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Peri‐ and Enantioselectivity of Thermal, Scandium‐, and [Pybox/Scandium]‐Catalyzed Diels–Alder and Hetero‐Diels–Alder Reactions of Methyl ( E )‐2‐Oxo‐4‐aryl‐butenoates with Cyclopentadiene
Author(s) -
Desimoni Giovanni,
Faita Giuseppe,
Toscanini Marco,
Boiocchi Massimo
Publication year - 2007
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.200700995
Subject(s) - chemistry , trifluoromethanesulfonate , scandium , cyclopentadiene , absolute configuration , cycloaddition , stereospecificity , medicinal chemistry , enantiomeric excess , aryl , stereochemistry , catalysis , organic chemistry , enantioselective synthesis , alkyl
The cycloaddition between methyl ( E )‐2‐oxo‐4‐aryl‐3‐butenoates ( 2 a – d ) and cyclopentadiene, in addition to the expected normal Diels–Alder (DA) adducts endo‐ 3 a – d and exo‐ 4 a – d , gives the less expected endo ‐ 5 a – d products of the [4+2] hetero‐Diels–Alder (HDA) reaction in which the α‐ketoester behaves as a heterodiene. If a comparison is made between the thermal and the scandium(III) triflate‐catalyzed conditions, the periselectivity changes and whereas under thermal conditions the main products are those from the DA reaction ( 3 a – d ), in the presence of Sc(OTf) 3 (OTf=triflate), the HDA products 5 a – d become largely predominant. The reactions are enantioselectively catalyzed by the scandium(III) triflate complex of (4′ S, 5′ S )‐2,6‐bis[4′‐(triisopropylsilyl)oxymethyl‐5′‐phenyl‐1′,3′‐oxazolin‐2′‐yl]pyridine ( 1 ) and both the DA and the HDA products are obtained with excellent enantiomeric excess, up to >99 % ee . The X‐ray crystallographic structure determination of 5 c assigns it the 4 R, 4a S, 7a R absolute configuration. The thermal retro‐Claisen rearrangement of 3 c into (4 R, 4a S, 7a R )‐ 5 c allows the correlation of their absolute configuration, and 3 c has therefore the 2 R ,3 R configuration. By analogy the same absolute configuration can be assigned to 3 a , b , d and 5 a , b , d , and the stereospecific thermal Claisen rearrangement of the optically active 5 a , b , d into 3 a , b , d completes the correlation between their absolute configuration. The [3,3]‐sigmatropic rearrangements can be easily carried out under catalytic conditions with scandium(III) triflate, which promotes the equilibration between 3 a – d and 5 a – d , with a different degree of enantioselectivity characterizing the process starting from 3 a – d or 5 a – d . The unambiguous attributions of the configuration to the products allows us to propose a rationale of the stereochemical outcome of the catalyzed cycloaddition and to investigate the reaction mechanism of the competing DA and HDA reactions and shifts in products distribution by acid catalysis.