Complex Carbocyclic Skeletons from Aryl Ketones through a Three‐Photon Cascade Reaction

Abstract

Starting from readily available 7‐substituted 1‐indanones, products with a tetracyclo[5.3.1.01,704,11]undec‐2‐ene skeleton were obtained upon irradiation at λ=350 nm (eight examples, 49–67 % yield). The assembly of the structurally complex carbon framework proceeds in a three‐photon process comprising an ortho photocycloaddition, a disrotatory [4π] photocyclization, and a di‐π‐methane rearrangement. The flat aromatic core of the starting material is converted into a functionalized polycyclic hydrocarbon with exit vectors in three dimensions. Ring opening reactions at the central cyclopropane ring were explored, which enable the preparation of tricyclo[5.3.1.04,11]undec‐2‐enes and of tricyclo[6.2.1.01,5]undecanes.

Concise Total Synthesis of (+)-Atlanticone C

“…With 4 in hand, we focused on the key step of our synthetic strategy, the photochemical reaction cascade furnishing the protoilludane core. Previous experiments 11,12,14 had shown that the desired photochemical transformation proceeds efficiently in freshly distilled dry methanol as the solvent (0.1 mΜ) and with irradiation at  = 300 or 350 nm. We were pleased to detect reasonably good conversions of 4 after irradiation at  = 300 and 350 nm for two hours ( Table 1, entries 1 and 2, respectively).…”

“…Our modified approach commenced with the synthesis of photosubstrate 4, which was easily accessible in three steps starting from p-methylanisole (see Supporting Information). 11,14 The idea was to resolve the putative reaction product by a subsequent enantioselective reduction, which required a steric distinction of the substituents at the carbonyl carbon atom. The introduction of the gem-dimethyl substitution at C-11 was therefore postponed to a later stage after the resolution had been performed.…”

“…Because of the overall better enantioselectivity toward alcohol 7a, we decided to pursue our total synthesis with this diastereoisomer. The absolute configuration of alcohol 7a was confirmed by Mosher analysis 22,23 of the two epimeric esters 9a and 9b, obtained by esterification 24 with the ap-Scheme 1 Mechanism of the photochemical reaction cascade furnishing the protoilludane core E [10][11][12][13][14] O Y…”

“…Mechanism of the photochemical reaction cascade furnishing the protoilludane core E[10][11][12][13][14] …”

“…The resulting strained diene intermediate C undergoes a thermal disrotatory ring opening, forming triene D. Upon further irradiation, a [4]-photocyclization occurs that converts D into the desired cyclobutene product E featuring three stereogenic centers. 11,12 We also observed that under certain conditions, the product can undergo a third photochemical step, a di--methane rearrangement leading to the cyclopropane product F. 14 Whereas the above-mentioned approach led to a synthesis of racemic atlanticone C, we have now attempted to synthesize the compound in an enantiopure form. Apart from obtaining proof of the absolute configuration of the product, we also expected to improve some of the consecutive steps, and we wanted to showcase the utility of the photochemical reaction cascade.…”