Dihydro indolizines

Cyclohydrocarbonylation of 1-allylpyrroles 74a-d catalyzed by Rh4(CO)i2 gave the corresponding 5,6-dihydro-indolizines 77a-d in good yield and excellent regioselectivity (Scheme 12)." This reaction proceeded through a cascade hydroformylation-cyclization-dehydration sequence (Scheme 12). Exclusive introduction of a formyl group... 

If an allyl halide is used as the quaternizing agent, an intramolecular 1,5-cyclization of the ylid may take place. In this way, various dihydro-indolizines, which are prone to oxidation and thus difficult to prepare, have been made.67 The probable mechanism is shown in Scheme 9. 

Bis-[fluoren-<9-spiro-l >-1,2-diacetyl-5,8-dimethyl-1,8a-dihydro-indolizin-7-yl]- 2840 Bis-[fluoren-<9-spiro-l >-l, 2-dimethoxyearbonyl-1,8a-dihydro-indolizin-7-yl]- 2840 Bis-[fluoren-<9-spiro-l>-l,2-dimethoxycarbonyl-5.8-dimethyl-l,8a-dihydro-indolizin-7-yl]- 2840... 

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). 

Pyrano[3,2 ]indolizines such as 120 can be prepared from the reaction of N-( 1 -benzotriazolylmethyl)indolines with 3,4-dihydro-2//-pyran under acidic or Lewis-acidic conditions (Equation 26) <2001T4933>, and a simpler analogue 122 is the end product of an annulation process starting from the enamine 121 and ethyl acrylate <1996H(43)1391> (Scheme 34). Pyrano[4,3-/]indolizinetriones, for example, 124, result from the hydrolysis of protected 2,3-dihydro-l//-indolizincdioncs 123 (Equation 27) <2000H(53)771>. 

When the reaction of enaminone (223) and dimethyl methoxymethy-lenemalonate was carried out in THF in the presence of butyllithium, pyrrolidinomethylenemalonate (224) was obtained in 4% yield. When this reaction conducted in DMF in the presence of potassium tert-butylate, pyrrolidinomethylenemalonate (224) and 2,3-dihydro- l//-indolizin-5-one (225) were prepared in 21 and 46% yields, respectively (88AP345). 

The Michael attack of the enamine moiety in the 3,6-dihydro-2//-l,3-thiazine 149 on a-phthalimido acrylic acid affords the cyclic product 152, most probably through the intermediate 150. Support for the mechanisms comes from the isolation of the 5,6,7,8-tetrahydro-la//-thiireno[2,3-f]indolizine 151 in 10% yield (Scheme 10) <1999J(P1)3565>. 

Vilsmeier reaction, 4, 1051 Furo[3,2-6]pyrroles MO calculations, 6, 979 synthesis, 4, 1069 6, 1009 Furo[3,4-a]pyrrolo[2,1,5-cd]indolizine nomenclature, 1, 22 Furopyrylium salts, 4, 993-995 Furoquinolines biosynthesis, 4, 992 occurrence, 4, 988 pharmacology, 4, 992 reactions, 4, 988 synthesis, 4, 989 Furo[3,2-c]quinolines, 4, 991 Furo[3,4-fe]quinoxaline, 1,3-diphenyl-synthesis, 4, 993 Furoquinoxalines, 4, 992 Furo[2,3-6]quinoxalines synthesis, 4, 992 Furosemide toxicity, 1, 136 Furospinulosin UV spectra, 4, 587 Furospongin-I mass spectrometry, 4, 583 Furo[3,4-d][l,2,3]triazole, 2,6-dihydro-synthesis, 6, 996 Furo[3,4 -d][ 1,2,3]triazoles synthesis, 6, 996 Furoxan, 4-amino-3-aryl-tautomerism, 6, 404 Furoxan, 4-amino-3-methyl-synthesis, 4, 414 Furoxan, 4-aryl-3-methyl-rearrangement, 6, 408 Furoxan, 3-aryl-4-nitro-synthesis, 6, 414 Furoxan, 4-benzoyl-3-methyl-oxime... 

If R is benzoyl or acetyl and R1 is phenyl, a dihydro product (43) is formed in over 90% yield. If R is H or phenyl, an indolizine (44) is the major product, and the ease of oxidation of 43 appears to depend on the nature of R1. For an electron-donating group such as />-anisyl, the oxidation occurs very rapidly. 

The 1,5-cyclization of ylids has been applied to the synthesis of several bridgehead N systems, including indolizines, by Japanese workers, notably Tamura s group.68-71 Thus 45a-c on treatment with potassium carbonate in ethanol gave an indolizine 46 in high yield no dihydro intermediate was isolated (Scheme 10).88,69... 

Basketter and Plunkett402 reacted isoquinolinium ylids (379-382) with DMAD and isolated the 2,3-dihydrobenzo[g]indolizines 386-389 as well as the expected benzo[g]indolizines 383-385. Addition of MP to 379-382 gave the benzoindolizines but no dihydro compounds. Subsequently,403 these same workers reported an anomalous product 390 from 380 with DMAD in methanol. Japanese investigators have described very similar work.404-407... 

C. Schommer, Neue Synthese fur photochrome Dihydro(aza)indolizine, Thesis, Universitat des Saarlandes, Saarbriicken (1987). 

The attacks of heterocyclic A -oxides, e.g. of pyridine, quinoline, isoquinoline, phenanthridine, etc., on activated alkynes (RC CR R = R = COOMe R = Ph, R = COOEt R = Ph, R = CN) pose similar problems . An acyclic intermediate has been postulated but is rarely detected. Some of the possibilities are illustrated in equation (126) . If the open intermediate is formed, then the paths to the ylid and the 2-substituted quinoline in equation (126) seem simple enough, but several possible mechanisms can lead to the 3-substituted products . Other workers regard the reaction of the nitrone (or azomethine oxide) with alkyne as simple cycloadditions - which yield 2,3-dihydro-l,2-oxazoles since these are often unstable, only decomposition products may be found (equation 127). The construction of the indolizine skeleton initiated by a similar process has been reviewed (equation 128). ... 

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