Indolizine reduction

Reduction of isoindoles with dissolving metals or catalytically occurs in the pyrrole ring. Reduction of indolizine with hydrogen and a platinum catalyst gives an octahydro derivative. With a palladium catalyst in neutral solution, reduction occurs in the pyridine ring but in the presence of acid, reduction occurs in the five-membered ring (Scheme 38). Reductive metallation of 1,3-diphenylisobenzofuran results in stereoselective formation of the cw-1,3-dihydro derivative (Scheme 39) (80JOC3982). 

Indolizine, 1 -cyano-2-(methylthio)-synthesis, 4, 465 Indolizine, 3,5-dialkyl-synthesis, 4, 475 Indolizine, dihydrosynthesis, 4, 467, 468 Indolizine, dimethyl-mass spectrometry, 4, 187 Indolizine, 1,2-dimethyl-oxidative dimerization, 4, 458 Indolizine, 2,6-dimethyl-cycloaddition reaction, 4, 460 reduction, 4, 459... 

A third method for the synthesis of cycl[3.2.2]azines, from iV-(aroylmethyl)pyridinium salts via indolizines, involves intramolecular (reductive) McMurry coupling of the latter. For example, 3,5-dibenzoylindolizines, obtained from 2-benzoyl-iV-phenacylpyridinium bromide as shown (Scheme 91), are cyclized using zinc and titanium(iv) chloride to give the 3,4-diphenylcyclazines 352 in high yield (>90%). The reaction cannot be applied, however, to... 

Indolizines were arylated under similar conditions selectively in the 3-position (6.90.). A detailed mechanistic study of the transformation revealed that in this reaction the arylpalladium species, formed in the first step of the catalytic cycle, is attached to the indolizine core in an electrophilic substitution step, which is followed by reductive elimination. The presence of alternate routes such as Heck-type insertion, oxidative addition of the C-H bond, or transmetalation were excluded on the basis of experimental evidence.121... 

Ames and co-workers have reported the synthesis of some aminoethyl indolizines.141 Workers at Keele University have investigated the preparation of hydroxymethyl and aminomethyl derivatives.142 They obtained the 2-, 3-, and 6-hydroxymethyl compounds by lithium aluminum hydride (LAH) reduction of the esters. However, compound 93 gave inseparable mixtures on reduction, and whereas the 2-amino-methyl compound could be made by reduction of the corresponding... 

Indolizines with a saturated six-membered ring may be obtained from pyrrole or furan derivatives.225,226 The reaction of 3,4-dimethylpyrryl-magnesium bromide with y-chlorobutyronitrile followed by dilute acid gave 5,6,7,8-tetrahydro-l,2-dimethyl-5-oxoindolizine. 5,6,7,8-Tetrahy-droindolizine can be obtained by the cyclodehydration of 3-(2-furyl)-propylamine over alumina at 400°C. The same product is obtained by the treatment of 3-(2-pyrryl)propyl cyanide with hydrogen chloride in the presence of boron trifluoride etherate catalyst, followed by Wolff-Kishner reduction of the intermediate ketone. 

Another type is observed in the reduction of 2-cyano-3-(2-pyridyl)methylacrylates in MeCN containing chlorotrimethylsilane to indolizines. The dihydropyridine anion attacks the cyano group with ring closure [90]. 

Reviews - Acyl anion equivalents,1 2 crown ethers in synthesis,3 intramolecular 1,3-dipolar additions,11 oxazolines in synthesis,5 oxidation-reduction condensations,6 oxythallation,7 transition metals in synthesis,8 9 and ynamines in synthesis.10 Also reviewed are syntheses of pyridines,11 pyrroles,12 and indolizines.13 Other reviews are in specific sections. 

Thioamides of two cyclopropanecarboxylic acids undergo coupling reactions with diazomethane derivatives in refluxing benzene containing rhodium(II) acetate. The reaction conceivably takes place via a thiirane intermediate which undergoes reductive elimination by reaction with excess diazo compound. An example of an intramolecular reaction is the formation of indolizine 2. If the diazo compound is not in excess a thiol is formed, this can be removed by Raney nickel desulfurization. ... 

An unusual synthesis of ( )-septicine (866) from dimethyl squarate (878) exploits rearrangement of a 4-(l-pyrrolo)cyclobutenone 879 to the indolizine-5,8-dione 880, presumably via a ketene intermediate formed by electrocyclic ring opening of 879 (Scheme 113) (584). Partial reduction of 880 yielded the 4-hydroxypyridone 881, the triflate ester of which was deoxygenated with a palladium(II)-formic acid system to yield the l,2,3,5-tetrahyi oindolizin-5-one 882. Mild reduction with aluminum hydride completed the synthesis of ( )-866 in an excellent overall yield of 27% from 878. 

Indolizine and its simple alkyl derivatives are sensitive to light and to aerial oxidation, which lead to destruction of the ring system. Catalytic reduction in acidic solution (reduction of the indolizinium cation) selectively saturates the pyrrole ring, giving a pyridinium salt complete saturation, affording indolizidines, results from reductions over platinum. ... 

More elaborate examples have been reported for example, the synthesis of bicyclic systems from two consecutive reverse Cope reactions have been demonstrated.18 Thus, upon treatment with sodium cyanoborohydride (pH 4), l,8-nonadien-5-one (53) underwent two consecutive reverse Cope reactions to yield the two epimeric N-oxides 54a and 54b. Reduction of these compounds with hexachlorodisilane gave indolizines 55a and 55b in 41% yield from 53. 

Indolizines were hydrogenated over Re2S7 catalysts. The pyridine ring was more easily hydrogenated than the pyrrole ring. Phenyl substitution did not prevent complete reduction while alkyl substituents made the reduction more difficult. Nitro groups were reduced to amino groups... 

Pyridine-substituted nicotines, nornicotines, and anabasines are available from a-cyano-amines by a new synthesis. The syntheses of ( )-[l - N]nornicotine and ( )-[l - N]nicotine have been described, from cyclopropyl 3-pyridyl ketone and [ N]formamide. 4-Methylnicotine has been prepared it shows no nicotine-like pharmacological activity. " An investigation into the stereochemical factors involved in the behaviour of nicotine and related compounds in the Menschutkin reaction has been conducted.A bridged nicotine , 1,2,3,5,6,10b-hexahydropyrido[2,3-g]indolizine (44), has been synthesized by carboxylation of the dilithium derivative of 2-methylnornicotine followed by cyclisation and reduction with borane in tetrahydrofuran. Several 5-halogeno-nicotines have been prepared and their pK values and biological activities measured. ... 

The diol XI-80, obtained by the side-chain reduction of the keto ester (XI-79) with sodium borohydride, served as a precursor to 5-methylindolizine (XI-82). However, the yield was low in this synthesis and the indolizine could be prepared by a more favorable route from the aldehyde XI-81. 

Indolizine undergoes reduction by catalytic hydrogenation in acidic medium via the indoUzinium ion 2 depending on activity of the catalyst used, the pyridinium ion 3 (Pd/C) or indolizidine (4) (Pt) is obtained ... 

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