Propargyl Hydrazides: Synthesis and Conversion Into Pyrazoles Through Hydroamination

Yoshimatsu, Mitsuhiro; Ohta, Keizo; Takahashi, Nami

doi:10.1002/chem.201202828

Cited by 44 publications

(25 citation statements)

References 73 publications

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“…We were delighted to find that Y(OTf) 3 could promote the reaction ( Table 1, entry 2). Other rare earth metal salts, such as Yb(OTf) 3 , La(OTf) 3 , and Sc(OTf) 3 , also worked for this reaction, albeit with lower yields ( Table 1, entries [3][4][5]. For the catalyst of Yb(OTf) 3 , much more byproducts were generated which made the product purification more difficult.…”

Section: Letter Syn Lettmentioning

confidence: 97%

Y(OTf)3-Catalyzed Cascade Propargylic Substitution/Aza-Meyer–Schuster Rearrangement: Stereoselective Synthesis of α,β-Unsaturated Hydrazones and Their Conversion into Pyrazoles

Liu

Wang

Zhao

et al. 2015

Synlett

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through a cascade propargylic substitution/aza-Meyer-Schuster rearrangement 29 examples high stereoselectivity R 1Abstract A straightforward and concise method for the highly stereoselective synthesis of α,β-unsaturated hydrazones by the Y(OTf) 3 -catalyzed cascade propargylic substitution/aza-Meyer-Schuster rearrangement reaction of tertiary propargylic alcohols and p-toluenesulfonyl hydrazide under an air atmosphere is developed. A series of α,β-unsaturated hydrazones have been synthesized from simple and readily available starting materials in good yields. Furthermore, the obtained α,β-unsaturated hydrazones are converted into pyrazoles in the presence of LiOt-Bu.Keywords propargylic alcohols, aza-Meyer-Schuster rearrangement, Y(OTf) 3 , α,β-unsaturated hydrazones, pyrazoles Currently, considerable interest has been focused on the transition-metal-catalyzed cascade reactions of propargylic alcohols, since these novel reactions can directly construct diverse complicated organic molecules from readily available starting materials under very mild conditions. 1 Among these, the Lewis acid catalyzed carbon-carbon and carbonheteroatom bond formations of propargylic alcohols with various nucleophiles have been extensively investigated over the last few decades. 2 However, compared to the wide applications of amine nucleophiles in the C-N bond formation reactions of propargylic alcohols, particularly tertiary propargylic alcohols, the use of hydrazines as nucleophiles is barely documented. 3 In 2012, Yoshimatsu and co-workers reported the first convenient method for the preparation of propargyl hydrazides from tertiary propargylic alcohols through scandium-catalyzed hydrazination in MeNO 2 -H 2 O (Scheme 1, eq 1). 4 Almost at the same time, Zhan and coworkers reported a novel FeCl 3 -catalyzed domino regioselective propargylic substitution/aza-Meyer-Schuster rearrangement reaction for the synthesis of acrylonitriles from trimethylsilyl-substituted tertiary propargylic alcohols and p-toluenesulfonyl hydrazide (Scheme 1, eq 2). 5 More recently, the same group has also developed a one-pot synthesis of pyrazoles from tertiary propargylic alcohols and ptoluenesulfonyl hydrazide through a two-step cascade sequence (Scheme 1, eq 3). 6 During our recent studies on propargylic chemistry, 7 we have found that tertiary propargylic alcohols with p-toluenesulfonyl hydrazide can be efficiently converted into α,β-unsaturated hydrazones using Y(OTf) 3 [yttrium(III) tifluoromethanesulfonate] as the catalyst through a cascade propargylic substitution/aza-MeyerSchuster rearrangement reaction (Scheme 1, eq 4). Moreover, the obtained α,β-unsaturated hydrazones can be further transformed into pyrazoles in the presence of LiOt-Bu. Herein we report the results of this study. Scheme 1 The reactions of tertiary propargylic alcohols with p-toluenesulfonyl hydrazide (1) (2) (3) (4) this work R 1 OH R 3 R 2 + TsNHNH 2 R 1 R 3 R 2 NNHTs Y(OTf) 3 (20 mol%) MeCN, 80 °C R 1 OH TMS R 2 + TsNHNH 2 FeCl 3 (10 mol%) MeNO 2 , 60 °C R 2 R 1 CN R 1 OH R 3 R...

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Section: Letter Syn Lettmentioning

confidence: 97%

Y(OTf)3-Catalyzed Cascade Propargylic Substitution/Aza-Meyer–Schuster Rearrangement: Stereoselective Synthesis of α,β-Unsaturated Hydrazones and Their Conversion into Pyrazoles

Liu

Wang

Zhao

et al. 2015

Synlett

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“…Elemental analyses were performed at the Center of Instrumentation of Gifu University. All propargyl hydrazines 1–12 were prepared using previously established procedures …”

Section: Methodsmentioning

confidence: 99%

“…3,5‐Diphenyl‐1 H ‐pyrazole (30): Sodium hydride (42 mg, 0.10 mmol) was added to a DMF (1.0 mL) solution of cyanomethyl‐2‐(1,3‐diphenylprop‐2‐yn‐1‐yl)‐ p ‐tolylsulfonylhydrazine ( 13c ) (42 g, 0.10 mmol) at 0 °C. The reaction mixture was stirred for 5 min and then poured into water (50 mL).…”

Section: Methodsmentioning

confidence: 99%

“…Recently, we reported the regioselective synthesis of pyrazoles from propargyl alcohols with tosylhydrazine via the corresponding hydrazides, which were isolated by our original procedure . Hydrazones have been reported to be a good tool for the synthesis of pyrazoles via intra and intermolecular cyclization reactions with alkynes,, cyclobutanones, and other substituted pyrazoles .…”

Section: Introductionmentioning

confidence: 99%

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Propargyl Hydrazides as Useful Intermediates Leading to Pyrazoles via Reaction with Certain Electrophiles

et al. 2016

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“…Moreover, propynal is not readily amenable to the common reductive amination strategies used to prepare N ′‐alkyl carbazates . Alkylations of carbazates, semicarbazones, and hydrazides with halides and alcohols have provided propargyl hydrazine derivatives but often require significant protection, and substituted propargyl alcohols …”

Section: Introductionmentioning

confidence: 99%

Aza‐propargylglycine installation by aza‐amino acylation: Synthesis and Ala‐scan of an azacyclopeptide CD36 modulator

et al. 2018

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Aza‐propargylglycine (azaPra) peptides are branching points for the synthesis of azapeptide libraries. Efficient alkylation of N‐(Fmoc)hydrazine in solution was found to provide N′‐propargyl fluorenylmethyl carbazate 13, which on activation gave N‐(Fmoc)‐azaPra acid chloride for installation into peptides. Reducing the number of steps on resin for azaPra peptide synthesis, which previously necessitated alkylation of a semicarbazone protected aza‐glycine residue, the new method offers potential for higher yield, as demonstrated by the synthesis of azacyclopeptide 1a, as well as by an alanine scan of this potent cluster of differentiation‐36 receptor (CD36) modulator.

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Propargyl Hydrazides: Synthesis and Conversion Into Pyrazoles Through Hydroamination

Cited by 44 publications

References 73 publications

Y(OTf)3-Catalyzed Cascade Propargylic Substitution/Aza-Meyer–Schuster Rearrangement: Stereoselective Synthesis of α,β-Unsaturated Hydrazones and Their Conversion into Pyrazoles

Y(OTf)3-Catalyzed Cascade Propargylic Substitution/Aza-Meyer–Schuster Rearrangement: Stereoselective Synthesis of α,β-Unsaturated Hydrazones and Their Conversion into Pyrazoles

Propargyl Hydrazides as Useful Intermediates Leading to Pyrazoles via Reaction with Certain Electrophiles

Aza‐propargylglycine installation by aza‐amino acylation: Synthesis and Ala‐scan of an azacyclopeptide CD36 modulator

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