Tetrahydroquinoline derivatives

A synthesis for the enantiomerically pure 535 was developed starting with D-phenylalanine which upon reaction with methyl chloroformate gave 528 whose reaction with methoxylamine afforded 529. Cyclization with bis(trifluoroacetoxy)iodobenzene in presence of trifluoroacetic acid gave the tetrahydroquinoline derivative 530 which was demethoxylated to give 531. Treatment of 531 with either benzyl chloroformate or... 

Other substrates were tested the results are summarized in Table 5.2. Vinyl ethers (2b-2d) also worked well to afford the corresponding tetrahydroquinoline derivatives (3a-3e) in good to high yields with good to excellent diastereo- and en-antioselectivity (entries 1-10). Use of 10 mol% of the chiral catalyst also gave the adducts in high yields and selectivity (entries 2 and 6). As for additives, 2,6-di-t-bu-... 

Catalytic asymmetric aza-Diels-Alder reactions using a chiral lanthanide Lewis acid. Enantioselective synthesis of tetrahydroquinoline derivatives using a catalytic amount of a chiral source [98]... 

Lanthanide triflates catalyze the Diels-Alder reaction of imines, generated from anilines and aldehydes, with both dienes and alkenes [26]. Thus N-benzyl-ideneaniline in the presence of Yb(OTf)3 (Scheme 6.16) reacts in organic solvent with open-chain dienes, such as Danishefsky s diene, to give tetrahy-dropyridine derivatives, while with cyclopentadiene and vinylethers and vinylthioethers it works like azadiene in both organic solvent and aqueous medium, affording tetrahydroquinoline derivatives. 

By reacting aniline with 2,3-dihydrofuran or dihydropyran and a catalytic amount of Lewis acid such as indium chloride in water, various tetrahydroquinoline derivatives were obtained by Li via an in-situ hetero-Diels-Alder reaction.130 Alternatively, similar compounds... 

Scheme 7.19. Indium-mediated domino reaction for the synthesis of tetrahydroquinoline derivatives...

The preparation of quinoline and tetrahydroquinoline derivatives from metal carbonyl-catalyzed reactions of Schiff bases with alkyl vinyl ethers in... 

As shown in Scheme 5.23, 1,2,3,4-tetrahydroquinoline derivatives were synthesized using 3-(2-aminophenyl)propanols as starhng materials and catalyzed by the I/K2CO3 system. This catalytic system was also applicable to the synthesis of 2,3,4,5-tetrahydro-l-benzazepine from 4-(2-aminophenyl)butanol. 

Zhang W, Guo YP, Liu ZG, Jin XL, Yang L, Liu ZL (2005) Photochemically catalyzed Diels-Alder reaction of arylimines with N-vinylpyrrohdinone and N-vinylcarbazole by 2,4,6-triphenylpyrylium salt synthesis of 4-heterocycle-substituted tetrahydroquinoline derivatives. Tetrahedron 61 1325-1333... 

Bismuth(III) Bromide-Catalyzed Synthesis of Substituted Tetrahydroquinoline Derivatives... 

Substituted tetrahydroquinoline derivatives are of considerable interest due to the range of their biological activities and presence in a variety of natural products... 

Scheme 5 Bismuth(III) bromide-catalyzed synthesis of substituted tetrahydroquinoline derivatives...

Zhang J, Li C-J (2002) InCl3-catalyzed domino reaction of aromatic amines with cyclic enol ethers in water a highly efficient synthesis of new L2,3,4-tetrahydroquinoline derivatives. J Org Chem 67 3969-3971... 

Savitha G, Perumal PT (2006) An efficient one-pot synthesis of tetrahydroquinoline derivatives via an aza Diels-Alder reaction mediated by CAN in an aqueous medium and oxidation to heteroaryl quinolines. Tetrahedron Lett 47 3589-3593... 

Sridharan V, Avendano C, Menendez JC (2008) New findings on the cerium(IV) ammonium nitrate catalyzed Povarov reaction stereoselective synthesis of 4-alkoxy-2-aryl-l,2,3,4-tetrahydroquinoline derivatives. Synthesis 1039-1044... 

Di Salvo A, Spanedda MV, Ourevitch M, Crousse B, Bonnet-Delpon D (2003) Uncatalyzed domino reaction in hexafluoroisopropanol a simple protocol for the synthesis of tetrahydroquinoline derivatives. Synthesis 14 2231-2235... 

Rogers JL, Emat JJ, Yung H, Mohan RS (2009) Environmentally friendly organic synthesis using bismuth compounds Bismuth(III) bromide catalyzed synthesis of substituted tetrahydroquinoline derivatives. Catal Commun 10 625-626... 

Fig. 31 Synthesis of enantiopure sugar-derived tetrahydroquinoline derivatives...

Akiyama applied Im in the inverse-demand aza-Diels-Alder reaction of various acyclic and cyclic vinyl ethers with N-aryl imines derived from o-hydroxyaniline to provide ophcally active tetrahydroquinoline derivatives (Scheme 5.16) [29]. Since aldimines derived from p-methoxyaniline gave no cycloaddition product, a nine-membered cyclic TS (akin to that proposed for the author s Mannich reachon) was invoked to rationalize the high levels of enantio-control. 

Imines derived from aniline and glyoxylic acid esters can be regarded as electron-poor 2-azadienes, in which an aromatic carbon—carbon double bond takes part of the diene system. In this context, Prato and Scorrano et al. were able to achieve the [4 + 2] cycloaddition of ethyl N-phenyl glyoxylate imines with dihydrofuran and indene leading to hexahydrof-uro[3,2-c]- and tetrahydro-7//-indeno[2,l-c]quinolines, respectively, in moderate to good yields (88JHC1831). Similarly, tetrahydroquinoline derivatives were formed by [4 + 2] cycloaddition of 1,2-bis(trimethylsily-... 

That hydrogen is set free is proved by the reduction of some of the quinoline derivative to a tetrahydroquinoline derivative. A mixture of two aldehydes, or of an aldehyde and a ketone, may be employed. (B., 20, 1098.)... 

The tetrahydroquinoline derivative 1 was treated with MCPBA in methylene chloride at room temperature in the expectation that the product would be the tricyclic compound 2. Despite a number of attempts, however, 2 was not formed. The product, obtained in 30% yield, was shown to be 3. 

A 1,3-dipolar cycloaddition using oxime derivatives yielded the tetrahydroquinoline derivative 25 (Equation 58) <2005S3423>. It was advantageous that the product precipitated out of the aqueous reaction medium in excellent yield. Carbenoid-insertion reactions have been demonstrated to produce the ring-extended quinolone structure 26 from simple substituted anilines (Equation 59) <2003TL7433>. The C-H insertion onto the aromatic ring can vary. 

A similar two-step sequence, beginning with the protected o-methoxy phenolic amines 155, provides access to the indoline and tetrahydroquinoline derivatives 156, while oxidation of the amides 157 with DAIB and... 

An intramolecular cycloaddition reaction results in the simultaneous formation of two new rings. Examples include the formation of a tetrahydroquinoline derivative (Section 4.4.2.3.4), the asymmetric synthesis of 1,2-oxazine derivatives (Section 4.3.2.4.2), and the preparation of a hcxahydrothiazino 2,3vz]quinolinc (Section 4.6.3.4) by intramolecular... 

Tetrahydroquinoline derivatives can be obtained by cycloaddition of aromatic imines or immonium salts with enamines having an a-hydrogen186,187. Anodic oxidation of A,A-dimethylaniline 323 in methanol to a-methoxylated compound 324 and subsequent... 

The Brpnsted acid catalyzed enantioselective hydrogenation of the corresponding readily available 2-substituted quinolines (for an interesting approach to 2-alkyl tetrahydroquinolines by an aza-xylene Diels-Alder reaction, see Steinhagen and Corey 1999 Avemaria et al. 2003), which we prepared by simple alkylation of 2-methylquinoline, generated the tetrahydroquinoline derivatives in excellent enantioselectivities and subsequent A-methylation gave the desired natural products in good overall yields (Fig. 5). 

Fig. 17.14 (a) The binding of tetrahydroaminoquinoline scaffold-based small molecules (65 and 66) with Bcl-XL using fully N-labeled NMR experiments, (b) The interactions tetrahydroquinoline derivative, 66 with Bcl-XL (NMR and in silico)... 

M., Khadem, S., Leek, D. M., Arya, P. (2006) Part 1. Modular approach to obtaining diverse tetrahydroquinoline-derived polycyclic skeletons for use in high-throughput generation of natural-product-hke chemical probes. Journal of Combinatorial Chemistry, 8, 715-734. 

Li s group prepared a series of substituted 2-(hydroxyalkyl)tetrahydroquinoline derivatives 2-619 and 2-620 starting from anilines 2-617 and cyclic enol ethers 2-618 in the presence of catalytic amounts of InCl3 (Scheme 2.141) [322], Good yields of 73-90% were obtained with an electron-donating or no substituent R at the aniline moiety. 

In the presence of 10 mol % Sc(OTf)3, A-benzylideneaniline reacts with 2-trans-l-methoxy-3-trimethylsiloxy-l, 3-butadiene (Danishefsky s diene) [23] to afford the corresponding aza Diels-Alder adduct, a tetrahydropyridine derivative, quantitatively (Eq. 7) [24]. In the reaction of A -benzylideneaniline with cyclopentadiene under the same conditions, on the other hand, the reaction course ehanged and a tetrahydroqui-noline derivative was obtained (Eq. 8). In this reaction, the imine aeted as an azadiene toward one of the double bonds of cyclopentadiene as a dienophile [25]. In the reaction with 2,3-dimethylbutadiene a mixture of tetrahydropyridine and tetrahydroqui-noline derivatives was obtained. A vinyl sulfide, a vinyl ether, and a silyl enol ether worked well as dienophiles to afford the tetrahydroquinoline derivatives in high yields [26,27]. 

Sc(OTf)3-catalyzed three-component coupling reactions of aldehydes, amines, and dienes have been examined. In the presence of 10 mol % Sc(OTf)3 and magnesium sulfate, benzaldehyde was treated with aniline and Danishefsky s diene. The desired three-component reaction proceeded smoothly to afford the corresponding tetrahydropyridine derivative in 83 % yield (Eq. 9) [24b]. Under the same reaetion conditions, cyclopentadiene was used instead of Danishefsky s diene to afford the corresponding tetrahydroquinoline derivative (Eq. 10). Different combinations of aldehydes, amines, and alkenes are possible in these reactions, and afford diverse tetrahydroquinoline derivatives in high yields. 

---