Development of an α′-hydroxy enone for the aminocatalytic asymmetric formal conjugate addition of aldehydes to acrylates, vinyl ketones and acrolein

Aminocatalytic asymmetric conjugate addition of aldehydes to Michael acceptors is a well established C-C bond forming methodology. However, various acrylic-type acceptors, including acrylic acid derivatives and acrolein, remain reluctant. Here we demonstrate that the internal H-bonding self-activation in α'-hydroxy enones allows them to react smoothly with enolizable aldehydes using commercially available aminocatalysts to afford adducts in good yields and high enantioselectivity. Straightforward conversion of the ketol moiety of these adducts into aldehyde, ketone and carboxylic acid functionalities offers an indirect, unified entry to products derived from acrolein, alkyl-vinyl ketones and acrylates, respectively.Support has been provided by the Basque Government (GV grant IT‐1583‐22), and Ministerio de Ciencia e Innovación (grant PID2019‐109633GB/AEI/10.13039/501100011033), Spain. A predoctoral grant to B. L. from Navarra Government is acknowledged

Asymmetric propionate aldol reactions of a chiral lithium enolate accessible from direct enolization with n-butyllithium

The presented lithium enolate-based methodology is suitable for access to propionate syn-aldol motifs with high levels of stereocontrol. The reactive lithium enolate species is generated by direct treatment of a camphor-based chiral ethyl ketone with butyllithium, and is subsequently submitted to aldolization with a broad variety of aldehydes. The product aldols are obtained in uniformly high yields and high d.r. values (ranging from 91:9 to >98:2) irrespective of the aliphatic (both linear and branched chain), α,β-unsaturated, aromatic, or hetero-aromatic nature of the aldehyde employed. The crystallinity of most of the obtained adducts offers an easy access to almost 100% isomerically pure products upon a single recrystallisation. The auxiliary (1R)- (+)-camphor can be removed easily from the adducts for reuse, thereby producing the corresponding syn propionate aldols. This technology is implemented in the synthesis of a key subunit of the multi-drug resistance reversing agent hapalosin.This work was finantially supported by the Universidad del País Vasco, Gobierno Vasco, and by MEC. Grants to M. C. G.-R. from Gobierno Vasco and to P. B. from MEC are acknowledged

Catalytic Asymmetric Synthesis of Quaternary Barbituric Acids

The catalytic asymmetric α-functionalization of prochiral barbituric acids, a subtype of pseudosymmetric 1,3-diamides, to yield the corresponding 5,5-disubstituted (quaternary) derivatives remains essentially unsolved. In this study 2-alkylthio-4,6-dioxopirimidines are designed as key 1,3-diamide surrogates that perform exceedingly in amine-squaramide catalyzed C–C bond forming reactions with vinyl ketones or Morita–Baylis–Hillmann-type allyl bromides as electrophiles. Mild acid hydrolysis of adducts affords barbituric acid derivatives with an in-ring quaternary carbon in unprecedented enantioselectivity, offering valuable materials for biological evaluations

N-(Diazoacetyl)oxazolidin-2-thiones as Sulfur-Donor Reagents: Asymmetric Synthesis of Thiiranes from Aldehydes

ISSN: 1433-7851 (print) 1521-3773 (web)We reported the first Rh-catalyzed reaction of a diazoacetyl compound with aldehydes that affords thiiranes, instead of oxiranes, as known before. This unusual reactivity relied on the use of N-(diazoacetyl)oxazolidin-2-thiones as new chiral sulfur-donor reagents and enabled the direct production of optically active thiiranes with very high stereoselectivity.Depto. de Química InorgánicaFac. de Ciencias QuímicasTRUEpu