1210897-85-0

Upstream product

• 14371-10-9 (E)-3-phenylpropenal 
• 1165952-91-9 cyclohexa-1,3-diene 

Relevant academic research and scientific papers

The development of highly active acyclic chiral hydrazides for asymmetric iminium ion organocatalysis

Double asymmetric induction has been employed as a tool to optimise pyrazolidinone-derived organocatalysts for the asymmetric iminium ion catalysed Diels-Alder reaction. Mechanistic studies revealed a superior hydrazide catalyst deriving from methanolysis of the chiral pyrazolidinone precursor. This catalyst displays unusually high endo diastereoselectivity and good enantioselectivity with a range of β-arylenals and cyclic dienes at catalyst loadings as low as 1 mol%.

(1R)-(+)-camphor and acetone derived α′-hydroxy enones in asymmetric diels-alder reaction: Catalytic activation by Lewis and bronsted acids, substrate scope, applications in syntheses, and mechanistic studies

Chemical Equation Presented The Diels-Alder reaction constitutes one of the most powerful and convergent C-C bond-forming transformations and continues to be the privileged route to access cyclohexene substructures, which are widespread within natural products and bioactive constituents. Over the recent years, asymmetric catalytic Diels-Alder methodologies have experienced a tremendous advance, but still inherently difficult diene-dienophile combinations prevail, such as those involving dienes less reactive than cyclopentadiene or dienophiles like β-substituted acrylates and equivalents. Here the main features of a'-hydroxy enones as reaction partners of the Diels-Alder reaction are shown, with especial focus on their potentials and limitations in solving the above difficult cases. α'-Hydroxy enones are able to bind reversibly to both Lewis acids and Bronsted acids, forming 1,4-coordinated species that are shown to efficiently engage in these inherently difficult Diels-Alder reactions. On these bases, a convenient control of the reaction stereocontrol can be achieved using a camphor-derived chiral α'-hydroxy enone model (substrate-controlled asymmetric induction) and either Lewis acid or Bronsted acid catalysis. Complementing this approach, highly enantio- and diastereoselective Diels-Alder reactions can also be carried out by using simple achiral α'-hydroxy enones in combination with Evans' chiral Cu(II)BOX complexes (catalyst-controlled asymmetric induction). Of importance, α'-hydroxy enones showed improved reactivity profiles and levels of stereoselectivity (endo/exo and facial selectivity) as compared with other prototypical dienophiles in the reactions involving dienes less reactive than cyclopentadiene. A rationale of some of these results is provided based on both kinetic experiments and quantum calculations. Thus, kinetic measurements of Bronsted acid promoted Diels-Alder reactions of α'-hydroxy enones show a first-order rate with respect to both enone and Bronsted acid promoter. Quantum calculations also support this trend and provide a rational explanation of the observed stereochemical outcome of the reactions. Finally, these fundamental studies are complemented with applications in natural products synthesis. More specifically, a nonracemic synthesis of (-)-nicolaioidesin C is described wherein a Brαnsted acid catalyzed Diels-Alder reaction involving a α'-hydroxy enone substrate is the key step toward the hitherto challenging tri substituted cyclohexene subunit.