Lewis acids Povarov reaction

A solid-phase Ugi-Reissert reaction on chloroformate resin, has been reported. The product, the ot-carbamoylated isoquinoline 230, is released by oxidative cleavage (Scheme 33a). Interestingly, the enamide moiety in the adduct can be exploited to perform this process in tandem with a Povarov MCR [189, 190]. In this way, by interaction of dihydroisoquinoline 231 with aldehydes, anilines and a suitable Lewis acid catalyst, the polyheterocyclic system 232 was prepared (Scheme 33b). The Zhu group devised an innovative approach for the synthesis of this class of compounds. They employed the heterocyclic amine 233, which was oxidized in situ to the dihydroisoquinoline 234 with IBX, to undergo the classic Ugi reaction. Remarkably, all the components are chemically compatible, allowing the sequence to proceed as a true MCR (Scheme 33c) [191]. 

Zhu demonstrated that arynes (generated from 153 with fluoride) smoothly annulate 2-acyl-substituted tetrahydroisoquinolines in moderate to excellent yields at room temperature. The starting tetrahydroisoquinolines (e.g., 154) were prepared via a Lewis acid-catalyzed, three-component Povarov reaction (9 examples, 21-75% yield) (140L1756). 

The Povarov reaction is the inverse electron-demand aza-Diels-Alder reaction, a [4 + 2] cycloaddition between an A-arylimine (as the diene) and an electron-rich olefin (as the dienophile), which gives tetrahydroquinolines 3 or substituted quinolines 4 as the product. This reaction also called as imino-Diels-Alder reaction, usually catalyzed by Lewis or Bronsted acids. Since the jV-arylimine can be prepared in situ from aniline and aldehyde, thus the Povarov reaction can be performed in a one-pot fashion. ... 

The simplest access to 2,4-a 5 1,2,3,4-tetrahydroquinolines 506 via Povarov reaction is the use of vinyl ethers or vinyl amides 67 under Lewis acid catalysis (Scheme 13.111) [203b, 204, 205]. 

C. D. Smith, J. I. GavrUyuk, A. J. Lough, R. A. Batey, J. Org. Chem. 2010, 75, 702—715. Lewis acid catalyzed three-component hetero-Diels-Alder (Povarov) reaction of N-arylimmes with strained norbomene-derived dienophiles. 

Imino-Diels-Alder reaction [49] containing the coupling of imine and electron-rich alkene gradually became a powerful tool for the synthesis of quinazohne derivatives [50], In Povarov imino-Diels-Alder reaction, aniline and ethyl glyoxalate were chosen as substrates. And two molecules of a-iminoesters, which were obtained from the condensation of aniline and ethyl glyoxalate, were hypothesized to form the direct additive product. Cascade imino-Diels-Alder reaction conducted by Chenetal. [51] (Scheme 13.11) was extended from the Povarov imino-Diels-Alder reaction. In this research, researchers chose the same substrates as in the Povarov imino-Diels-Alder reaction, adopted various kinds of Lewis acids as catalysts, and finally produced quinazoline derivatives. Iron powder was determined as the optimized catalyst with highest yields. 

The first enantioselective Povarov reactions were two-component processes catalyzed by chiral complex of Lewis acids, but gave only modest results in terms of conversion and diastereo- and enantioselectivities [63]. Better results were obtained by Akiyama using a chiral Brpnsted acid derived from (/ )-BINOL (79) to catalyze the reaction of alkyl vinyl ethers with aromatic imines derived from o-hydroxyanilines, which gave derivatives of 8-hydroxytetrahydroquinoline 80 in good yields, with excellent diastereoselectivities and enantiomeric excesses. The authors attribute these results to the formation of a cyclic transition state wherein the chiral catalyst coordinates with both the OH and imine nitrogen, driving the attack of the nucleophile by ih Re face of the imine (Schemes 3.22 and 3.24) [64]. 

Barluenga and coworkers have studied a strategy leading to spiro tetrahydroquino-lines 142 by combination of a platinum-catalyzed intramolecular hydroxyalkoxy-lation of alkynols, which furnishes in situ exocyclic enol ethers 141, with a Lewis acid-catalyzed Povarov reaction. The starting imine required for this reaction was also generated in situ, from the corresponding aniline and aldehyde (Scheme 3.43) [93]. 

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