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Site‐Selective Calcium‐Catalyzed/Organocatalyzed Condensation of Propargyl Alcohols Tethered to β‐Keto Esters
Author(s) -
Morcillo Sara P.,
Presset Marc,
Floquet Sébastien,
Coeffard Vincent,
Greck Christine,
Bour Christophe,
Gandon Vincent
Publication year - 2016
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.201600394
Subject(s) - chemistry , regioselectivity , propargyl , aldol condensation , nucleophile , intramolecular force , catalysis , michael reaction , organocatalysis , electrophile , organic chemistry , thiourea , medicinal chemistry , enantioselective synthesis
The intramolecular condensation of β‐keto esters to give propargyl alcohols is described. The substrates have two electrophilic sites and two nucleophilic sites. The site selectivity can be fully controlled. In the presence of a calcium‐based catalyst and under anhydrous conditions, O‐addition products are isolated. On the other hand, traces of water or i PrOH as additive encourage calcium‐catalyzed Meyer–Schuster rearrangements. The resulting enones may be further transformed into endo ‐Michael addition products. The regioselectivity of the attack of the enolate can be changed by using 1‐[3,5‐bis(trifluoromethyl)phenyl]‐3‐[2‐(dimethylamino)cyclohexyl]thiourea (TUC) as organocatalyst, which promotes the formation of aldol‐condensation products of high synthetic interest. DFT calculations rationalize the preference for the aldol condensation when TUC is used instead of the endo ‐Michael addition.