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Tosylhydrazide‐Promoted Diastereoselective Intramolecular 1,3‐Dipolar Cycloadditions: Synthesis of Tetrahydropyrrolo[3,4‐ c ]pyrazoles
Author(s) -
Barroso Raquel,
Escribano Maria,
Cabal MariaPaz,
Valdés Carlos
Publication year - 2014
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.201301587
Subject(s) - chemistry , intramolecular force , cycloaddition , diazo , stereoselectivity , hydrazone , ketone , bicyclic molecule , stereochemistry , enantiomer , combinatorial chemistry , medicinal chemistry , organic chemistry , catalysis
A very straightforward diastereoselective synthesis of tetrahydropyrrolo[3,4‐ c ]pyrazoles by intramolecular 1,3‐dipolar cycloaddition is described. The starting materials for the synthetic route are N ‐Boc‐protected α‐amino acids, which are first transformed into N ‐allyl‐α‐amino ketones through conventional methodologies. Then, a one‐pot sequence that involves formation of a tosylhydrazone from the ketone, base‐induced decomposition of the hydrazone, and intramolecular 1,3‐dipolar cycloaddition of the diazo compound generated, gives rise to the bicyclic systems with total diastereoselectivity and high preservation of the enantiomeric purity. However, the analogous process employing α‐amino aldehydes lacks stereoselectivity. DFT computational modeling has been carried out to account for the different behavior of the two types of systems.