Synthesis of Alkynyl Ethers and Low-Temperature Sigmatropic Rearrangement of Allyl and Benzyl Alkynyl Ethers

Abstract

Abstractα-Alkoxy ketones 3 can be transformed into 1-alkynyl ethers 5 by a two-step procedure involving formation of the enol triflate or phosphate and base-induced elimination. Performing the same reaction sequence with allylic alcohols (R 2 OH, R 2 = allyl) furnishes instead γ,δ-unsaturated carboxylic acid derivatives 6, derived from [3,3]-sigmatropic rearrangement of the intermediate allyl alkynyl ethers at −78 °C and trapping of the subsequently formed ketene with nucleophiles (Nu-H). Benzyl alkynyl ether 5 (R 2 = benzyl) rearranges to indanone 7 upon heating to 60 °C.Electron-rich alkynes, such as ynamines and ynol ethers, are functional groups that possess significant potential in organic chemistry for the formation of carbon-carbon bonds. 1 The synthetic utility of ynamides has been considerably expanded recently, along with the development of new methods for their facile preparation from simple building blocks. 2 1-Alkynyl ethers, while possessing many of the reactivity features of ynamides, have been far less investigated due to the relatively few methods currently available for their synthesis. 3 In this letter we present a mild and efficient method for the synthesis of diverse 1-alkynyl ethers and demonstrate that a facile sigmatropic rearrangement of allyl and benzyl alkynyl ethers furnishes products containing new carbon-carbon bonds.We have previously shown that treatment of allyl-1,1-dichlorovinyl ethers with 2.2 equiv of n-butyllithium at −78 °C, followed by quenching of the reaction mixture with excess alcohol, leads to rearranged γ,δ-unsaturated esters in high yield. 4 The reaction possesses many of the characteristics of a sigmatropic process, both in terms of its stereospecificity and geometrical requirements. We have proposed that an initially generated allyl alkynyl ether intermediate undergoes a [3,3]-sigmatropic rearrangement either as a neutral or as a negatively charged species.Due to its reactivity toward a range of functional groups, the use of the nucleophilic base nBuLi to generate the key intermediate in this reaction may be viewed as a potential limitation. Furthermore, the preparation of the allyl-1,1-dichlorovinyl ether substrate via methylenation of an allylic formate ester requires the use of toxic carbon tetrachloride in combination with triphenylphosphine. Since terminal and internal alkynes have been previously prepared from ketones by treatment of the corresponding enol phosphates or triflates with a non-nucleophilic base, 5 we sought to investigate the preparation of 1-alkynyl ethers from α-alkoxy ketones via E2 elimination of the derived enol triflates or phosphates.Following the procedure of Muthusamy et. al., 6 treatment of a toluene solution of diazoacetophenone 1a and menthol with a catalytic amount (10 mol %) of indium triflate at room temperature furnished α-alkoxy ketone 3a in 91% yield (Scheme 1). Formation of the enol triflate was achieved by stirring 3a with LiHMDS at −78 °C for one hour, followed by quenching with PhNTf 2 in DMPU/THF (1:2) and warming to room ...

(Z)-Selective Enol Triflation of α-Alkoxyacetoaldehydes: Application to Synthesis of (Z)-Allylic Alcohols via Cross-Coupling Reaction and [1,2]-Wittig Rearrangement

“…2d,5 Chelation-controlled preparation of (Z)-vinyl triflates from α-alkoxy ketones also has been reported. 6 Recently, Cu-catalyzed electrophilic vinyl triflation of alkynes was reported to afford (Z)-triflates. 7 For preparation of vinyl triflates from aldehydes, a mixture of (Z)-and (E)-vinyl triflates was formed through the use of triflic anhydride (Tf 2 O) and 4-methyl-2,6-(di-t-butyl)pyridine (DTBMP).…”

Synthesis of Alkynes from Vinyl Triflates Using Tetrabutylammonium Fluoride

“…Several different procedures for conversion of vinyl triflates to alkynes have been reported; however, as with vinyl bromides, most of the triflates require strong bases and anhydrous conditions, [18][19][20][21][22][23][24] or prolonged heating with weak bases at elevated temperatures. [25][26][27] The TBAFinduced elimination of vinyl triflates is rare in the literature, and only two examples of its use were found.…”

Low temperature n-butyllithium-induced [3,3]-sigmatropic rearrangement/electrophile trapping reactions of allyl-1,1-dichlorovinyl ethers. Synthesis of β-, γ- and δ-lactones

“…2 In addition, we have shown that α–alkoxyketones are precursors of alkynyl ethers via treatment of the derived enol triflates or phosphates with potassium tert -butoxide or Schlosser’s base at −78°C. 3 This process provides an additional protocol for the preparation of highly substituted 1-alkynyl ethers that cannot be prepared directly by electrophile trapping of lithioalkynyl ether intermediates available from 1,1- and 1,2-dichlorovinyl ethers.…”

“…However, in situ generation of allyl-alkynyl ethers by treatment of the corresponding allyl enol triflates with KO t -Bu at −85°C, followed by quenching with alcohols, also produces the expected rearrangement products in good yields. 3,5 …”