Imino dienophile

Aza Diels-Alder Reactions of Azadienophiies 193 Tab, 5,3 Catalytic enantioselective aza Diels-Alder reactions using imino dienophiles (1)... 

The first enantioselective aza-Diels-Alder reactions of imino dienophiles on use of a chiral zirconium catalyst [116]... 

Diels-Alder, imino dienophiles, 65, 2 Diels-Alder, intramolecular, 32, 1 Diels-Alder, maleic anhydride, 4, 1 [4 -h 3], 51, 3 of enones, 44, 2 of ketenes, 45, 2 of nitrones and alkenes, 36, 1 Pauson-Khand, 40, 1 photochemical, 44, 2 retro-Diels-Alder reaction, 52, 1 53, 2 [6-h4], 49, 2 [3-h2], 61, 1 Cyclobutanes, synthesis ... 

Although several Lewis acids are known to catalyze the hetero-Diels-Alder reaction involving imino-dienes or imino-dienophiles (aza-Diels-Alder reaction), a large amount of the catalyst is often necessary. Bi(0Tf)3-xH20 showed higher activity than lanthanide triflates in catalyzing the reactions of imines with Danishefsky s diene (Scheme 15) [72]. 

A synthesis of ( )-tylophorine (213) has been based on the discovery that vanadyl trifluoride (VOF3) can be used to convert 1,2-diarylethylene into phenanthrenes in high yield. In the top sequence shown in Scheme 34, ring closure is accompanied by dehydrogenation (77CC826). In a second synthesis, ( )-tylophorine (213) is the result of an intramolecular version of a Diels-Alder cycloaddition of a conjugated diene with an imino dienophile (Scheme 34, lower sequence) (79JA5073). 

The formation of tetrahydropyridines by reaction of a suitable diene with an imino dienophile is a reaction known since more than half a century [177] and has been intensively studied. In general, the imines react as the electron-deficient component and their reactivity strongly depends on the electron density which may be tuned by activating or deactivating moieties. However, exceptions from this rule are possible as found by Padwa et al. [178]. They described cycloadditions of imines to bis(phenylsulfonyl)-1,3-butadienes. 

Hetero Diels-Alder reactions with imino dienophiles have been employed as key step in several syntheses of naturally occuring alkaloids. With regard to stereoselective transformations, the approach to (S)-anabasin worked out by Kunz et al. impressively illustrates the high utility of natural carbohydrates as source of chirality in asymmetric synthesis [505]. The N-galactosyl imine 7-28 underwent a Lewis acid catalysed aza Diels-Alder reaction with Danishefsky s diene which proceeded with excellent induced diastereoselectivity to yield the adduct 7-29. A short sequence then afforded the desired alkaloid 7-30. This work also deals with the suitability of several other dienes and imino dienophiles for such transformations (Fig. 7-7). 

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],... 

Further applications of imino dienophiles to the synthesis of natural or biologically active compounds have been directed to (-)-cannabisativine [508] and HIV-1 protease inhibitors [509] Bailey s investigations of the enantioselective synthesis of pipecolic acid derivatives have already been discussed in Sect. 3.1. 

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). ... 

A few instances of neutral acyclic A(-acyl imino dienophiles have been reported. Some of these imines can be prepared and isolated, but often they are generated in situ. For example, Wittig chemistry... 

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. 

As for the oxo-Diels-Alder reaction, not much has been reported other Lewis acids are usually superior [26]. As for the aza-Diels-Alder reaction, enantioselective reactions between imino dienophiles 60 and diene 61, using a chiral binaphtholzirco-nium catalyst 23, are known (Eq. 26) [27]. 

N-Acylimines and A-acyliminium species are the most thoroughly studied and widely used class of imino dienophiles. The first reports of Diels-... 

An imino cumulene acts as an imino dienophile with a few cyclic dienes as shown in Scheme 2-VIII. However, with 2,3-dimethylbutadiene a mixture of [4 + 2] and [2 + 2] cycloadducts were produced. With butadi-... 

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