Catalytic Ring Expansion of Vinyl Oxetanes: Asymmetric Synthesis of Dihydropyrans Using Chiral Counterion Catalysis

Abstract

As a part of our program aimed at developing new ringexpansion reactions from strained heterocyclic precursors [1] we are exploring vinyl oxetanes as potential candidates. We were particularly eager to learn if our success with the ring expansion of vinyl oxiranes to 2,5-dihydrofurans using [Cu-(hfacac) 2 ] could be translated into an equivalent transformation for vinyl oxetanes (Scheme 1). Given the allylic nature of the system and the favorable release of strain energy, vinyl oxetanes seemed like perfect ring-expansion candidates. Furthermore, we predicted that a broader range of catalysts would be competent for this new ring-expansion reaction because the competing 1,2-hydride shift pathway we needed to overcome for the vinyl oxirane ring expansion is less likely to occur for the vinyl oxetanes.In general, vinyl oxetanes have received limited attention, where the few published studies have focused on nucleophilic ring openings [2] of vinyl oxetanes and insertions of heteroatoms [3] into the oxetane. [4] There is only one report in the literature of a related lactonic vinyl oxetane ring expansion (Scheme 1). In 2000, when trying to expand the scope of their cationic-palladium-mediated b-lactone synthesis to include conjugated aldehydes Hattori et al. realized that in many cases d-lactones were formed. [5] The scope and yield of their cascade reaction, which was developed using classic palladium chemistry and relies on a superior leaving group to that in our ether ring expansion, was reasonable but limited to a few enals; enones were found to be poor substrates.We selected vinyl oxetane 1 as our model substrate. It is readily accessible by a nucleophilic addition to a commercially available b-chloro carbonyl precursor [6] and it has a phenyl group that we postulated would aid oxetane bond breaking and stabilization of a cationic intermediate. When 1 was subjected to the standard catalytic [Cu(hfacac) 2 ] conditions we used for the vinyl oxiranes, [1a] ring expansion to 3,6dihydro-2H-pyran 2 did indeed occur after prolonged heating at 150 8C, albeit in poor yield (Table 1, entry 1). The detrimental hydride shift pathway is presumably a far less likely competing path for vinyl oxetanes than vinyl oxiranes, therefore we decided to evaluate other stable readily available catalysts. Metal(II) triflates were the most effective catalysts and dichloromethane the best solvent. Copper(II) triflate (Table 1, entries 5-7) proved to be a remarkably wellsuited catalyst for the ring expansion, thus affording the desired product (2) both rapidly and quantitatively using only 1 mol % of catalyst at À78 8C. These results prompted us to Scheme 1. Proposed catalytic ring expansion of vinyl oxetanes. Table 1: Catalyst screening for vinyl oxetane ring expansion. Entry Catalyst mol % Solvent T [8C] t [h] % Conv.

Ring Expansions of Oxiranes and Oxetanes

“…Both monoand bis-stabilized diazo compounds were shown to be suitable substrates for the reaction. The Njardarson group reported a new catalytic vinyl oxetane ring expansion, which proceeded most favorably in the presence of Cu(II)(OTf) 2 , to form dihydropyran products in excellent yields (Scheme 43) [54]. This ring-expansion reaction was shown to also be catalyzed by Bronsted acids, which strongly suggested that the oxetane was converted into an allyl cation intermediate.…”

Synthesis and cationic ring‐opening polymerization of oxetane monomer containing five‐membered cyclic carbonate moiety via highly chemoselective addition of CO2

“…A rare type of functionalized 15‐membered macrocycles was prepared by the condensation of one molecule of α‐diazo‐β‐keto ester and three molecules of oxetane . Vinyloxetanes and alkynyloxetane undergo intramolecular ring‐expansion reactions to form 3,6‐dihydro‐ 2H ‐pyrans, 2,3‐dihydrofurans, and lactones . The ring‐opening reactions of oxetanes with stoichiometric amount of nucleophiles proceeded to give various alcohols such as aryl alkyl alcohols, γ‐amino alcohols, hydroperoxy alcohols, dialkylperoxy alcohols, chiral alcohols, and so on .…”

Pd‐Catalyzed Enantioselective [6+4] Cycloaddition of Vinyl Oxetanes with Azadienes to Access Ten‐Membered Heterocycles

“…Only afew examples of ring opening allylic substitution to deliver achiral products have been documented (Scheme 1a pathway A). [6] Such an interesting transformation, however, would represent acompeting,intramolecular side reaction for the intermolecular cycloaddition. [5] In addition to these examples,aring expansion of vinyl oxetanes to prepare dihydropyrans was also reported (pathway C).…”