Elsevier

Tetrahedron

Volume 75, Issue 31, 2 August 2019, Pages 4071-4080
Tetrahedron

Brønsted acid−catalyzed synthesis of tetrasubstituted allenes and polysubstituted 2H-chromenes from tertiary propargylic alcohols

https://doi.org/10.1016/j.tet.2019.05.023Get rights and content

Abstract

A practical and environmentally benign Brønsted acid−catalyzed protocol for the preparation of all-carbon tetrasubstituted allenes, consisting in the direct SNˈ addition of tri- or dimethoxy arenes or allyltrimethylsilane to tertiary propargylic alcohols, has been developed. In addition, a straightforward synthesis of densely substituted 2H-chromenes by metal-free tandem allenylation/heterocyclization reaction of methoxyphenols and tertiary alkynols is presented.

Introduction

Allenes are valuable building blocks with abundant applications in synthetic organic chemistry [1] or advanced material science [2] and commonly found in natural products and pharmacological active molecules [3]. So, the development of simple and efficient methods for the synthesis of allenes is an extremely active field in organic chemistry [4]. Among all the strategies described for the formation of the allene unit, the most extended and convenient method involves the nucleophilic substitution by organometallic species of acetylene derivatives bearing a leaving group at the propargylic carbon. This route turns to be almost unique for the synthesis of all-carbon tetrasubstituted allenes using metal catalysts derived from Cu, Rh, Pd, Mn, Ni or Fe and leaving groups such as halides, epoxides, sulfonates, phosphates, acetates or carbonates [5]. Moreover, the direct use of tertiary propargylic alcohols as substrates has been also extensively reported in the presence as catalysts of both Lewis acids [6] and late transition metals [7]. This route has the evident advantages of the wide availability and environmentally benign character of alcohols as well as the formation of water as the only byproduct of the process. However, these methods are limited by the precious, toxic, and/or moisture-sensitive nature of some of the catalysts employed.

In this scenario, the development of allenylation protocols using simple Brønsted acids as catalysts would be highly convenient. This approach implies the initial formation of an allenic-propargylic cation intermediate followed either by the nucleophilic substitution that could occur at both active positions or, alternatively, by a competitive elimination (Fig. 1). Thus, selective addition of the carbon nucleophile through a SNˈ mechanism is a key issue for the success of this strategy. Few efficient and general Brønsted acid-catalyzed syntheses of all-carbon tetrasubstituted allenes have been reported and they are restricted to the employment of 2-substituted indoles or 1,3-dicarbonyl compounds or related activated methylenes as nucleophiles [8,9].bib9

Based in our experience in the metal-free Brønsted acid-catalyzed direct nucleophilic substitutions of varied π-activated alcohols [8a-c], [9]a), [10], we envisioned that the combination of tertiary propargylic alcohols with bulky substituted electron-rich arenes would favored the SNˈ nucleophilic addition, thus allowing the synthesis of all-carbon tetrasubstituted allenes.

Section snippets

Results and discussion

To test the viability of the proposed synthesis of allenes, we first investigated the reaction between highly activated tertiary alkynol 1a and 1,3,5-trimethoxybenzene using p-toluenesulfonic acid (PTSA) as ready available and easily handled Brønsted acid catalyst. Pleasantly, the corresponding desired allene 2a was exclusively obtained in good yield and in short reaction time (30 min) when performing the reaction in MeCN at room temperature in an open vessel (Table 1, entry 1). As would be

Conclusions

In conclusion, we have developed a clean, simple and effective metal-free methodology for the preparation of functionalized all-carbon tetrasubstituted allenes by direct nucleophilic substitution reaction of tertiary propargylic alcohols with tri- or dimethoxyarenes and allyltrimethylsilane. While the scope of the reaction with allyltrimethylsilane seems to be limited, a wide variety of allenes have been prepared employing rich aromatic compounds as nucleophiles. In addition, the employment of

General methods

All common reagents, catalysts and solvents were obtained from commercial suppliers and used without any further purification. The starting alkynols 1 were synthesized by well established procedures consisting in the nucleophilic addition of the appropriate lithium acetylide to the corresponding ketone. All reactions were assembled under air atmosphere in oven-dried glassware with magnetic stirring. TLC analysis was performed on aluminium-backed plates coated with silica gel 60 (230–240 mesh)

Acknowledgments

We are grateful to the Junta de Castilla y León and FEDER (BU291P18) and Ministerio de Economía y Competitividad (MINECO) and FEDER (CTQ2016-75023-C2-1-P) for financial support. N.C.-L and N.V. respectively thank Ministerio de Educación Cultura y Deporte (MECD) and Junta de Castilla y León and FEDER for predoctoral contracts.

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