637033-15-9

Upstream product

• 22082-43-5 2-hydroxy-2-methyl-pent-4-en-3-one 
• 78-79-5 isoprene 
• 22141-88-4 3-methoxy-2-methyl-penta-3,4-dien-2-ol 

Downstream Products

• 6090-09-1 methyl-[(1S)-4-methylcyclohex-3-enyl]ketone 

Relevant academic research and scientific papers

(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.

α′-hydroxy Enones as Achiral Templates for Lewis Acid-Catalyzed Enantioselective Diels - Alder Reactions

α′-Hydroxy enones react with dienes in the presence of (S,S)-[Cu(tBu-box)](OTf)2 or (S,S)-[Cu(tBu-box)](SbF6)2 (2 to 10 mol %) to afford the corresponding Diels?Alder adducts in high yield and selectivity. Isomeric ratios (regioselectivity, endo/exo or cis/trans) of up to >99:1 and ee values of up to >99% are obtained. Significantly, difficult dienes such as isoprene, 2,3-dimethyl butadiene and piperylene behave satisfactorily. Subsequent oxidative cleavage of the ketol in the resulting cycloadducts by treatment with cerium ammonium nitrate (CAN) yields the corresponding enantiopure carboxylic acids. Alternatively, carbonyl addition and subsequent diol cleavage with CAN produces the corresponding ketone adducts. Copyright