Alkynes quinolines from

Scheme 56 An approach to quinolines from imines and alkynes.

Sakai N, Annaka K, Konakahara T (2004) Palladium-catalyzed coupling reaction of terminal alkynes with aryl iodides in the presence of indium tribromide and its application to a one-pot synthesis of 2-phenylindole. Org Lett 6 1527-1530. doi 10.1021/ol036499u Sakai N, Annaka K, Eujita A, Sato A, Konakahara T (2008) InBr 3-promoted divergent approach to polysubstituted indoles and quinolines from 2-ethynylanilines switch from an intramolecular cyclization to an intermolecular dimerization by a type of terminal substituent group. J Org Chem 73 4160-4165. doi 10.1021/jo800464u... 

Chiba and coworkers developed a CuBr SMe2-catalyzed synthesis of highly substituted quinolines from Af-(2-alkynylaryl)enamine carboxylates under aerobic conditions via intramolecular carbooxygenation of alkynes (Scheme 8.85). 

Among the tasks remaining is the replacement of the C-16 hydroxyl group in 16 with a saturated butyl side chain. A partial hydrogenation of the alkyne in 16 with 5% Pd-BaS04 in the presence of quinoline, in methanol, followed sequentially by selective tosylation of the primary hydroxyl group and protection of the secondary hydroxyl group as an ethoxyethyl ether, affords intermediate 17 in 79% overall yield from 16. Key intermediate 6 is formed in 67 % yield upon treatment of 17 with lithium di-n-butylcuprate. 

The most useful approaches to the synthesis of di- and poly-ynes from terminal alkynes are undoubtedly the copper-catalyzed couplings discovered by Glaser (CuCl, NH4OH, EtOH, 02)," Eglinton [Cu(OAc)2, hot pyridine or quinoline, 02], and Hay [Cu(I), tmed, 02]. Some of the many applications of these reactions are discussed in the following. 

Among the simplest syntheses of this type are those of tetrahydro-quinolines or -iso-quinolines based on Friedel-Crafts cyclizations. The use of side-chain halides is shown by the synthesis of 1,2,3,4-tetrahydroisoquinolines (158) (71CC799), and of 3,4-dihydroquinol-2-ones (159) (27CB858). Electrophilic carbon atoms can be developed from secondary or tertiary alcohols, or from alkenes or alkynes. In the synthesis of the tetrahydroisoquinoline... 

Such reactions occur readily with alkynic esters, but the products isolated are often complex. Thus, the initial Michael adduct of type (68) from pyridine with acetylenedicarboxylic ester reacts with more alkynic ester to yield (66), (67) and other products. Quinoline and isoquinoline react similarly. 

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]. 

Nina A. Nedolya was born in Irkutsk (Russia) and educated in organic chemistry at the Irkutsk State University (Diploma 1972, PhD 1982, DSc 1998). From 1995 to 1999 she was associated with Prof. L. Brandsma at the Utrecht University (The Netherlands). In 1999 she obtained her second PhD from the Utrecht University. She is presently Head of the Research Group of Chemistry of Heterocyclic Compounds at A. E. Favorsky Irkutsk Institute of Chemistry. She is the author of over 210 review articles and research papers. She is also one of the inventors for 112 patents. She is interested in the chemistry of polyfunctional unsaturated heteroatomic systems (vinyl, allenyl, and alkynyl ethers and their derivatives, linear and cyclic heteropolyenes, hetero-cumulenes), including synthesis of important heterocycles, particularly pyrroles, thiophenes, thiazoles, imidazoles, dihydrofurans, dihydropyridines, pyridines, quinolines, dihydroazepines, and azepines, based on metallated allenes or alkynes and/or heterocumulenes. 

Palladium metal is too active a catalyst to allow the hydrogenation of an alkyne to stop after one equivalent of H2. To prepare a cis alkene from an alkyne and H2, a less active Pd catalyst is used— Pd adsorbed onto CaC03 with added lead(II) acetate and quinoline. This catalyst is called the Lindlar catalyst after the chemist who first prepared it. Compared to Pd metal, the Lindlar catalyst is deactivated or poisoned. ... 

Alkynes bearing electron-withdrawing substituents are more suitable for this reaction as was shown earlier by Bohlmann and Rahtz. Pyridines are formed from intermediate Michael adducts in the reaction of a-oxoalkynes having a j8-hydrogen and several primary enaminones in high yield. If, however, jS-substituted propargylaldehyde derivatives are used, a normal Hantzsch-type reaction without attack of the alkyne bond leads to 1,4-dihydropyridines (equation 79). This method was used later for converting cyclic enaminones to pyridine derivatives, however in low yield, and to quinolines in a better yield (equation 80). 

An indolizine may also be synthesized from a 2-aIlylpyridine by heating the compound at 120°C [3753]. A good yield of a tricyclic indolizine is obtained by oxidative cyclization of the alkyne (42.4) at about 5°C with MCPBA the first-formed iV-oxide undergoes a rearrangement of the alkynyl chain. Addition of a nucleophile towards the end of this one-pot synthesis leads to a peri-fused quinoline in good yield [3535]. A(-Benzyl-)V-propynylanilines undergo oxidative cyclization on treatment with a perbenzoic acid and a nucleophile (such as thiophenol or cyanide ion) under mild conditions [2784]. 

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