Quinolizines synthesis

Furazano[3,4-d]pyrimidine, 7-amino-synthesis, 6, 729 UV spectra, 6, 713 Furazanopyrimidines amine synthesis from, 5, 591 synthesis, 6, 418 Furazano[3,4-d]pyrimidines nucleophilic attack, 6, 719 nucleophilic substitution, 6, 713 reduction, 6, 402 7-substituted reactions, 6, 722 Furazano[3,4-a]quinolizines synthesis, 6, 730... 

A recent quinolizine synthesis used the reactivity of both C- and N-alkyl groups in picolinium quaternary salts isa ... 

H-Quinolizine, 2-(4-chlorophenylimino)-applications, 2, 569 4H-Quinolizine, cyanotriphenyl-synthesis, 4, 469 Quinolizines reactions, 2, 547 Quinolizines, dihydroreactions, 2, 547 4H-Quinolizines oxidation, 2, 547 synthesis, 2, 568 Quinolizine-2-thiones reactions, 2, 545 synthesis, 2, 544 Quinolizine-4-thiones... 

Quinolizinium salts, 2,4,6-trimethyl-condensation reactions, 2, 539 Quinolizinones reactions, 2, 544 synthesis, 2, 567 Quinolizinones, nitro-synthesis, 2, 568 Quinolizin-4-ones nitration, 2, 529 synthesis, 2, 565 2,2 -Quinolyl... 

A further application of the Dieckmann cyclization is that leading to the synthesis of 3,4,6,12-tetrahydro-l(2jE )-indolo[2,3-6]quinolizin-l-one (398). ... 

A recent formal synthesis of the alkaloid (—)-mitralactonine relied on a reaction that allowed the simultaneous creation of three new bonds, two of them a and one ft with respect to the quinolizine nitrogen. As shown in Scheme 112, treatment of triptamine with chiral aldehyde 480 in the presence of acid directly gave a mixture of diastereo-meric indoloquinolizidines 481 and 482 through a mechanism involving a Pictet-Spengler cyclization and a N-alkylation reaction <2007SL79>. 

The DA reaction of 5-acetyl-3-methylthio-1,2,4-triazine with cyclic enamines has been used in the total synthesis of new indazolo[2,3-a]quinolizine alkaloids <06T5736>. 

Utilizing Wenkert s cyclization process, a number of new approaches have been elaborated for the synthesis of simple indolo[2,3-a]quinolizine derivatives. For example, treatment of JV-[2-(indol-3-yl)ethyl]piperidine (V-oxide (134) with trifluoroacetic anhydride gave piperideinium intermediate 135 in a Polonovski-type reaction, which could be cyclized in acidic medium to ( )-l (101). 

A short synthesis of ( )-deplancheine has been reported by Hameila and Lounasmaa (119) by lithium aluminum hydride reduction of 3-acetylin-dolo[2,3-a]quinolizine derivative 171. 

On the other hand, ( )-corynantheine was achieved from key intermediate 301, used previously in the synthesis of ajmaline (167). The fra/u-tosylhydrazone derivative 302 afforded the desired vinyl-substituted indolo[2,3-o]quinolizine 304 in moderate yield along with the corresponding ethylidene-substituted isomer. Formylation and methylation of 304 afforded finally ( )-corynantheine (164). 

A stereoselective total synthesis of ( )-hirsutine has been developed by Brown et al. (179). Catalytic hydrogenation of hydroxycyclopentenone 327, prepared previously (180), afforded a mixture of isomeric diols 328, which were quantitatively cleaved by sodium periodate to supply 329. Reductive amination of 329 with tryptamine resulted in tetrahydropyridine 330, which upon treatment with aqueous methanol in the presence of hydrochloric acid gave indolo-[2,3-a]quinolizine 321 with pseudo stereochemistry. Conversion of 321 to ( )-hirsutine was accomplished in a similar manner by Wenkert et al. (161) via selective reduction with diisobutylaluminum hydride and methylation with methanol (179). 

In 1969, Szantay and co-workers published a linear synthesis of (+)-yohimbine and (—)-P-yohimbine (75) in full detail (220). Tetracyclic key intermediate 400, obtained from 3,4-dihydro-p-carboline and a properly substituted a,p-unsatu-rated ketone (173), was treated with a proper phosphonoacetic acid derivative to give unsaturated nitrile 401 or unsaturated ester 402. Catalytic reduction of the latter resulted almost exclusively in 404 with normal stereo arrangement, while reduction of 401 supplied a mixture of normal and epialloindolo[2,3-a] quinolizines 403 and 405, respectively. Dieckmann ring closure of diester 404 gave 18a-methoxycarbonylyohimbone (407) as the thermodynamically favored... 

Kametani and his collaborators presented two different approaches for the synthesis of ( )-yohimbine and ( )-p-yohimbine 223-226). The first one (223, 224) utilizes Stork s method for the Robinson reaction of the enamine derived from octahydroindolo[2,3-a]quinolizin-2-one (414) to produce 15,16-didehydroyohimbinone (410), prepared first by Szantay et al. (74, 221). 

Another related photocyclodehydrogenation synthesis uses an N- styrylpyridinone (164 Scheme 92), which is generated by N- alkylation of pyridinone with a styryl bromide. Irradiation in acid solution in the presence of oxygen causes isomerization and cyclodehydrogenation to afford 4//-benzo[a]quinolizin-4-one (165) and its 7-phenyl derivative (166) in yields of 37% and 60% respectively (77JOC1122). 

Another type of [5 +1] reaction leading to the synthesis of an (in effect) quinolizin-4-one (198, Scheme 105) involves the concurrent replacement of the oxygen atom of a 2-benzopyrylium salt (197) by nitrogen (from ammonia), and cyclization (77CHE1183). 

Since the last extensive review1 on the chemistry of the quinolizines was presented, numerous developments have occurred in the field of natural products incorporating the quinolizine nucleus as well as in the synthesis and study of the simple quinolizine derivatives. The present chapter is confined exclusively to the contributions made in the field of the aromatic quinolizine derivatives. 

One of the significant developments in the chemistry of the quinolizines since 1954 was the synthesis of the parent aromatic system, the quinolizinium ion, which was unknown until then. This was achieved by Boekelheide and Gall2 by the condensation of 2-picolyllithium with /3-cthoxypropionaldehyde followed by the steps indicated in the sequence 2 - 3 -> 4 -> 1. 

Some variations on the above scheme have also been successfully adapted to the synthesis of other related quinolizines. One of these involves the condensation ofpyridine-2-aldehyde with deoxybenzoin13 followed by quatemization with phenacyl halides and cyclization by treatment with dibutylamine [Eq. (4)]. 

The yields are high in this synthesis. However, the use of strong acids like sulfuric acid in the cyclization step causes much tar formation and lower yields. Acetylacetone, benzoylacetone, and acetoacetaldehyde have been successfully employed as starting j8-diketones and afford the corresponding 2,4-disubstituted quinolizines in 50-75% yield. The use of 2,6-lutidyllithium as starting component gave the corresponding 2,4,6-trisubstituted quinolizines. 

Following the original pattern of synthesis worked out by Diels and Pistor 25 and with a view to verifying the structures of some of the oxidation and hydrolysis products, Acheson and Taylor26 have re-centlysynthesized 9-methyl-and 7,9-dimethyl-4/f-quinolizine-1,2,3,4-tetracarboxylic esters. On the bases of extensive oxidation and reduction studies and ultraviolet and N.M.R. spectral data, the different labile and stable adducts have been assigned the 9aH- (16, 17) or the 4//-quinolizine structures (18, 19). 

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