Cycloaddition reactions Diels-Alder, imino dienophiles

As a rule, cycloadditions with acyclic -acyl imino dienophiles are useful synthetic reactions which demonstrate excellent regio- and stereo-selectivity. A commonly used source of IV-acyl immonium dienophiles are bis-urethanes such as (13) (equation S), which upon treatment with a Lewis acid and a diene afford Diels-Alder adducts. In this case, (13) reacts with boron trifluoride etherate to afford immonium ion (14) which adds to diene (15), yielding tetrahydfopyridine (16). ... 

Two very elegant alkaloid syntheses basing on intramolecular cycloadditions of imino dienophiles have been published by Grieco and his coworkers. The preparation of ( )-eburnamonine 7-32 is very efficient since imine 7-31, available from (5-valerolactam in a straightforward sequence, is directly converted into the desired alkaloid 7-32 by aza Diels-Alder reaction and subsequent isomerisation of the newly formed double bond. (Fig. 7-8) [506],... 

A subset of imino-Diels-Alder cycloadditions involving reactions between N-aryl imines and electron-rich dienophiles is the Povarov reaction [75]. 

A number of diverse stmctural types of cyclic imino dienophiles have been used in cycloadditions. For instance, dehydrohydantoins are useful partners in hetero Diels-Alder reactions. Two methods have been developed for in situ generation of these species. In one tqjproach, methoxyhydantoins such as (24) (equation S) are heated or are treated with acid to promote elimination of methanol, affording dienophile (25).22- This intermediate can be trapped regio- and stereo-selectively with 1,3-dienes. For example, with 1,3-cyclohexadiene only endo adduct (26) is formed. There is no ambiguity in this case concerning the dienophile configuration, and thus product (26) clearly derives from an endo transition state. 

Several examples exist of inverse electron demand Diels-Alder reactions involving electron-deficient sym-tetrazines acting as dienes. However, the neutral, electon-rich imino compounds involved in these cycloadditions do not generally e pear to be useful dienophiles with other types of dienes. 

Table 2-II lists a number of representative imino Diels-Alder cycloadditions using acyclic IV-acylimines and Ai-acyliminium dienophiles. In general, cycloadditions using C.iV-diacylimino systems (entries 1-10) and unsymmetrical dienes show good regioselectivity. The adducts from these reactions have the regiochemistry one would predict based on Scheme 2-1...

Cycloadditions of iminium compounds with 1,3-dienes to afford Diels-Alder adducts seems to be a reaction of general applicability.46 On the other hand, simple electron-rich imino species are less reliable dienophiles. Some electron-rich imines will undergo Diels-Alder reactions under acid catalysis and thus are probably actually reacting as iminium salts. However, inverse electron demand [4 + 2] cycloadditions of neutral imines with electron-deficient dienes have been reported, as have additions to exceptionally reactive dienes (vide infra). 

As alluded to above, no detailed studies of the mechanism of the imino Diels-Alder reaction have been reported to date. However, it has been suggested that [4 + 2] cycloadditions of most C=N, N=N, C=0 and N=0 dienophiles are HOMOdiene-LUMOdienopwie controlled. Whether, in fact, these reactions are concerted pericyclic processes has yet to be firmly established. In any case, a simple dipolar mechanistic model (Scheme 2-1) can often be used to qualitatively predict the regiochemistry of imino dienophile cyclizations with unsymmetrical dienes, which usually proceed with high selectivity. This model may, in fact, be indicative... 

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. ... 

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