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Highly Diastereoselective Samarium Diiodide Induced Ketyl Cyclisations of Indole and Pyrrole Derivatives – Scope and Limitations
Author(s) -
Beemelmanns Christine,
Blot Virginie,
Gross Steffen,
Lentz Dieter,
Reissig HansUlrich
Publication year - 2010
Publication title -
european journal of organic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.825
H-Index - 155
eISSN - 1099-0690
pISSN - 1434-193X
DOI - 10.1002/ejoc.200901455
Subject(s) - chemistry , pyrrole , diastereomer , indole test , ketyl , alkylation , samarium , stereocenter , stereochemistry , medicinal chemistry , combinatorial chemistry , organic chemistry , enantioselective synthesis , radical , catalysis
Here we summarise our results for SmI 2 ‐induced 5‐ exo ‐ trig to 8‐ exo ‐ trig reductive cyclisations of suitably substituted indole and pyrrole derivatives. All precursors were easily prepared by simple N ‐alkylation or N ‐acylation of indole and pyrrole derivatives with the corresponding iodo alkanones, acid chlorides or lactones. The SmI 2 ‐induced cyclisations in most cases provided tri‐ and tetracyclic derivatives, even in the absence of HMPA, in good to very good yields and with excellent diastereoselectivities. Extensive investigations of the reaction conditions revealed that in the presence of different proton sources SmI 2 ‐induced cyclisations afforded mainly one major type of diastereomer (thermodynamic control), so the formation of three or four stereogenic centres is controlled in one step. The mechanism of the SmI 2 ‐induced ketyl coupling is discussed in more detail on the basis of these observations and two possible mechanistic pathways are compared. The assumed intermediate samarium enolates were also trapped with allyl iodide, furnishing interesting polycyclic N‐heterocycles bearing newly formed quaternary centres as single diastereomers.