Formal [4 + 1] Cycloadditions of β,β-Diaryl-Substituted ortho-(Alkynyl)styrenes through Gold(I)-Catalyzed Cycloisomerization Reactions

Abstract

Gold(I)-catalyzed cycloisomerization of ,-diaryl-o-(alkynyl)styrenes at 80 ºC selectively yields dihydroindeno[2,1-a]indenes in a transformation that encompasses a formal [4+1] cycloaddition and takes place through a cascade 5-endocyclizationdiene activationiso-Nazarov cyclization. In addition, by performing the reaction at 0 ºC, the same substrates exclusively give rise to benzofulvene derivatives, which have also been shown to be intermediates in the formation of the tetracyclics.Gold(I)-catalysis is nowadays well established as a powerful tool for the straightforward construction of complex molecules from readily available starting materials.1 Intense research on this topic during the last decade has demonstrated the unique ability of gold(I) complexes for selectively activating triple bonds towards the attack of a wide range of different nucleophiles.2 In particular, the cycloisomerization of enynes has attracted great interest, and its usefulness has been demonstrated in the construction of intricate carbocyclic skeletons not easily accessible by other methodologies, through the development of diverse cascade processes. 3In this context, we became interested in gold(I)-catalyzed cycloisomerizations of conjugated dienynes, 4 with particular attention to o-(alkynyl)styrenes. 5 Thus, we described an enantioselective synthesis of indenes by gold(I)-catalyzed cycloisomerization of o-(alkynyl)styrenes (Scheme 1, eq. 1). 5aMoreover, we found that when an o-(alkynyl)styrene having a secondary alkyl group at the -position of the styrene moiety is used as starting material, a formal [3+3] cycloaddition occurs, involving the aromatic group initially bonded to the triple bond and finally giving rise to dihydrobenzo[a]fluorenes (Scheme 1, eq. 2).5b In both cases, the reaction is proposed to proceed through a common carbocationic intermediate, which can be also described as a cyclopropyl gold carbene-like intermediate, 6 generated by a 5-endo nucleophilic attack of the olefin to the gold-activated alkyne. This gold intermediate evolves through a proton elimination in the first case and through a more complex cascade process in the second one. Taking these results into account, we wondered about the outcome of the reaction under gold(I)-catalysis of ,-diarylo-(alkynyl)styrenes, for which none of the previously described pathways is available (Scheme 1, eq. 3).Herein we report the gold(I)-catalyzed cycloisomerization of ,-diaryl-o-(alkynyl)styrenes through a cascade process leading to dihydroindeno[2,1-a]indenes by a formal [4+1] cycloaddition process. Scheme 1. Previous Work and Proposed StudyTo start our investigations, we selected ,-diphenyl-o-(ptolylethynyl)styrene 1a as model substrate and performed its reaction with AuPPh 3 NTf 2 as catalyst in DCM as the solvent at room temperature (Scheme 2). Under these conditions and not surprisingly, benzofulvene 2a was obtained as a major product, presumably coming from the elimination of the only proton available in intermediate Ia. More interestingly, a mi-

Recent Advances in the Synthesis of Indenes

“…The usefulness of the 3‐iodoindenes has also been demonstrated by the synthesis of several polysubstituted indene derivatives through conventional palladium‐catalyzed cross‐coupling reactions and iodine–lithium exchange processes. This method complements the 5‐ endo gold‐catalyzed cycloisomerization of o ‐(alkynyl)styrenes developed by the same authors …”

“…The gold(I)‐catalyzed cycloisomerization of β,β‐diaryl‐ o ‐(alkynyl)styrenes ( 65 ) leads either to benzofulvenes 66 or dihydroindeno[1,2‐a]indenes 67 , depending on the reaction conditions (Scheme ) …”

Gold-Catalyzed Homogeneous (Cyclo)Isomerization Reactions

“…In 2016, Sanz et al demonstrated that β,β-diaryl- o -(alkynyl)-styrenes 136 are transformed at 80 °C into dihydroindeno[2,1- a ]indenes 137 under gold(I)-catalysis whereas benzofulvenes 138 are obtained at 0 °C . The formation of the tetracycles 137 implies a formal [4+1] cycloaddition trough a tandem 5- endo -cyclization-diene/iso-Nazarov cyclization process (Figure 12D) (Sanjuán et al, 2016). A computational study for related gold(I)-mediated transformations in which the initial styrenes bear alkyl groups at the β positions has been reported by Zhou et al (2018b) The authors concluded that the reaction would evolve trough a [1,2]-H shift on the isopropyl moiety rather than a cyclopropane expansion, as suggested in the experimental work (Sanjuán et al, 2015).…”

A Rapid and Highly Efficient Method for the Synthesis of Benzofulvenes via CsOH‐Catalyzed Condensation of Indene and Aldehydes

“…However, this condensation gave poor yields both for single and double condensation products. Other processes for the preparation of benzofulvenes involves the intramolecular cyclization of o ‐alkynylstyrenes catalyzed by Au, or in the presence of 3.0 equiv. of NIS ( N ‐iodosuccinimide) .…”