Hetero Diels-Alder reaction 3-amino acid

Development and application of hetero Diels-Alder reactions with participation of amino acid-derived chiral acylnitroso compounds 98T1317. 

Vogt P. E., Miller M. J. Development and Applications of Amino Acid-Derived Chiral Acylnitroso Hetero Diels-Alder Reactions Tetrahedron 1998 54 1317 1348 Keywords nitroso and acylnitroso dienophlles, befero-Dlels-Alder reaction... 

Furthermore, oxazoles of type 9-82 bearing a secondary amino functionality can be converted into pyrrolo[3,4-b]pyridines 9-86 by reaction with appropriate acid chlorides 9-83 in a triple domino process consisting of amide formation/hetero Diels-Alder reaction and retro-Michael cycloreversion via 9-84 and 9-85 (Scheme 9.17). The pyrrolo[3,4-fc]pyridines can be obtained in even higher yields when the whole sequence is carried out as a four-component synthesis in toluene. Here, 1.5 equiv. NH4C1 must be added for the formation of the now intermediate oxazoles [56b]. 

An extensive review of the hetero-Diels-Alder reactions of 1-oxabuta-1,3-dienes has been published. Ab initio calculations of the Diels-Alder reactions of prop-2-enethial with a number of dienophiles show that the transition states of all the reactions are similar and synchronous.Thio- and seleno-carbonyl compounds behave as superdienophiles in Diels-Alder reactions with cyclic and aryl-, methyl-, or methoxy-substituted open-chain buta-1,3-dienes.The intramolecular hetero-Diels-Alder reactions of 4-benzylidine-3-oxo[l,3]oxathiolan-5-ones (100) produce cycloadducts (101) and (102) in high yield and excellent endo/exo-selectivity (Scheme 39). A density functional theoretical study of the hetero-Diels-Alder reaction between butadiene and acrolein indicates that the endo s-cis is the most stable transition structure in both catalysed and uncatalysed reactions.The formation and use of amino acid-derived chiral acylnitroso hetero-Diels-Alder reactions in organic synthesis has been reviewed. The 4 + 2-cycloadditions of A-acylthioformamides as dienophiles have been reviewed. ... 

In 2006, Akiyama and coworkers established an asymmetric Brpnsted acid-catalyzed aza-Diels-Alder reaction (Scheme 36) [59]. Chiral BINOL phosphate (R)-3o (5 mol%, R = 2,4,6- Pr3-CgH2) bearing 2,4,6-triisopropylphenyl groups mediated the cycloaddition of aldimines 94 derived from 2-amino-4-methylphenol with Danishefsky s diene 95 in the presence of 1.2 equivalents of acetic acid. Piperidinones 96 were obtained in good yields (72 to >99%) and enantioselectivi-ties (76-91% ee). While the addition of acetic acid (pK= 4.8) improved both the reactivity and the selectivity, the use of benzenesulfonic acid (pK= -6.5) as an additive increased the yield, but decreased the enantioselectivity. A strong achiral Brpnsted acid apparently competes with chiral phosphoric acid 3o for the activation of imine 94 and catalyzes a nonasymmetric hetero-Diels-Alder reaction. The role of acetic acid remains unclear. 

Diels-Alder and hetero-Diels-Alder Reactions Using a-Amino Acid Derivatives as Organocatalysts... 

A short asymmetric synthesis of the 2-ketocarbacepham (27) involving as the initial step for the preparation of the starting piperidone, a hetero Diels-Alder reaction of the benzylimine derived from the enantiomer of Gamer s aldehyde with Danishesky s diene, has been described <02JOC598>. The key cyclization step to form the bicyclic P-lactam system was achieved from a P-amino acid precursor using the Mukaiyama reagent, 2-chloro-A-methylpyridinium iodide. 

The multitude of hetero Diels-Alder reactions found in the literature clearly demonstrates the importance of this transformation. Thus, this type of cycloaddition is today one of the most important methods for the synthesis of heterocycles. Striking features of this method are the tremendous diversity, excellent efficiency especially in those cases where the reactive dienes and dienophiles are formed in situ, and high stereoselectivity in many cases. There is a broad scope and only little limitation. In recent years the use of Lewis acid, the development of diastereoselective and enantioselective reactions as well as the application of high pressure gave an enormous push. In addition, many of the obtained heterocycles can be transformed into acyclic compounds allowing the stereoselective preparation of e.g. amino and hydroxyl functionalized open chain compounds or even carbocycles to be of interest. Also, for the synthesis of natural products, the hetero Diels-Alder reaction is of great value. Since heterocycles,... 

The domino process probably involves the chiral enamine intermediate 2-817 formed by reaction of ketone 2-813 with 2-815. With regard to the subsequent cycloaddition step of 2-817 with the Knoevenagel condensation product 2-816, it is interesting to note that only a normal Diels-Alder process operates with the 1,3-bu-tadiene moiety in 2-817 and not a hetero-Diels-Alder reaction with the l-oxa-1,3-butadiene moiety in 2-816. The formed spirocyclic ketones 2-818/2-819 can be used in natural products synthesis and in medicinal chemistry [410]. They have also been used in the preparation of exotic amino acids these were used to modify the physical properties and biological activities of peptides, peptidomimetics, and proteins... 

A library of chiral dihydropyrans (226) [241] was synthesized using asymmetric hetero-Diels-Alder reactions (HAD) on polymer-bound enol ethers (221) and a, 3-unsaturated oxalyl esters (222). A chiral Lewis acidic Cu -bisoxazoline complex was used because of its high efficiency, the high predictability of the reaction outcome, and its broad substrate tolerance [280]. Enol ethers were used as alkene components bearing a hydroxy function for attachment to the resin via a silyl linkage (Scheme 49). The diene components carried allyl-ester groups, which could be readily displaced by amino functions in subsequent steps of the combinatorial synthesis. 

The hetero-Diels-Alder reaction of aldehydes as the 2 component has been extensively studied of late, and this year the use of high pressure both on its own and in combination with Lewis-acid catalysis has been extended. A combination of [Eutfod) ] and high pressure (10 kbar) has been used to prepare amino... 

Hetero-Diels-Alder reactions have been used in the construction of amino-sugars, asymmetry being induced by the use of either a chiral Lewis acid catalyst or a chiral auxiliary. Thus, the 3-amino-hexuronic acid derivatives 61 were obtained with high de and ee using a copper(II) triflate catalyst with a chiral bisoxazoline ligand. 4-Amino-4-deoxy-D-erythrose and 4-amino-4,5-dideoxy-L-lyxose (63), the latter a potent inhibitor of a-L-fucosidase, were obtained from the D-pyroglutamic add-containing diene 62 (Scheme 19). ... 

The approach developed by Danishefsky and co-workers for the construction of sugar derivatives (see Vol.l6,p.126), which employs the initial synthesis of a dihydropyrone derivative by a Lewis acid-catalyzed hetero-Diels-Alder reaction, has been extended to the synthesis of the glycoside derivative (36), x>f DL-llncosamine (Scheme 10). Introduction of the amino-function at C-6 required a circuitous approach Involving 6,7-bromohydrin, 6,7-epoxide, and N-substituted 6,7-aziridine intermediates. ... 

The enantioselective intramolecular formal 2+4-cycloaddition of acrylates and a, -unsaturated imines (99) catalysed by chiral phosphines (100), derived from amino acids, produced A-heterocycles (101) (Scheme 31). Chiral dirhodium(II) carboxamidates (102) catalysed the hetero-Diels-Alder reactions between 2-aza-3-silyloxy-l,3-butadienes and aldehydes to yield all cw-substituted l,3-oxazinan-4-ones in high yields and high enantioselectivity (98% ee)P The nickel-catalysed 4 + 2-cycloaddition of a, -unsaturated oximes with alkynes yielded 2,3,4,6-tetrasubstituted pyridine derivatives. The reaction of isoquinoline, an activated alkyne, and 4-oxo-4//-l-benzopyran-3-carboxaldehyde (103), in ionic solvents, produced 9a//,15//-benzo[a][l]benzopyrano[2,3-/t]quinolizine derivatives (105) via the zwitterion (104) selectively and in good yields (Scheme 32).The Diels-Alder cycloaddition of ethyl 3-(tetrazol-5-yl)-l,2-diaza-l,3-butadiene-l-carboxylates with -rich heterocycles, nucleophilic olefins, and cumulenes formed 3-tetrazolyl-l,4,5,6-tetrahydropyridazines regioselectively. The silver-catalysed formal inverse-electron-demand Diels-Alder... 

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