Amines quinolines, 1,2,3,4-tetrahydro

Other secondary amines such as pyrrolidine, di- -butylamine, tetrahydro-quinoline, n-benzylamine, and piperidine were also found to be capable of effecting this reduction. Interestingly, morpholine does not reduce enamines as readily (47) and its acid-catalyzed reaction with norbornanone was reported (45) to give only the corresponding enamine (93), although trace amounts of the reduction product were detected when cyclohexanone was treated with morpholine under these conditions (47a). The yield of morpholine reduction product was increased by using higher temperatures. 

Reaction of 3-benzamido-2,5-dioxo-5,6,7,8-tetrahydro-(2ff)-l-benzopyrans 58 with nitrogen-containing nucleophiles (amines and hydrazines) provides the corresponding quinolin-2-(l//)-ones 59 <96H(43)809>. 

A solid-phase-supported version of the Pictet-Spengler reaction has been demonstrated for the synthesis of mono- and disubstituted tetrahydro-P-carbolines [40,41], Disubstituted quinolines have been prepared via solid-phase synthesis utilizing three classes of building blocks aiyl methyl ketones, (Q-functionalized acids, and primary amines [42],... 

For the preparation of 4-(1.2.3.4-tetrahydroquinolino)-phenol 17 three different procedures were worked out [Eqs. (6)-(8)]. 17 was prepared by reacting N-p-methoxyphenyl-anthranilic acid with acetic anhydride and subsequent saponification to l-p-methoxyphenyl-4-hydroxy-2-quinolone, reaction withPOCl3 to form l-p-methoxyphenyl-4-chloro-2-quinolone, hydrogenation to l-(p-methoxy-phenyl)-3.4-dihydro-2-quinolone, splitting the ether with HBr to l-(p-hydroxy-phenyl)3.4-dihydro-2-quinolone, and reduction with LiAlH4 [Eq. (6)J. Another synthetic possibility was the reaction of p-anilinophenol with (3-propiolactone and subsequent cyclization to l-(p-acetoxyphenyl)2.3-dihydro-4-quinolone 18. The next step, the Wolff-Kishner reduction, led directly to the desired product [Eq. (7)]. The third way, the direct amination of p-iodoanisole with 1.2.3.4-tetrahydro-quinoline and the subsequent splitting of 4-(1.2.3.4-tetrahydro-quinolino)-anisol with HBr was the best one [Eq. (8)]. Saponification of l-(p-acetoxyphenyl>2.3-... 

The eventual product of such reactions (after cleavage of the Zr-C bond during workup [51]) is an amine with a vinyl or alkyl substituent (arising from the alkyne or alkene) at the a position. Whitby thus derivatized tetrahydro-quinoline, following in situ generation of the zirconaaziridine 26, by alkyne, alkene, or allene insertion (Eq. 11) [52,53]. 

Weidner ef alP described a one-pot Smiles rearrangement method for the synthesis of various aminoquinolines from the corresponding hydroxyquinolines and showed that the tendency for the conversion depends on the electron-deficient nature of the quinolines. In a specific example, the reaction of 15 with (i) 2-bromo-2-methylpropionamide, 3 equiv. each of NaH and cesium carbonate in dioxane at reflux for 16 h and (ii) N-methylpyrrolidinone (NMP), l,3-dimethyl-3,4,5,6-tetrahydro-2(l//)-pyrimidinone (DMPU) (10 1 ratio) and 1 equiv. of NaH at 150 C for 72 h afforded the amine 16. 

The Povarov reaction is related to the previous examples in that it can be defined as the formal imino Diels-Alder reaction between aromatic imines and electron-rich olefins. It is one of the most popular methods for the synthesis of tetrahydro-quinolines [40], and two examples of Povarov reactions in water are summarized in Scheme 1.27. In an eaily example of the use of ceric ammonium nitrate as a catalyst in synthesis [41], Perumal reported a few examples of a CAN-catalyzed Povarov reaction of aldehydes, amines and N-viitylpyrroUdin-2-ones as the olefin component in water for the synthesis of heteroaiyl-substituted tetrahydroquinolines 54 [42]. Using a different approach, Vaultier later described an onium salt-supported Povarov three-component reaction in water at room temperature affording tricyclic compounds 55. In this study, either the aldehyde or the amine components were linked to a side chain containing an onium salt, which confers solubility to the reactant [43]. 

One final example that underscores the power of intramolecular domino reactions to achieve the stereoselective synthesis of complex nitrogen heterocycles comes from the work of Barluenga and Gonzalez, who studied the preparation of tetrahydro-quinolines by intramolecular arylation of olefins induced by the in-house developed IPy2BF4 iodonium reagent. When applied to amine 102, this method afforded the tetracyclic compound 103 by the creation of three rings and five stereocenters in an elegant, fully diastereoselective cationic cyclization cascade (Scheme 3.32) [79]. 

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