Enantioselective Total Synthesis of (−)‐Diversonol

Abstract

For the synthesis of (-)-diversonol (ent-1), an enantioselective domino-Wacker/carbonylation/methoxylation reaction and an enantioselective Wacker oxidation were used to give the chroman in high yield and 96% and 93% ee, respectively. Dihydroxylation at the vinyl moiety using the Sharpless procedure and a Wittig-Horner reaction followed by hydrogenation, benzylic oxidation, and an intramolecular acylation provided the tetrahydroxanthenone, from which ent-1 is accessible in a few steps. Furthermore, the synthesis of the diastereomeric diversonol rac-1,9a-epi-diversonol (rac-41) is also described.

Scope and Limitations of the Domino Vinylogous Aldol/oxa‐Michael Reaction

“…Next, ceric ammonium nitrate was used to oxidatively cleave the p ‐methoxy phenyl group from the hydroxyl group to yield alcohol 34 . The alcohol was oxidized within a two‐step sequence since a direct one‐step oxidation lacks satisfactory yields . Dess‐Martin periodinane oxidation led to the aldehyde 35 in 92 % yield.…”

A Domino Approach to the Enantioselective Total Syntheses of Blennolide C and Gonytolide C

“…The conversion of 9 to chromane 8 was then investigated in the presence of a chiral BOXAX ligand, catalytic amounts of palladium(II)‐trifluoroacetate and the reoxidant p ‐benzoquinone under an atmosphere of carbon monoxide in methanol (Table 1). In line with our syntheses of (−)‐diversonol ( ent ‐ 1 )13 and (−)‐blennolide A,12 we initially utilized the ( S , S )‐Bn‐BOXAX ligand (i.e. 13 , R=Bn) to induce enantioselectivity.…”

“…Direct conversion of a derivative of 9 containing an ethylidene instead of the methylidene group to vinyl chromane 12 by an enantioselective Wacker oxidation had been shown to proceed with low enantioselectivity on related substrates and was therefore avoided 12. 13…”

“…Commercial AD‐mix‐α gave access to the desired anti ‐isomer 14 a , though the yield was only moderate and the anti / syn ratio of 2.4:1 unsatisfactory (Table 2, entry 1). Since the diastereoselectivity of this transformation was equally low in previous syntheses (diversonol: 3.8:1, blennolide A: 2.4:1),12, 13 we decided to survey other commercial dihydroquinine (DHQ) ligands for their ability to carry out the dihydroxylation. Phthalazine‐based (DHQ) 2 ‐PHAL, the chiral ligand present in the commercial mix, gave the expected low selectivity (1:8:1) albeit a higher yield when compared with the premixed AD‐mix‐α (entry 2).…”

“…Our group has recently reported the syntheses of enantiopure (À)-blennolide A, [12] (À)-diversonol (ent-1), [13] 4-dehydroxydiversonol [14] and the proposed structures of paecilin A and B [15] by using an enantioselective domino-Wacker/carbonylation/methoxylation reaction. This versatile domino process [16] has also been applied to the synthesis of chromanes, dioxins and oxazins.…”