Stereodivergent Photoelectrocyclization Reactions of Bis-aryl Cycloalkenones: Intercepting Photoelectrocyclization Intermediates with Acid

Abstract

Described here are tandem photoelectrocyclization and [1,5]-hydride shift reactions of heteroaryl-containing bis-aryl cyclohexenone derivatives that give heteroaryl-substituted dihydrophenanthrenes. This Letter demonstrates that electrocyclization intermediates can be trapped with acid when the [1,5]-hydride shift is relatively slow. From a practical perspective, the observation that the acid-mediated reaction gives a divergent stereochemical outcome when compared with the reaction run under neutral conditions makes these transformations powerful.

Photoelectrocyclization Reactions of Conjugated Cycloalkenones: Scope and Reactivity

“…From the triplet-excited states of 59 and 60, there are two mechanistic possibilities for the generation of 61 and 62: (1) a disrotatory electrocyclization followed by a suprafacial [1,5]hydride shift or (2) a conrotatory cyclization followed by a deprotonation−protonation sequence. 19 To investigate which of these were more likely, we examined deuterium-labeled cyclization precursor 67 (Scheme 8). The requisite deuterons were incorporated into 2-phenyl indole 63 employing the conditions of Dong and co-workers and a Ru-catalyzed deuterium incorporation reaction to provide 64 in 94% yield.…”

“…9,10 As we reported previously, the stereoselectivity of the photoelectrocyclization of several six-membered N-heterocyclic arenes can be influenced by the reaction conditions. 19 Specifically, pyrazines 69 and 71 and quinoxaline 73 gave nearly exclusive cis-products 70, 72, and 74, respectively, when the photoreactions were carried out in the presence of an acid (trifluoroacetic acid, TFA) and exclusively trans-products when the acid was absent (Table 3, entries 1−6). While pyridine containing precursors were not as selective, they were at least as intriguing; the use of 77 gave mixtures of cis-and trans-dihydrophenanthrenes 78 when TFA was introduced into the reaction mixture and exclusively trans-78 when TFA was absent (entries 9 and 10).…”

“…We had previously reported that 81 undergoes exclusive electrocyclic ring-opening when subjected to 350 nm light but that it is converted into cis-fused 82 from a photoelectrocyclization−protonation sequence when subjected to light in the presence of TFA (Scheme 11). 19 Each of these latter results demonstrates that the dearomatized electrocyclization intermediate can be intercepted when the [1,5]-hydride shift is relatively slow.…”

Biphenyl Cyclobutenone Photoelectrocyclizations

“…For example, cyclobutenones have been employed in pericyclic reactions as both precursors to dienes and as dienophiles for Diels–Alder reactions, while cyclobutanones have been utilized in a range of ring expansion and fragmentation reactions. − In light of what we saw as a wealth of possibilities, we became intrigued with the use of cyclobutenones in photoelectrocyclization cascades as a means of generating fused cyclobutanones ( 1 – 2 , Scheme ). Although this reaction sequence lacked precedent when we began these efforts, it would result in the synthesis of fused cyclobutanones that might be useful in the synthesis of other scaffolds made it intriguing to us.…”

“…In support of this concern, we calculated that trans -fused bicyclo[2.4.0]­octadienone 3 was about 10 kcal/mol higher in energy than the corresponding cis -fused isomer 4 (Figure ). , In spite of this, we were encouraged by our and others observation that some substrates proceed through triplet excited states and the possibility that a triplet-derived reaction might lead to the more stable cis -fused product. ,, Equally encouraging was the possibility that the electrocyclization intermediate from a singlet excited state could be protonated to give cis -fused products. , The work described here provides details about our efforts to overcome these obstacles in our quest to execute the cyclobutenone photoelectrocyclization strategy.…”