Modular Synthesis of Unsymmetrical Doubly-ring-fused Benzene Derivatives Based on a Sequential Ring Construction Strategy Using Oxadiazinones as a Platform Molecule

Abstract

An efficient benzene ring construction method using oxadiazinones as a platform molecule has been developed. Sequential reactions of oxadiazinones with cycloalkynes and arynes afforded partially reduced polyaromatics. This method enables facile preparation of various unsymmetrical doublyring-fused benzene derivatives including multisubstituted tetrahydroanthracenes and anthracenes.

Cycloaddition Cascades of Strained Alkynes and Oxadiazinones

“…In an effort to favor the formation of benzopyrone 3 , we carried out the reaction of benzyne precursor 20 with a two‐fold excess of oxadiazinone 2 . In this instance we only observed double addition product 18 in a 33 % yield (Table 1, entry 1) and no evidence of benzopyrone 3 , consistent with previous observations [11, 15, 17, 18] . In contrast, when cyclohexyne precursor 21 was employed in the presence of 2 equivalents of oxadiazinone 2 , pyrone 16 was obtained in 75 % yield (Table 1, entry 2).…”

“…In an effort to favor the formation of benzopyrone 3,w ec arried out the reaction of benzyne precursor 20 with at wo-fold excess of oxadiazinone 2.I nt his instance we only observed double addition product 18 in a3 3% yield (Table 1, entry 1) and no evidence of benzopyrone 3,c onsistent with previous observations. [11,15,17,18] In contrast, when cyclohexyne precursor 21 was employed in the presence of 2equivalents of oxadiazinone 2,p yrone 16 was obtained in 75 %y ield (Table 1, entry 2). This observation provides the basis for accessing non-symmetric PA Hscaffolds via asecond DA/r-DAreaction sequence of pyrone 16 with as econd, distinct aryne or cyclic alkyne.R ecently,H osoya and co-workers demonstrated that the reaction of ac yclohexyne precursor and oxadiazinone 2 can lead to selective formation of alkylpyrone 16, [18] albeit using slightly different reaction conditions than those identified herein.…”

“…We also disclosed a one‐pot variant wherein strained alkyne 5 and aryne 8 are cogenerated in the presence of oxadiazinone 6 to give tricyclic scaffolds 9 directly. Of note, Hosoya and co‐workers recently demonstrated the use of 1,2‐cyclohexyne in this methodology [18] . Altogether, the DA/r‐DA cascades of cyclic alkynes and arynes allow rapid access to PAH scaffolds with promising applications.…”

“…Altogether, the DA/r‐DA cascades of cyclic alkynes and arynes allow rapid access to PAH scaffolds with promising applications. For example, compounds 10 – 13 demonstrate the promise of this methodology for accessing organic semiconductors, [13] stimuli‐responsive materials, [17] biorthogonal labeling tools, [18] and donor–acceptor polymers (Figure 1 c). [17] …”

“…We also disclosed ao ne-pot variant wherein strained alkyne 5 and aryne 8 are cogenerated in the presence of oxadiazinone 6 to give tricyclic scaffolds 9 directly.O fn ote,H osoya and co-workers recently demonstrated the use of 1,2-cyclohexyne in this methodology. [18] Altogether,t he DA/r-DAc ascades of cyclic alkynes and arynes allow rapid access to PA Hs caffolds with promising applications.For example,compounds 10-13 demonstrate the promise of this methodology for accessing organic semiconductors, [13] stimuli-responsive materials, [17] biorthogonal labeling tools, [18] and donor-acceptor polymers (Figure 1c). [17] Despite that more than forty years have passed since Steglichsp ioneering study,k ey mechanistic features of the original DA/r-DAc ascade and variants thereof have remained poorly understood.…”