Application of the Pummerer Reaction Toward the Synthesis of Complex Carbocycles and Heterocycles

Padwa, Albert; Gunn, David; Osterhout, Martin H.

doi:10.1055/s-1997-1384

Cited by 144 publications

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“…27 Since the combination of a Pummerer/Mannich cyclization sequence offers unique opportunities for the assemblage of complex target molecules, 28 we decided to study the acid-induced cyclization of enamides 46 (n=1) and 47 (n=2) to determine whether these systems could also be used to assemble the core skeleton of the erythrina/homoerythrina family of alkaloids. Furanyl azide 43 was easily converted into the desired enamide sulfide (i.e., 44) following the azide/iminophosphorane/ethylthioacetyl chloride protocol already established (Scheme 10).…”

Section: Resultsmentioning

confidence: 99%

Acid-Promoted Cyclization Reactions of Tetrahydroindolinones. Model Studies for Possible Application in a Synthesis of Selaginoidine

et al. 2006

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The synthesis of various substituted bicyclic lactams by an acid-induced Pictet-Spengler reaction of tetrahydroindolinones bearing tethered heteroaromatic rings is presented. The outcome of the cyclization depends on the position of the furan tether, tether length, nature of the tethered heteroaromatic ring and the substituent group present on the 5-position of the tethered heteroaryl group. A one-pot procedure was developed to efficiently prepare tetrahydroindolinones containing tethered furan rings. In a typical example, the reaction of furanyl azide 26 with n-Bu 3 P delivered iminophosphorane 27, which was allowed to react with a 1 -alkyl-(2-oxocyclohexyl)acetic acid to provide the desired furanyl substituted tetrahydroindolinone system 29. Treatment of 29 with trifluoroacetic acid afforded the tetracyclic lactam skeleton 30 found in the alkaloid (±)-selaginoidine.

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Section: Resultsmentioning

confidence: 99%

Acid-Promoted Cyclization Reactions of Tetrahydroindolinones. Model Studies for Possible Application in a Synthesis of Selaginoidine

et al. 2006

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“…The mechanism of this reaction is presumed to be the Pummerer-type reaction [26][27][28] as shown in Chart 4. At first, the reaction of the sulfoxide 3 with TFAA gives an acyloxysulfonium ion A.…”

Section: Chartmentioning

confidence: 99%

A New Synthesis of 2-Sulfanyl Allylic Alcohols and .ALPHA.-Sulfanyl Ketones from Carbonyl Compounds and 1-Chloroalkyl p-Tolyl Sulfoxides with Carbon-Carbon Bond-Formation

Satoh

Takahashi

Shirai

et al. 2006

CHEMICAL & PHARMACEUTICAL BULLETIN

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Organosulfur compounds are very valuable in organic synthesis and innumerable studies for their chemistry and applications in organic synthesis have been reported. [1][2][3][4][5][6] Especially, sulfoxides have a variety of reactivity and are most extensively used in organic synthesis. [7][8][9] We also have long been interested in the organosulfur compounds in organic synthesis. We recently focused our attention on 1-chloroalkyl aryl sulfoxides as useful compounds in organic synthesis, many novel synthetic methods of which have appeared. [10][11][12][13][14][15][16][17][18][19][20] In continuation of our interest in the use of 1-chloroalkyl aryl sulfoxides in organic synthesis, we recently treated the achloro-b-hydroxy sulfoxides, which were synthesized from carbonyl compounds and 1-chloroalkyl p-tolyl sulfoxide, with trifluoroacetic anhydride (TFAA) in the presence of NaI, and quite interesting results were obtained (Chart 1).Thus, addition reaction of lithium a-sulfinyl carbanion of 1-chloroalkyl p-tolyl sulfoxides 2 to carbonyl compounds 1 gave adducts, b-hydroxy sulfoxides 3, in high to quantitative yields. The adducts 3 were treated with TFAA and NaI in acetone at 0°C to give 2-sulfanylated allylic alcohols 4 in high to quantitative yields. On the other hand, the adducts derived from aldehydes (3, R 2 ϭH) were treated with TFAANaI to give a-sulfanylated ketones 5 and/or the allylic alcohols 4, depending on the substituents on the adducts 3, in good to high yields. These products, 4 and 5, are quite important compounds in organic synthesis. Details of this procedure and the reaction mechanisms are discussed.A representative example of the reaction is described as follows (Chart 2). Thus, treatment of 1-chloroalkyl p-tolyl sulfoxide 2a 13) with slight excess of LDA in THF at Ϫ78°C resulted in the formation of lithium a-sulfinyl carbanion. To this reaction mixture was added cyclohexanone to afford the adduct 3a in 91% yield as a single product. The adduct 3a was next treated with excess TFAA in the presence of NaI in acetone at 0°C for 10 min. 21,22) A quite clean reaction took place and the product was found to have a hydroxyl group and one vinylic hydrogen and the structure was found to be the allylic alcohol having a sulfanyl group 4a.Obviously, this reaction was recognized to be a very interesting method for synthesis of allylic alcohols having a sul- Ichigaya-Funagawara-machi, Shinjuku-ku, Tokyo 162-0826, Japan. Received July 21, 2006; accepted September 6, 2006 Reaction of lithium a a-sulfinyl carbanions of 1-chloroalkyl p-tolyl sulfoxides with ketones or aldehydes at low temperature gave adducts in almost quantitative yields. Treatment of the adducts derived from ketones with trifluoroacetic anhydride (TFAA) in the presence of NaI in acetone gave a a-sulfanyl allylic alcohols in good to quantitative yields. On the other hand, treatment of the adducts derived from aldehydes with TFAA and NaI resulted in the formation of a a-sulfanyl ketones and/or a a-sulfanyl allylic alcohols. These reactions offe...

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“…As a prerequisite for an ideally proceeding one-pot sequential transformation, the reactivity pattern of all participating components has to be such, that each building block gets involved in a reaction only when it is supposed to do so. The development of sequences that combine transformations of differing fundamental mechanism broadens the scope of such procedures in synthetic chemistry [22][23][24][25][26][27][28][29][30][31][32][33][34].…”

Section: Introductionmentioning

confidence: 99%

Tandem Methodology for Heterocyclic Synthesis

Padwa

2005

ChemInform

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Tandem methodology for heterocyclic synthesis represents a powerful approach for the rapid buildup of molecular complexity from potentially simple starting materials. Work from our laboratory has shown that the rhodium(II)-catalyzed cyclization cascade of α-diazo imides represents an effective method for the synthesis of a variety of heterocyclic systems. As an extension of these studies, we became interested in using a linked Pummerer/N-acyliminium ion cyclization sequence since we felt that this combination offers unique opportunities for the assemblage of complex target molecules. A synthetic method that combines transformations of different reaction types significantly broadens the scope of such procedures in synthetic chemistry. α-Thiocarbocations generated from the Pummerer reaction of β-phenylsulfinylmethyl-α,β-unsaturated amides can be intercepted by the adjacent amido group to produce transient amino-substituted furans which undergo subsequent Diels-Alder cycloadditions. Using this domino amido Pummerer/Diels-Alder cascade, we were able to assemble novel polycyclic systems in a single operation. The key step in the process involves the generation of a reactive N-acyliminium ion by fragmentation of an amino-substituted [4+2]-cycloadduct. The successful synthesis of a number of alkaloids by this sequence of reactions reveals the usefulness and importance of this unique domino cascade. Application of the process for the preparation of the stenoma alkaloid stenine was recently carried out in our laboratory.

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Application of the Pummerer Reaction Toward the Synthesis of Complex Carbocycles and Heterocycles

Cited by 144 publications

References 0 publications

Acid-Promoted Cyclization Reactions of Tetrahydroindolinones. Model Studies for Possible Application in a Synthesis of Selaginoidine

Acid-Promoted Cyclization Reactions of Tetrahydroindolinones. Model Studies for Possible Application in a Synthesis of Selaginoidine

A New Synthesis of 2-Sulfanyl Allylic Alcohols and .ALPHA.-Sulfanyl Ketones from Carbonyl Compounds and 1-Chloroalkyl p-Tolyl Sulfoxides with Carbon-Carbon Bond-Formation

Tandem Methodology for Heterocyclic Synthesis

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