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

Abstract

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...

Trivalent Y3+ ionic sensor development based on (E)-Methyl-N′-nitrobenzylidene-benzenesulfonohydrazide (MNBBSH) derivatives modified with nafion matrix

“…5 . A similar interaction in perspective of yttrium complex formation has been reported in the previous studies 32 .

Figure 5 Possible mechanism of 2-MNBBSH-Y-complex formation.

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Recent Developments in the Meyer‐Schuster Rearrangement

“…Then, reaction with t ‐BuOLi in toluene at 80 °C gave the desired pyrazoles 293 or 294 depending upon the nature of the substituents R 1 and R 2 (Scheme 72). [128] A one‐pot transformation, starting from alkyne and aryl ketones, was also demonstrated.…”

Sulfonyl Hydrazides in Organic Synthesis: A Review of Recent Studies

“…The Meyer‐Schuster rearrangement is an effective isomerization, by a 1,3‐shift of propargyl alcohols to afford α , β ‐unsaturated ketones. Treatment of propargyl alcohols with TsNHNH 2 , followed by Y(OTf) 3 catalyst gave the α,β‐ unsaturated ketones (Eq. 74‐1) (Scheme ).…”