Expanding the Strained Alkyne Toolbox: Generation and Utility of Oxygen-Containing Strained Alkynes

Abstract

We report synthetic methodology that permits access to two oxacyclic strained intermediates, the 4,5-benzofuranyne and the 3,4-oxacyclohexyne. In situ trapping of these intermediates affords an array of heterocyclic scaffolds by the formation of one or more new C-C or C-heteroatom bonds. Experimentally determined regioselectivities were consistent with predictions made using the distortion/interaction model and were also found to be greater compared to selectivities seen in the case of trapping experiments of the corresponding N-containing intermediates. These studies demonstrate the synthetic versatility of oxacyclic arynes and alkynes for the synthesis of functionalized heterocycles, while further expanding the scope of the distortion/interaction model. Moreover, these efforts underscore the value of harnessing strained heterocyclic intermediates as a unique approach to building polycyclic heteroatom-containing frameworks.

Facile Synthesis of Azetidine Nitrones and Diastereoselective Conversion into Densely Substituted Azetidines

“…Initial investigations into the functionalization of azetidine nitrones 4 focused on [3+ +2] cycloaddition reactivity to access fused-ring systems,and reduction to prepare saturated azetidines with defined relative stereochemistry. [20] As shown in Scheme 2A,a zetidine 4a smoothly underwent diastereoselective cycloadditions with n-butylallenoate and benzyne to form azetidine-fused isoxazoline 6 and benzisoxazoline 7, respectively. [21] As shown in Scheme 2B,reduction of 4a was achieved using NaBH 3 CN with high cis selectivity for N-hydroxyazetidine 8.I nc ontrast, dealkoxycarbonylation Table 1: Optimization of the 4p-electrocyclization of N-alkenylnitrones 3a and 3b for the synthesis of azetidine nitrones 4a and 4b.…”

Cyclic Alkyne Approach to Heteroatom-Containing Polycyclic Aromatic Hydrocarbon Scaffolds

“…Pyrone 13 a readily undergoes aD A/ rDAreaction sequence,with loss of CO 2 ,inthe presence of arynes or nonaromatic cyclic alkynes (generated from silyl triflate precursors 15)atambient temperature ( Figure 4). Cyclohexyne (23), and heterocyclic strained cyclic alkynes 25 [13] and 26 [16] performed smoothly (entries 4-6). Cyclic alkynes,which offer greater sp 3 -character and improved solubility of eventual products were also tested.…”

“…Cyclic alkynes,which offer greater sp 3 -character and improved solubility of eventual products were also tested. [6,13,16] We also sought to access products bearing differing C and D rings.A sn oted earlier, in most routes to 9,10-anthracene derivatives,t he C and D rings are introduced through ad ouble cross-coupling or by the double addition of an organometallic reagent, allowing for the formation of only symmetric products with limited functional group compatibility. [54] With regard to regioselectivities (entries 2, 5, and 6), the major product likely arises from initial bond formation occurring between the more electron-rich carbon adjacent to the carbonyl group of the pyrone [55] and the more distorted carbon of the strained intermediate in ac oncerted asynchronous fashion.…”

“…[1][2][3][4] Additionally,such efforts have led to ag reater understanding of aryne and cyclic alkyne reactivity and regioselectivities, [5][6][7] and ah ost of synthetic applications impacting catalysis, [8] agrochemistry, [9] pharmaceuticals,a nd academia. [12][13][14][15][16][17][18][19] One exciting application of arynes and cyclic alkynes lies in materials chemistry.A rynes have been employed in the synthesis of polymers and polycyclic aromatic hydrocarbons (PAHs), [2,[20][21][22][23] with the latter having aremarkable impact on the materials science field. [12][13][14][15][16][17][18][19] One exciting application of arynes and cyclic alkynes lies in materials chemistry.A rynes have been employed in the synthesis of polymers and polycyclic aromatic hydrocarbons (PAHs), [2,[20][21][22][23] with the latter having aremarkable impact on the materials science field.…”

Cyclic Alkyne Approach to Heteroatom-Containing Polycyclic Aromatic Hydrocarbon Scaffolds

“…[10,11] As election of important arynes and cyclic alkynes are shown in Figure 1. [12][13][14][15][16][17][18][19] One exciting application of arynes and cyclic alkynes lies in materials chemistry.A rynes have been employed in the synthesis of polymers and polycyclic aromatic hydrocarbons (PAHs), [2,[20][21][22][23] with the latter having aremarkable impact on the materials science field. [24,25] PA Hs have been used in widely-used devices,such as organic lightemitting diodes (OLEDs), field effect transistors (OFETs), and photovoltaics (OPVs).…”