Synthesis of complex benzenoids via the intermediate generation of o-benzynes through the hexadehydro-Diels-Alder reaction

Abstract

The hexadehydro-Diels–Alder (HDDA) cascade enables the synthesis of complex benzenoid products with various substitution patterns via aryne intermediates. The first stage of this cascade involves generation of a highly reactive ortho-benzyne intermediate by a net [4+2] cycloisomerization of a triyne substrate. The benzyne can be rapidly ‘trapped’ either intra- or intermolecularly with a myriad of nucleophilic or π-bond-donating reactants. As a representative example of a general procedure to synthesize highly substituted benzenoids, this protocol describes the synthesis of a typical triyne substrate and its use as the reactant in an HDDA cascade to form a phthalide. The synthetic procedure detailed herein (four chemical reactions) takes 16–20 h of active effort over a several day period for preparation of the triyne precursor and ~2 h of active effort over a 3-day period for generation and trapping of the benzyne and isolation of the phthalide product.

Blue-Emitting Arylalkynyl Naphthalene Derivatives via a Hexadehydro-Diels–Alder Cascade Reaction

“…(b) The HDDA thermal cycloisomerization 2,3 ( 5 to 6 ) produces benzynes that are more complex and diverse in structure; trapping with myriad dienes like 7 is envisioned to produce novel highly conjugated adducts like 8 .…”

The Hexadehydro-Diels–Alder Cycloisomerization Reaction Proceeds by a Stepwise Mechanism

“…1 In the latter, a 1,3-diene is engaged by a dien ophile; in the former, a 1,3-diyne by an alkynyl diyn ophile. 2 The latter typically results in cyclohexene formation; the HDDA reaction leads to benzyne (or hexadehydrocyclohexene) formation ( 1 to 2 , Figure 1a).…”

“…1,8 The products 9a-g are formed via the HDDA cascade comprising initial, rate-limiting cycloisomerization of 7 to benzynes 8 followed by rapid trapping by the pendant silyl ether. In every instance, product 9 was, by far, the major product formed and, most often, the only product observed.…”

Alkane desaturation by concerted double hydrogen atom transfer to benzyne

“…Arynes 7,8,9 engage in myriad trapping reactions that functionalize adjacent sp-hybridized carbons in the o -aryne ring. We recently reported a general strategy for the formation and subsequent in situ trapping of benzynes via the hexadehydro-Diels–Alder (HDDA) reaction 6,10,11 .…”