Cycloaddition of Arynes and Cyclic Enol Ethers as a Platform for Access to Stereochemically Defined 1,2‐Disubstituted Benzocyclobutenes

Abstract

Benzocyclobutenes (BCBs) are important entities in a multitude of areas, such as complex organic synthesis, materials and polymer chemistry, and electronics. Whereas reactions between arynes and ketene acetals have been well studied, reactions with cyclic enol ethers are unknown. A cis olefin geometry in cyclic enol ethers makes them well suited for formal [2 + 2] cycloaddition with arynes than for competing ene reactions, making them effective reactants. Reactions of 2,3-dihydrofuran, 2,3-dihydro-3H-pyran, 5-butyl-2,3-dihydrofuran, (S)-2-((benzyloxy)methyl)-2,3-dihydrofuran, and 1,4-dioxene with various arynes were successful. An advantage of the use of cyclic enol ethers is that despite the plausible intermediacy of zwitterionic intermediates, the products are limited to a cis ring junction. This can be exploited for potential access to stereochemically-defined 1,2-disubstituted BCBs. As a demonstration, ether ring cleavage with BBr3 provided trans-functionalized BCBs and displacement with azide then provided cis derivatives. DFT computations have been utilized to understand the structures of three arynes in relation to the cycloadditions and for a predictive evaluation of product ratios in two cases. A comparative evaluation of the HOMO energies of a related series of cyclic olefins has also been performed by DFT computations.

Synthesis of Uracil-Iodonium(III) Salts for Practical Utilization as Nucleobase Synthetic Modules

“…Thus, the reaction of 3an-OTs with N - tert -Butyl-phenyl nitrone 8 [34] afforded a [3 + 2] annulated product 9 (Equation 1). The cycloaddition of 3,4-dihydro-2 H -pyran 10 [35] as an alkynophile yielded the [2 + 2] annulated product 11 (Equation 2). When diphenyldiselenide 12 [36] was subjected to the reaction conditions, σ-bond insertion occurred and the 5,6-difunctionalized product 13 was obtained in a moderate yield (Equation (3)).…”

Alkyl Enol Ethers: Development in Intermolecular Organic Transformation

“…Furthermore, Lakshman and co‐workers also reported the [2+2] cycloaddition of cyclic enol ether with aryne, in situ generated from 85 . Reaction proceeds in the presence of CsF:18‐Cr‐6 (1 : 1) in acetonitrile as a solvent to give 1,2‐disubstituted benzocyclobutene with excellent yield (Scheme 30B) [51] …”

[2 + 2] Cycloaddition of o-Carboryne with Vinyl Ethers: Synthesis of Carborane-Fused Cyclobutanes

“…For cage C-functionalization, o -carboryne (1,2-C 2 B 10 H 10 ) serves as a useful synthon, enabling the functionalization of both cage carbon vertices at the same time with different reactivity patterns, including [5 + 2]/[4 + 2]/[3 + 2]/[2 + 2] − cycloaddition, ene reaction, , and X–H (X = C and N) bond insertion. , Among these, [2 + 2] cycloadditions are symmetry-forbidden in the usual suprafacial process, leading to a poor selectivity and low yields in the reaction of o -carboryne with allenes, styrenes, and thiophenes. ,,,, One of the possible ways to address these issues is to employ electron-donating-group-substituted olefins as these electron-rich olefins can promote stepwise reaction pathway, facilitating nonconcerted cycloaddition. ,, In this regard, we explored the reaction of 1-Li-2-OTf- o -C 2 B 10 H 10 with vinyl ethers, leading to the development of a useful synthetic route to carborane-fused cyclobutanes in very good yields. These results are reported in this article (Scheme ).…”