Elsevier

Tetrahedron

Volume 70, Issue 34, 26 August 2014, Pages 5038-5045
Tetrahedron

Synthesis of multi-functional alkenes via Wittig reaction with a new-type of phosphorus ylides

https://doi.org/10.1016/j.tet.2014.06.015Get rights and content

Abstract

A Bu3P-mediated mild and efficient synthesis of multi-functional alkenes has been described starting from substituted acrylate with aldehydes. In situ generated zwitterionic intermediates underwent proton-exchange to afford ylide intermediates, which were trapped by corresponding aldehydes providing the products in up to 92% yield with complete E-stereoselectivity. Further derivatization of the products was performed to furnish functional pyridazinones.

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An efficient synthesis of multi-functional alkenes has been described starting from commercially available starting materials. Phosphorus ylide is the key intermediate in this approach. A plausible mechanism has been proposed and the products were further converted to pyridazinone derivatives.

Introduction

Highly functionalized activated alkenes are widely used as building blocks for several organic syntheses including natural products and drugs.1 There are many well-known methodologies that can construct carbon–carbon double bonds, such as Julia–Lythgoe and Julia–Kocienski olefination reactions,2 Peterson reaction,3 Horner–Wadsworth–Emmons reaction,4 and metathesis.5 Discovered in 1953 by Georg Wittig, the Wittig reaction is one of the most powerful methods and it occupies a central position in the construction of carbon–carbon double bonds.6 Hence the development of synthetic strategies for the new types of Wittig reagents is needed to expand the scope of the reaction in organic chemistry.7

Recently we have described an efficient method for the synthesis of highly functionalized furan derivatives using ethyl 3-benzoylacrylate (1), Bu3P, and acid chlorides in the presence of triethylamine (Scheme 1).8 The reaction proceeds through an intramolecular Wittig reaction of the in situ generated ylide intermediate (I) from (II) to provide the corresponding furans.9

We envisage that, the resulting zwitterionic species (II), after the addition of Bu3P to 1 can undergo a proton-exchange reaction followed by trapping with suitable substrates (such as aldehydes) to form highly substituted alkenes, E-(benzoyl)ethyl cinnamate (3) (Scheme 1). Although few literature reports are available for the synthesis of alkylidene/arylidine-succinates, no such attempts have been made to synthesize E-(benzoyl)ethyl cinnamate (3) via trapping zwitterionic intermediates with aldehydes.10 Herein, we wish to report a highly stereoselective Wittig reaction for the synthesis of multi-functional alkenes 3 starting from tributylphosphine, the corresponding Michael acceptors 1 and various aldehydes (2) in a single step (Scheme 1).

Section snippets

Results and discussion

We started our initial studies with the Michael acceptor 1a (1.1 equiv), para-nitrobenzaldehyde (2a, 1 equiv), and Bu3P (1.1 equiv) in toluene. The reaction proceeded smoothly at room temperature within 0.5 h, furnishing the alkene adduct 3aa in 85% yield as single stereoisomer (Table 1, entry 1).11

The stereochemistry of 3aa was confirmed by X-ray analysis (Fig. 1).12 Then the scope of the Bu3P-mediated Wittig reaction of 1a was investigated using various aldehydes to synthesize

Conclusion

We have developed a highly stereoselective PBu3-mediated Wittig reaction between 3-benzoylacrylate and aldehydes as a facile synthetic protocol for trisubstituted multi-functional alkenes. Numerous aldehydes have been employed efficiently to afford E-(benzoyl)ethyl cinnamate (3) in one-pot step and mild reaction conditions. The key step of the reaction is the formation of phosphorus ylide (II), which is generated via different way from that of the traditional method.

Typical procedure for preparation of 3aaaw

A dry and nitrogen-flushed 10 mL Schlenk flask, equipped with a magnetic stirring bar and a septum, was charged with a solution of 2a (151.0 mg, 1 mmol) in anhydrous toluene (4.0 mL). 1a (214.9 μL, 1.1 equiv) and Bu3P (274.6 μL, 1.1 equiv) were added sequentially, and the resulting mixture was stirred for 30 min at room temperature. Thereafter, the solvent was removed by evaporation in vacuo. Purification by flash chromatography (ethyl acetate/hexanes: 1/8) furnished 3aa as yellow solid

Acknowledgements

The authors thank the Ministry of Science and Technology of the R.O.C., Taiwan (NSC 101-2113-M-003-001-MY3) and National Taiwan Normal University (NTNU 100-D-06) for financial support.

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Y.-L. Tsai and S. Syu made equal contributions to this work.

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