Condensed Pyridazines. VIII. Reaction of Diazolopyridazines with Ynamine. Formation of Benzodiazoles and Diazolodiazocines.

Oishi, Etsuo; Taido, N.; Miyashita, Akira; Satô, Susumu; Ohta, S.; Ishida, Hideyuki; Tanji, Ken‐ichi; Higashino, Takeo

doi:10.1248/cpb.39.1713

Cited by 6 publications

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“…Higashino and coworkers reported that substituted 1,2-diazines with ynamines were shown to proceed both [2+2] cycloaddition and [4+2] IEDDA cycloaddition, the [2+2] adduct followed with ring expansion to give diazacyclooctatetraene derivatives. They obtained [4+2] IEDDA product and diazacyclooctatetraene derivatives with comparable yield 12 , 13 However, these schemes were limited by high reaction barrier and low chemo-selectivity 14 . To best our knowledge, there remains no report of [2+2] cycloaddition pathway which can exceed [4+2] Diels–Alder pathway to produce IEDDA products so far.…”

Section: Introductionmentioning

confidence: 99%

Silylium ion mediated 2+2 cycloaddition leads to 4+2 Diels-Alder reaction products

Wang

Fan

2020

Commun Chem

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The mechanism of silver(I) and copper(I) catalyzed cycloaddition between 1,2-diazines and siloxy alkynes remains controversial. Here we explore the mechanism of this reaction with density functional theory. Our calculations show that the reaction takes place through a metal (Ag+, Cu+) catalyzed [2+2] cycloaddition pathway and the migration of a silylium ion [triisopropylsilyl ion (TIPS+)] further controls the reconstruction of four-member ring to give the final product. The lower barrier of this silylium ion mediated [2+2] cycloaddition mechanism (SMC) indicates that well-controlled [2+2] cycloaddition can obtain some poorly-accessible IEDDA (inverse-electron demand Diels-Alder reaction) products. Strong interaction of d10 metals (Ag+, Cu+) and alkenes activates the high acidity silylium ion (TIPS+) in situ. This п-acid (Ag+, Cu+) and hard acid (TIPS+) exchange scheme will be instructive in silylium ion chemistry. Our calculations not only provide a scheme to design IEDDA catalysts but also imply a concise way to synthesise 1,2-dinitrogen substituted cyclooctatetraenes (1,2-NCOTs).

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Section: Introductionmentioning

confidence: 99%

Silylium ion mediated 2+2 cycloaddition leads to 4+2 Diels-Alder reaction products

Wang

Fan

2020

Commun Chem

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The Retro–Diels–Alder Reaction PartII. Dienophiles with One or More Heteroatom

Rickborn

1998

Organic Reactions

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This review (Part II) is topically organized around the dienophile that is generated in a retro [4 + 2] reaction, and to the extent possible follows the principles adopted for Part I, which covers reactions in which both dienophile bonding centers are carbon atoms. The present chapter encompasses retro–Diels–Alder (rDA) reactions in which one or both of the dienophile reaction centers are heteroatoms. Any of the other atoms in the starting material (cycloadduct) may be carbon or heteroatom. Substituents on all positions are encompassed, and any bond order available to any oxidation state of an element is included, as is bonding to non‐nearest neighbor atoms (e.g., bicyclics). The reader is directed to Part I (Vol. 52) for general discussion of the rDA reaction, the features that affect rates and outcome, and the use of acids, bases, other catalysts, and scavengers. Certain subclassifications (e.g., processes proposed under MS conditions, polymer applications) of rDA reactions have been omitted from both sections; these topics are listed in the Introduction to Part I. Citations to over 100 reviews on various aspects of the rDA reaction are collected at the beginning of the References to Part I. Those that are especially pertinent to Part II will be repeated here, in the context of the particular dienophile under discussion. The decision to split the review of the rDA reaction into two parts was based on the volume of literature encountered, as outlined in the Introduction to Part I. Active literature searching was concluded for both Parts in April 1995, although occasional more recent references have been included.

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[2+2+2] Cycloadditions of Siloxy Alkynes with 1,2‐Diazines: From Reaction Discovery to Identification of an Antiglycolytic Chemotype

Montavon¹,

Türkmen²,

Shamsi³

et al. 2013

Angewandte Chemie

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The synthesis of new nitrogen-containing heterocycles plays a pivotal role in chemical biology and medicinal chemistry, as reflected by their many applications in the development of pharmacological probes and drugs. [1] Despite notable progress, there is a significant need for the identification of new nitrogen heterocycles which target previously unexplored regions of biogenic chemical space. Among the many possible synthetic strategies to such compounds, cycloadditions involving C-N multiple bonds are particularly attractive as they generate complex cyclic products by simultaneous formation of multiple bonds starting from readily available precursors. [2] Herein, we describe the discovery and development of a formal [2+2+2] cycloaddition of siloxy alkynes with phthalazines, a process that had not been previously described for either 1,2-diazines or electron-rich alkynes. [3][4][5][6][7] This effort has not only afforded heterocyclic products with a unique pentacyclic ring system but has also enabled the identification of a novel chemotype that inhibits glycolytic ATP production by direct blockage of glucose uptake in CHO-K1 cells. As a result of the prevalence of the Warburg effect in many human cancers, such compounds may prove useful in the development of new therapeutics which target reprogrammed energy metabolism of rapidly proliferating cells. [8] Our study began by examining the reaction of phthalazine (1) with the siloxy alkyne 2 in the presence of common Brønsted acids. While no reaction between 1 and 2 was observed in the absence of such additives, even at elevated temperatures, we found that addition of simple pyridinium salts promoted the formation of a new pentacyclic product (3; Scheme 1).After examining a range of mono-and bis(pyridinium) salts in various solvents, we determined the optimum protocol to entail the use of a stoichiometric amount of pyridinium trifluoromethanesulfonimide in CH 2 Cl 2 at room temperature, thus producing the lactam 3 as a single diastereomer in 77 % yield. While most of the known [2+2+2] cycloadditions typically require the presence of a transition-metal catalyst, [9] the present method promotes the condensation under remarkably mild reaction conditions, using only a simple, weak Brønsted acid. The excellent diastereoselectivity of this transformation is also highly noteworthy. The atom connectivity within the reaction product was initially determined to be that in 3 and is based on extensive use of NMR spectroscopic methods. Ultimately, the structure was secured and the relative stereochemistry of the three newly created stereogenic centers was defined through X-ray crystallographic analysis (see below).Interestingly, while a range of substituted mono-and bis(pyridinium) trifluoromethanesulfonimides were found to be effective as reaction promoters, the use of only HNTf 2 , in the absence of pyridine, produced 3 with lower efficiency (48 % yield) and diminished diastereoselectivity (83:17). Furthermore, the use of either pyridinium chloride, pyridinium p-toluenesulfo...

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Condensed Pyridazines. VIII. Reaction of Diazolopyridazines with Ynamine. Formation of Benzodiazoles and Diazolodiazocines.

Cited by 6 publications

References 0 publications

Silylium ion mediated 2+2 cycloaddition leads to 4+2 Diels-Alder reaction products

Silylium ion mediated 2+2 cycloaddition leads to 4+2 Diels-Alder reaction products

The Retro–Diels–Alder Reaction PartII. Dienophiles with One or More Heteroatom

[2+2+2] Cycloadditions of Siloxy Alkynes with 1,2‐Diazines: From Reaction Discovery to Identification of an Antiglycolytic Chemotype

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