Xiao Xiao discloses new and powerful domino hexadehydro-Diels-Alder (HDDA) reactions
Xiao Xiao, a senior graduate student working in Professor Thomas Hoye's research group, recently reported that properly designed polyyne substrates, merely upon being heated, undergo an efficient, domino sequence of net [4+2] cycloaddition reactions initiated by (rate-limiting) benzyne formation. These proceed through naphthyne, anthracyne, and/or tetracyne intermediates. Rapid, bottom-up synthesis of highly fused, polycyclic aromatic compounds results.
In the 2018 August issue of Nature Chemistry,1 Xiao and Hoye report numerous examples of reactions between polyyne substrates with various aryne trapping reagents to afford products of substantially increased structural complexity in a single step. This study demonstrates yet another facet of the power of the hexadehydro-Diels–Alder (HDDA) reaction in the fields of both organic synthesis and materials chemistry,2 a current significant focus of the Hoye group’s research.
One particularly impressive example of this domino-HDDA reaction is the generation of the tetracyne intermediate 3 from nonayne 1—a purely thermal process that results in formation of multiple C–C bonds and new rings (Fig. 1). In the presence of the trapping agent 2 this gives a precursor of hexacene 4.
1The domino hexadehydro-Diels–Alder reaction transforms polyynes to benzynes to naphthynes to anthracynes to tetracynes (and beyond?) Xiao, X.; Hoye, T.R. Nature Chemistry 2018, 10, 838–844.
2 (a)Reactions of hexadehydro-Diels–Alder benzynes with structurally complex multifunctional natural products. Ross, S.P.; Hoye, T.R. Nature Chemistry 2017, 9, 523–530. (b)The pentadehydro-Diels–Alder reaction. Wang, T.; Naredla, R.R.; Thompson, S.K.; Hoye, T.R. Nature 2016, 532, 484–488. (c)The aromatic ene reaction. Niu, D.; Hoye, T.R. Nature Chemistry 2014, 6, 34–40. (d)Alkane desaturation by concerted double hydrogen atom transfer to benzyne. Niu, D.; Willoughby, P.H.; Baire, B.; Woods, B.P.; Hoye, T.R. Nature 2013, 501, 531–534. (e)Synthesis of complex benzenoids via the intermediate generation of o-benzynes through the hexadehydro-Diels-Alder reaction. Baire, B.; Niu, D.; Willoughby, P.H.; Woods, B.P.; Hoye, T.R. Nature Protocols 2013, 8, 501–508. (f)The hexadehydro-Diels–Alder reaction. Hoye, T.R.; Baire, B.; Niu, D.; Willoughby, P.H.; Woods, B.P. Nature 2012, 490, 208–212 (link).