Imino acids cycloaddition reactions

In contrast LP-DE gives disappointing results for intramolecular imino Diels-Alder reactions, even in the presence of CSA. This is due to the fact that weak acids become strong acids in highly polar media such as 5.0m LP-DE and the protonation of diene, with concomitant diene isomerization, competes with cycloaddition [42]. This observation was supported by using trifluoroacetic acid (TEA). The imine 33 (Scheme 6.21) in LP-DE at room temperature in the presence of TEA gave a 1 1 mixture of cycloadduct 34 and the isomerized diene 35 within the unreacted imine 33. No Diels-Alder cycloadduct 36 was detected. 

The (2 + 2)-cycloaddition reactions of ketenes with heterocycles via an endocyclic imino group have contributed substantially to the synthesis of penicillin (92a) and cephalosporin C (93a) antibiotics and structurally related heterobicyclic /Mactams.7 11 Reactions with relatively stable ketenes, e.g., diphenylketene, have been reported as well as reactions of heterocycles with mixtures of acid chlorides and tertiary amines. 

The synthesis of optically active thiazolo[3,2-fl]pyridinones has been described. Chiral thiazolines 27, prepared from the condensation of imino ethers 25 with (R)-cysteine methyl ester 26, undergo a ketene-imine cycloaddition reaction with Meldrum s acid derivatives 28 to give thiazolo[3,2-a]pyridinones 29 in good yields <01JOC6756>. 

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. ... 

Kobayashi et al. were the first to report the use of lanthanide triflates as catalysts in imino Diels-Alder reactions [9], The successful three-component cyclocondensation of an aldehyde, amine and diene in acetonitrile was realized in the presence of lanthanide triflates as the Lewis-acid catalyst. This process is reminiscent of the protonated iminium-ion-based methodologies whereby the coordinated imine formation and [4+2] cycloaddition occur in one pot. 

Dipolar cycloaddition of nitrile oxide at the C=N bond of indole imino esters 130, followed by elimination of the alcohol moity gives oxadiazole derivatives 131 (Scheme 1.26) (298). Reaction of N-arylbenzamidines with arenenitrile N-oxides (generated in situ from oximoyl chlorides) produce unstable 5-amino-4,5-dihydro-1,2,4-oxadiazoles which, on aqueous acidic treatment hydrolyze to open-chain N-benzoyloxy-N -arylareneamidines (299). 

Chiral Auxiliary for Asymmetric Induction. Numerous derivatives of (—)-8-phenylmenthol have been utilized for asymmetric induction studies. These include inter- and intramolecular Diels-Alder reactions, dihydroxylations, and intramolecular ene reactions of a,p-unsaturated 8-phenylmenthol esters. These reactions usually proceed in moderate to good yield with high diastereofacial selectivity. a-Keto esters of 8-phenylmenthol (see 8-Phenylmenthyl Pyruvate) have been used for asymmetric addition to the keto group, as well as for asymmetric [2 -F 2] photoadditions and nucleophilic alkylation. Ene reactions of a-imino esters of 8-phenylmenthol with alkenes provide a direct route to a-amino acids of high optical purity. Vinyl and butadienyl ethers of 8-phenylmenthol have been prepared and the diastereofacial selectivity of nitrone and Diels-Alder cycloadditions, respectively, have been evaluated. a-Anions of 8-phenylmenthol esters also show significant diastereofacial selectivity in aldol condensations and enantiose-lective alkene formation by reaction of achiral ketones with 8-phenylmenthyl phosphonoacetate gives de up to 90%. ... 

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 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. 

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