Development of an Alkyne Analogue of the de Mayo Reaction: Synthesis of Medium‐Sized Carbacycles and Cyclohepta[b]indoles

Abstract

Embedded medium-sized carbacycles and cyclohepta [b]indoles occur frequently as scaffold elements in natural products and bioactive compounds.Described herein is ac onceptionally novel photochemically triggered cascade process to these scaffolds.K ey to the cascading ring-expansion process is an unprecedented intramolecular alkyne analogue of the de Mayor eaction.

Chemoselective light‐induced reactivity of β‐enaminones

“…As we had postulated the formation of enaminone (assisted by catalytic amounts of formic acid) that was generated in situ during the course of the photoreaction (Scheme 1), we independently synthesized the enaminone by thermal method. 27,28 Analysis of the enaminones derived from the thermal reaction of cyclic β-diketones 1/2 with o-vinlyanilines 3a-c showed that the endocyclic enaminone-8 was favored over exocyclic enaminone-9 for 2-acetylcyclohexanone 1, while the exocyclic enaminone-10 was favored over endocyclic enaminone-11 for 2-acetylcyclopentanone 2. 27 This was in line with the Dieckmann-Kon rule 23,24 where the endocyclic systems are favored over the exocyclic systems for reaction involving six-membered skeletons while the reversal is true for five-membered systems.…”

“…It was clear that there was a reversal in chemoselectivity when the diketone was changed from 2‐acetylcyclohexanone 1 to 2‐acetylcyclopentanone 2 , that is, the photoproduct featuring the vinylic methyl substituent was preferred in hexacyclic system (product 4 over 5 ), while the photoproduct featuring the bridge head methyl substituent was preferred in pentacyclic system (product 6 over 7 ). As we had postulated the formation of enaminone (assisted by catalytic amounts of formic acid) that was generated in situ during the course of the photoreaction (Scheme 1), we independently synthesized the enaminone by thermal method 27,28 . Analysis of the enaminones derived from the thermal reaction of cyclic β‐diketones 1 / 2 with o ‐vinlyanilines 3a‐c showed that the endocyclic enaminone‐ 8 was favored over exocyclic enaminone‐ 9 for 2‐acetylcyclohexanone 1 , while the exocyclic enaminone‐ 10 was favored over endocyclic enaminone‐ 11 for 2‐acetylcyclopentanone 2 27 .…”

“…The formation of endocyclic and exocyclic enaminones was unambiguously determined by single crystal XRD analysis as we were successful in crystalizing endocyclic enaminone 8c (Scheme 4). 27 We then subjected the enaminones (synthesized by thermal methods) 27,28 to our standard irradiation conditions. Irradiation of methanolic solution of as synthesized endocyclic enaminone 8a (with traces of isomer exocyclic enaminone 9a ) at ~350 nm under nitrogen atmosphere yielded the photoproduct 4a (featuring a vinylic methyl substituent) as the major isomer and 5a as the minor isomer (featuring a bridge head methyl substituent) with an overall yield of 57% (Scheme 4‐top).…”

Photochemical Approach to the Cyclohepta[b]indole Scaffold by Annulative Two‐Carbon Ring‐Expansion

“…To complement the existing methodology, we aimed for a fuse – compress – expand sequence to 6,7‐dihydro‐cyclohepta[ b ]indol‐8(5 H )‐ones 4 that exploits an unprecedented photochemically triggered two‐carbon ring‐expansion (Figure ) . Fusing is accomplished by Sonogashira cross‐coupling between o ‐iodo anilines ( 5 ) and terminal alkynes ( 6 ), followed by condensation with five‐membered cyclic 1,3‐dicarbonyl compounds ( 7 ) and finalized by N ‐acylation to deliver photochemistry‐competent vinylogous amides 8 .…”

Analysis of Organophotocatalyst-Substrate Interactions for Understanding Triplet-Triplet Back Energy Transfer

“…However, a thorough reaction-screening showed an exceptional example; the catalytic performance of the organoPCs was extremely different in DeMayo-type [2 + 2] cycloaddition [23][24][25][26][27][28][29] via EnT despite their similar excited energies. A showed an excellent catalytic e ciency for the reaction between methyl-2-(quinolin-2-yl)acetate (MQ) and styrene, whereas the tetracyclic variant B did not promote the same process well (Fig.…”