In asingle photochemical operation (l ! 350 nm) an easily accessible indanone derivative was converted into as tructurally complex precursor of the protoilludane sesquiterpenes.T he product (60 %y ield) contains all 15 carbon atoms of the skeleton in the required connectivity and was transformed into the natural product atlanticone C( 9s teps, 6% overall yield). In addition, it was shown that other protoilludanes,s uch as D 6 -protoilludene and paesslerin A, can be prepared in aconcise fashion via the photochemical key intermediate.T he photochemical reaction cascade comprises an ortho photocycloaddition, athermal disrotatory ring opening and ar egioselective disrotatory [4p]p hotocyclization.The protiolludane skeleton A (Figure 1) represents an intriguing natural product scaffold and is the hallmark of many biologically active sesquiterpenes.Acentral cyclohexane ring is flanked by ac yclobutane ring with aq uaternary carbon center C-3 and by a gem-dimethyl-substituted cyclopentane ring at positions C-2 and C-9. Thep rotoilludane biosynthesis [1] from farnesyl pyrophosphate via cationic intermediates is testimony to the masterful ability of nature to create molecular complexity from simple building blocks. Representative sesquiterpenes with this structure element include atlanticone C( 1), [2] D 6 -protoilludene (2), [3] and paesslerin A( 3). [4] Many synthetic approaches have been described to tackle the challenging core structure of the protoilludanes. [5] One set of syntheses aimed at ac onstruction of the tricyclic skeleton from acyclic or monocyclic precursors in amanner mimicking their biological genesis from humulene. [6] In several other approaches,t he rings were built consecutively, [7] with the construction of the cyclobutane ring requiring particular attention. Notable photochemical strategies [8] to secure formation of the four-membered ring include the common [2+ +2] photocycloaddition [9] but also some less frequently used methods such as the photochemical 1,3-acyl shift reaction of b,g-unsaturated enones. [10] Our interest in protoilludanes was triggered by recent work [11] on ar eaction cascade [12] that is initiated by an ortho photocycloaddition and that generates the bicyclo[4.2.0]octane skeleton, acore element of structure A,inasingle operation. Herein, we disclose aconcise access to protoilludane sesquiterpenes that culminated in the first total synthesis of atlanticone C( 1)a nd in the stereoselective synthesis of two other advanced intermediates that had been previously converted into D 6 -protoilludene (2)a nd paesslerin A( 3).Arenes B (Scheme 1), which have ac arbonyl group in ortho position to an alkenyloxy group,are known to undergo an initial [2+ +2] photocycloadditon at the arene (ortho photocycloaddition [13,14] ). Products C are unstable and form cyclooctatrienes D through ad isrotatory ring opening.I ns ome cases,t hese products have been isolated [15] but the most frequent reaction pathway is ac onsecutive disrotatory [4p] Figure 1. The protoilludane skeleton A and representa...

The arene ring of the title compounds is cleaved by a reaction cascade which is initiated by an intramolecular ortho photocycloaddition reaction. Tricyclic products were obtained in a highly regio- and diastereoselective fashion via a cyclooctatriene intermediate. The facial diastereoselectivity exerted by a stereogenic center in the tether is moderate to good (dr = 65/35 to 82/18). Yields were acceptable (44-87%) except for a single substrate which had a geminal dimethyl substitution in the tether and which gave the respective product in only 14% yield. The reaction is stereoconvergent with regard to the olefin configuration ( E or Z) in agreement with a triplet mechanism of the ortho photocycloaddition step.

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.

In asingle photochemical operation (l ! 350 nm) an easily accessible indanone derivative was converted into as tructurally complex precursor of the protoilludane sesquiterpenes.T he product (60 %y ield) contains all 15 carbon atoms of the skeleton in the required connectivity and was transformed into the natural product atlanticone C( 9s teps, 6% overall yield). In addition, it was shown that other protoilludanes,s uch as D 6 -protoilludene and paesslerin A, can be prepared in aconcise fashion via the photochemical key intermediate.T he photochemical reaction cascade comprises an ortho photocycloaddition, athermal disrotatory ring opening and ar egioselective disrotatory [4p]p hotocyclization.

The first enantioselective total synthesis of (+)-atlanticone C is described. The complex tricyclic protoilludane core was rapidly assembled by a photochemical reaction cascade starting from an easily accessible indanone precursor (3 steps). Optimization of an enantioselective Corey–Bakshi–Shibata reduction permitted a catalytic chiral reso­lution of the racemic photoproduct (45% over two steps; up to 98% ee). The enantiomerically enriched photoproduct was efficiently transformed into the (+)-enantiomer of atlanticone C (10 steps; 18% yield), and the absolute configuration of naturally occurring (–)-atlanticone C was thereby determined.