Catalytic highly enantioselective vinylogous Povarov reaction

Abstract

The first example of a catalytic asymmetric vinylogous Povarov reaction is presented. 1-N-Acylamino-1,3-butadienes react selectively at their terminal double bond in the presence of a chiral phosphoric acid catalyst, delivering highly enantioenriched 1,2,3,4-tetrahydroquinolines bearing a synthetically versatile enecarbamate group at the 4-position.

Evolution of a Multicomponent System: Computational and Mechanistic Studies on the Chemo‐ and Stereoselectivity of a Divergent Process

“…Interestingly, 5 did not evolve to 4 b under reaction conditions nor with BF 3 ⋅ Et 2 O treatment 12. The outcome of this reaction exemplifies the distinct products that can be obtained from the interaction of dienes and imines (whether they are generated in situ or not), leading to either Povarov or imino‐DA adducts 13…”

“…The role of this crucial species is to increase the reactivity of the imine by coordination of the nitrogen atom with the Lewis or Brønsted acid, thus leading to a more electrophilic species towards nucleophilic additions or to more reactive dienophiles that have lower LUMOs. Apart from Sc(OTf) 3 , an usual Lewis acid for the Povarov and other imine‐based MCRs (Table 1, entry 1),13 BF 3 ⋅ Et 2 O was also efficient, yielding a similar ratio of products 4 b / 5 although in a slightly increased overall yield under the usual conditions (RT, 20 % of the catalyst, entry 2). Similar findings were obtained when camphorsulfonic acid (CSA) was utilized (entry 3).…”

“…[12] The outcome of this reaction exemplifies the distinct products that can be obtained from the interaction of dienes and imines (whether they are generated in situ or not), leading to either Povarov or imino-DA adducts. [13] The structural elucidation of the obtained compounds was performed in a standard manner with spectroscopical methods ( 1 H and 13 C, COSY, HMBS, HSQC and NOESY NMR experiments) and with the aid of geometry optimization studies (MM94F, AM1 and B3LYP density functional calculations in a Spartan suite). The stereochemistries assigned for the two compounds ( Figure 1) are in agreement with the observed trends for the previously reported results on this MCR.…”

An Atropisomerically Enforced Phosphoric Acid for Organocatalytic Asymmetric Reactions

“…We then moved to study the related vinylogous Povarov reaction of the same aldimine 7 with 1‐amidodiene 10 (Table ) . According to our previous studies, this reaction is somehow complementary to the previous one in terms of catalyst requirements; catalyst 2 gives good enantioselectivity, whereas both the more hindered phosphoric acid 1 and the less substituted 3 afford very poor results (entries 1–3).…”

“…Benzyl {( E )‐2‐[(2 S ,4 R )‐6‐Methoxy‐2‐phenyl‐1,2,3,4‐tetrahydroquinolin‐4‐yl]vinyl}carbamate (11): To a flame‐dried Schlenk tube equipped with a magnetic stirring bar, 4 Å powdered molecular sieves (ca. 20 mg) were added under a N 2 atmosphere.…”