Inter- and Intramolecular Addition/Cyclizations of Sulfonamide Anions with Alkynyliodonium Triflates. Synthesis of Dihydropyrrole, Pyrrole, Indole, and Tosylenamide Heterocycles

Feldman, Ken S.; Bruendl, Michelle M.; Schildknegt, Klaas; Bohnstedt, Adolph C.

doi:10.1021/jo9605814

Cited by 114 publications

(72 citation statements)

References 38 publications

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“…Initially we focused our attention on the reaction of metalated amides with alkynyl (phenyl)iodonium salts (eq 1). 9 Stang 10 and Feldman 11 have shown that this process provides an excellent route to "push-pull"-type ynamides (4, Z = COR, CO 2 R, SO 2 Ar, etc. ), and more recently Witulski and Rainier have extended this chemistry to the preparation of ynamides where Z = hydrogen, TMS, and phenyl.2a -d ,4b Unfortunately, this approach is not applicable to the synthesis of ynamides in which Z is a simple alkyl group.…”

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confidence: 99%

Copper-Mediated N-Alkynylation of Carbamates, Ureas, and Sulfonamides. A General Method for the Synthesis of Ynamides

2003

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A general amination strategy for the N-alkynylation of carbamates, sulfonamides, and chiral oxazolidinones and imidazolidinones is described. A variety of substituted ynamides are available by deprotonation of amides with KHMDS followed by reaction with CuI and an alkynyl bromide.We report herein a convenient and general method for the synthesis of ynamides via the copperpromoted coupling of amides with alkynyl bromides. Interest in the application of ynamides in organic synthesis has increased enormously in recent years.1 Considerably more robust than simple ynamines, ynamides are more easily stored and handled and tolerate a variety of conditions destructive to typical ynamines. Ynamides have thus emerged as versatile building blocks in a wide range of useful synthetic transformations including Pauson-Khand reactions, 2 ring-closing metatheses, 3 cycloadditions (and other ring-forming processes), 4 and a variety of hydrometalation and hydrohalogenation reactions. 5 , 6In connection with our studies on [4 + 2] cycloadditions of conjugated enynes7 and heteroenynes,8 we required an efficient method for the preparation of a wide range of ynamides, preferably via the direct alkynylation of carbamates, sulfonamides, and other simple amide derivatives. Initially we focused our attention on the reaction of metalated amides with alkynyl (phenyl)iodonium salts (eq 1). 9 Stang 10 and Feldman 11 have shown that this process provides an excellent route to "push-pull"-type ynamides (4, Z = COR, CO 2 R, SO 2 Ar, etc.), and more recently Witulski and Rainier have extended this chemistry to the preparation of ynamides where Z = hydrogen, TMS, and phenyl.2a-d ,4b Unfortunately, this approach is not applicable to the synthesis of ynamides in which Z is a simple alkyl group. The addition of soft nucleophiles to alkynyl(phenyl)iodonium salts is believed to proceed via the rearrangement of alkylidenecarbene intermediates of type 3, and the requisite 1,2-shift only is a facile process when Z is a hydrogen atom or trialkylsilyl or aryl group. 12 In addition, whereas sulfonamide derivatives (e.g., 1, EWG = Ts) participate smoothly in the desired transformation, reactions of lactams, 1a oxazolidinones, 1a and acyclic carbamates 13 proceed at best in low yield. NIH Public Access Author ManuscriptOrg Lett. Author manuscript; available in PMC 2010 July 6. The aforementioned limitations of alkynyl(phenyl)iodonium methodology prompted us to consider alternative and potentially more general approaches to the synthesis of the ynamides required for our studies. Recent developments in the laboratories of Buchwald and Hartwig have revolutionized methodology for carbon-nitrogen bond formation. 14 Encouraged, in particular, by Buchwald's recent success in achieving copper-catalyzed amidation of aryl halides,15 , 16 we turned our attention to the coupling of amide derivatives with readily available alkynyl halides. 17 Initial results were disappointing. Application of Buchwald's catalyst system 15 to the coupling of acyclic carbamates w...

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Copper-Mediated N-Alkynylation of Carbamates, Ureas, and Sulfonamides. A General Method for the Synthesis of Ynamides

2003

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“…However, an unanticipated result upon exploration of some routine indole formation chemistry provided the conceptual refocusing necessary to connect 2 to alkynyliodonium salt chemistry. 13 Exposure of tosylanilide (55) to base and then propynyl(phenyl)iodonium triflate furnished the expected indole product 57 via the presumed intermediacy of alkylidenecarbene 56. However, lesser amounts of a highly colored material whose spectral characterization led to the structural assignment 59 were identified as well.…”

Section: Methodsmentioning

confidence: 99%

Application of alkynyliodonium salts to natural products synthesis: A mini-review of recent work at Penn State

Feldman¹

2003

Arkivoc

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Total syntheses of the polycyclic natural products agelastatin A and pareitropone have been accomplished through the agency of alkynyliodonium salts. A review of these efforts, which emphasizes the value of hypervalent iodine chemistry in raising the molecular complexity of substrates upon chemical transformation, follows.Keywords: Agelastatin A, pareitropone, alkynyliodonium salts, natural products synthesis A desire to exploit the unique reactivity patterns offered by alkynyliodonium salts (5) has fueled a continuing effort to develop efficient syntheses of naturally occurring principles at Penn State. A progress report that details some recently completed projects in the areas of agelastatin A (1) and pareitropone (2) assembly is described herein.1 These advances owe much to the seminal contributions of many workers around the world, especially those recorded by the groups of Stang, Koser and Moriarity in the US, Ochiai and Kita in Japan, and, of course, by Anastasios Varvoglis' group at Thessaloniki. 2,3,4 In particular, this renaissance in hypervalent iodine chemistry is captured beautifully in two recent scholarly treatises authored by Varvoglis. 3 These books provide the foundation of, and the inspiration for, the synthesis work outlined below. Successful execution of total synthesis efforts often hinges on identifying solutions to problems of chemo-and stereoselectivity. Synthesis routes featuring alkynyliodonium salts are no exception, and key discoveries by Stang, 5 and independently, Ochiai, 6 have provided insight into how these types of selectivity issues might be addressed. In 1991, Stang and Zhdankin introduced PhI(CN)OTf (4) as a phenyliodonium transfer reagent of exquisite chemoselectivity in preparing alkynyliodonium units 5 from alkynylstannane precursors 3, Scheme 1. 5 Prior to this advance, it was unclear whether any of the existing iodonium transfer reagents could perform with the requisite selectivity that reaction with complex, multifunctional substrates demanded.

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“…The first example was reported by Stang and co-workers in 1994, but this transformation was limited to the synthesis of push-pull ynamines (Scheme 2.6, A [56]). An important breakthrough was reported by Feldman and co-workers [57] and Witulski and co-workers [58], who demonstrated that alkynyliodonium triflates could be used for the synthesis of more stable ynamides (Scheme 2.6, B). The first efficient synthesis of this fascinating class of compounds allowed their widespread use in organic synthesis, especially in metal-catalyzed cycloisomerization and cycloaddition reactions [59].…”

Section: Alkynylation Of Oxygen and Nitrogen Nucleophilesmentioning

confidence: 99%

Alkynylation with Hypervalent Iodine Reagents

Waser

2015

Topics in Current Chemistry

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Alkynes are among the most versatile functional groups in organic synthesis. They are also frequently used in chemical biology and materials science. Whereas alkynes are traditionally added as nucleophiles into organic molecules, hypervalent iodine reagents offer a unique opportunity for the development of electrophilic alkyne synthons. Since 1985, alkynyliodonium salts have been intensively used for the alkynylation of nucleophiles, in particular soft carbon nucleophiles and heteroatoms. They have made especially a strong impact in the synthesis of highly useful ynamides. Nevertheless, their use has been limited by their instability. Since 2009, more stable ethynylbenziodoxol(on)e (EBX) reagents have been discovered as superior electrophilic alkyne synthons in many transformations. They can be used for the alkynylation of acidic C-H bonds with bases or aromatic C-H bonds using transition metal catalysts. They were also highly successful for the functionalization of radicals or transition metal-catalyzed domino processes. Finally, they allowed the alkynylation of a further range of heteroatom nucleophiles, especially thiols, under exceptionally mild conditions. With these recent discoveries, hypervalent iodine reagents have definitively demonstrated their utility for the efficient synthesis of alkynes based on non-classical disconnections.

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Inter- and Intramolecular Addition/Cyclizations of Sulfonamide Anions with Alkynyliodonium Triflates. Synthesis of Dihydropyrrole, Pyrrole, Indole, and Tosylenamide Heterocycles

Cited by 114 publications

References 38 publications

Copper-Mediated N-Alkynylation of Carbamates, Ureas, and Sulfonamides. A General Method for the Synthesis of Ynamides

Copper-Mediated N-Alkynylation of Carbamates, Ureas, and Sulfonamides. A General Method for the Synthesis of Ynamides

Application of alkynyliodonium salts to natural products synthesis: A mini-review of recent work at Penn State

Alkynylation with Hypervalent Iodine Reagents

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