Synthesis of Stable Derivatives of Cycloprop-2-ene Carboxylic Acid

Abstract

Large scale syntheses of 3-(cycloprop-2-en-1-oyl)-oxazolidinones from acetylene and ethyl diazoacetate are described. Unlike other cyclopropenes that bear a single substitutent at C-3, these compounds are stable to longterm storage. Although the cyclopropene derivatives are unusually stable, they are reactive toward cyclic and acyclic dienes in stereoselective Diels-Alder reactions.The Rh-catalyzed reaction of α-diazoesters with alkynes (Scheme 1) is an exceptionally useful and operationally simple method for the preparation of cycloprop-2-ene carboxylates 1 -substances that are useful building blocks for a number of strain-assisted transformations. 2 In theory, the Rh-catalyzed reaction of acetylene with ethyl diazoacetate should provide a particularly inexpensive route to ethyl cycloprop-2-ene carboxylate (1a). 3 Compound 1a and derivatives might serve as useful tools for diastereoselective synthesis. However, the usefulness of cyclopropenes with a single substituent at their sp 3 centers has been limited by their instability. Thus, 3-methylcyclopropene is extremely unstable, whereas 3,3-dimethylcyclopropene is quite stable at room temperature. 4 Although cycloprop-2-ene carboxylates (1) are more stable than 3-alkylcyclopropenes, their longterm storage is also not practical. 3a Herein, we describe scalable syntheses of 3-(cycloprop-2-en-1-oyl)-oxazolidinone derivatives 2-4: crystalline derivatives of cycloprop-2-ene carboxylic acid that are stable over long periods. Although derivatives 2-4 are unusually stable, they are reactive dienophiles that undergo Diels-Alder reactions with high stereoselectivity.Several preparations of cycloprop-2-ene carboxylates have been described in the literature. 3 In an important study, Baldwin and Villerica compared several routes to cycloprop-2-ene-1-carboxylates, and described a scalable, Rh-catalyzed procedure for the preparation of methyl cycloprop-2-ene carboxylate (1b). 3a Despite the considerable merits of the procedure, there were two limitations that detracted from the preparative utility: the need to prepare methyl

Live‐Cell Imaging of Cyclopropene Tags with Fluorogenic Tetrazine Cycloadditions

“…These dienophiles reacted very rapidly with monoaryl tetrazines, but the substituted cyclopropenes proved to be highly unstable and could not be stored overnight at −20 °C without degradation. Recently, Fox and co‐workers have elegantly demonstrated that N ‐acyloxazolidinone derivatives of cycloprop‐2‐enecarboxylic acid are unusually stable and therefore valuable cyclopropene synthons 15. Unfortunately, these modifications require a significant increase in the size of the reactive moiety and would defeat the purpose of using a small cyclopropene tag.…”

Halocycloalkenones as Diels–Alder Dienophiles. Applications to Generating Useful Structural Patterns

“…Following exposure to base, ring contraction would provide compounds of the type 25 , which is formally the product of a DA cycloaddition with the cyclopropene acid 26 . 14 In the forward direction, monobromoketene 15 was generated in situ , and underwent [2+2] cycloaddition with ethoxyacetylene 27 to provide the strained vinylogous ester 29 . Following some early setbacks, it was found that DIBAL-H cleanly reduces the ketone to allylic alcohol 30 , which could be unraveled in the presence of a small amount of BF 3 •OEt 2 to furnish 4-bromocyclobutenone 23 as a solution in CDCl 3 .…”

Acetylene and Ethylene: Universal C2 Molecular Units in Cycloaddition Reactions

“…2b However, the obtained cyclopropenes are unstable in any case and should be converted into other suitable building blocks. 36 Scheme 7. Rh-catalyzed methyl diazoacetate decomposition followed by cyclopropenation.…”