.
3. (a) This rearrangement was independently observed by Dr. Lilian Radesca, DuPont Pharmaceuticals (personal communication). (b) See Supporting Information for NMR and X-ray data (Figure 1).
4. 9
5. No difference in rate is observed in the presence of base (triethylamine or imidazole), or using acetate prepared in situ.
6. 1/2 = 267 min, all at 75°C.
7. See Supporting Information.
8. Eisch, J. J.; Gadek, F. J. J. Org. Chem. 1971, 36 (22), 3376-3381.
9. D = 1.7, NH vs ND) on the rate of the rearrangement of 2a to 4a at 75°C suggests that N-H bond fission is a feature of the rate-determining step.
10. We thank the referee for pointing out that a similar process has been reported involving formation of a carbene intermediate from a diradical generated under photolysis conditions. Margaretha, Agosta, and co-workers. Kravitz, J. I.; Margaretha, P.; Agosta, W. C. Tetrahedron Lett. 1991, 32, 31-34. See also: (a) Mukherjee, A. D.; Margaretha, P.; Agosta, W. C. J. Org. Chem. 1996, 61, 3388-3391 .
11. We thank the referee for pointing out that a similar process has been reported involving formation of a carbene intermediate from a diradical generated under photolysis conditions. Margaretha, Agosta, and co-workers. Kravitz, J. I.; Margaretha, P.; Agosta, W. C. Tetrahedron Lett. 1991, 32, 31- 34. See also: (a) Mukherjee, A. D.; Margaretha, P.; Agosta, W. C. J. Org. Chem. 1996, 61, 3388-3391 .
12. (b) Margaretha, P.; Reichow, S.; Agosta, W. C. J. Org. Chem. 1994, 59, 5393-5396.
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20. The cation 12 is formally the product of an intramolecular Friedel-Crafts type alkenylation reaction between a phenyl in the trilyl group and 10.
21. D could be consistent with slow formation of o-quinoiminomethide 12. However, rearrangement of 2a in dimethylacetylene dicarboxylate as solvent provided the rearrangement product 4a and no evidence of a Diels-Alder adduct from reaction with the quinoiminomethide.