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Direct, Asymmetric Synthesis of Carbocycle‐Fused Uracils via [4+2] Cycloadditions: a Noncovalent Organocatalysis Approach
Author(s) -
Marcantonio Enrico,
Curti Claudio,
Battistini Lucia,
Sartori Andrea,
Cardinale Luana,
Pelosi Giorgio,
Zanardi Franca
Publication year - 2021
Publication title -
advanced synthesis and catalysis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.541
H-Index - 155
eISSN - 1615-4169
pISSN - 1615-4150
DOI - 10.1002/adsc.202100082
Subject(s) - chemistry , stereocenter , enantiopure drug , organocatalysis , bifunctional , non covalent interactions , enantioselective synthesis , keto–enol tautomerism , combinatorial chemistry , stereochemistry , catalysis , organic chemistry , molecule , hydrogen bond
Abstract The peculiar versatility of remotely enolizable 6‐methyluracil‐5‐carbaldehydes as useful vinylogous pronucleophiles in direct, asymmetric [4+2] cyclizations with suitable nitroolefins has been demonstrated. Under the strategic exploitation of noncovalent bifunctional organocatalysis, a dearomative remote enolization strategy was implemented, to generate o QDM‐type dienolate intermediates that were efficiently and stereoselectively trapped by either aromatic or aliphatic nitroolefins. A series of functionalized, chiral carbocycle‐fused uracils embedding three contiguous stereocenters were thus collected in one step in good yields, with generally good levels of enantioselectivity, and complete diastereocontrol. Furthermore, the ability to provide enantiopure products via simple one‐cycle recrystallizations and the possibility to further functionalize these scaffolds without losing their chiral integrity were demonstrated.