Total Syntheses of Rhodomollins A and B

Total Synthesis of Principinol B

“…Surprisingly, Mukaiyama hydration [22] of 18 provided pentacycle 19 instead of tertiary alcohol. It seemed that the S N 2 substitution of the Williamson ether synthesis on this substrate was a spontaneous reaction, which was also different from our previous experience [7c] …”

“…Dihydroxylation of 17 at C5=C6 double bond with OsO 4 followed by selective mesylation of the secondary alcohol afforded 18 in 65 % yield over two steps. Different from our previous total syntheses of rhodomollins A and B, [7c] the transformation of the 1,2‐diols to cyclic sulfonate failed on the dihydroxylation product of 17 . To install the oxabicyclo[3.2.1] core structure, we set to introduce a tertiary hydroxyl group at the C10 position.…”

“…Principinol B ( 1 , Scheme 1), isolated by Hou and co‐workers in 2014, [11] is a structural representative in which the C5 configuration is opposite to that of typical grayanoids. Although a similar stereogenic center was pre‐introduced in the A‐ring fragment in our recent convergent and modular total syntheses of rhodomollins A and B, the C1 stereogenic center could not be established directly and concisely [7c] . Herein, we report the first and asymmetric total synthesis of principinol B by direct introduction of the C1 and C5 stereogenic centers and construction of the central seven‐membered ring by carbonyl–olefin metathesis.…”

“…To date, 18 total syntheses of grayanoids have been accomplished by seven research groups [2–8] . Several methods have been developed to construct the tricky seven‐membered carbon ring, [10] such as photo‐santonin rearrangement by the Matsumoto group [2] and Ding group, [5c] SmI 2 ‐promoted intramolecular pinacol coupling by the Shirahama group, [3] SmI 2 ‐promoted intramolecular reductive coupling of aldehyde and enone by the Newhouse group, [4] oxidative dearomatization‐induced intramolecular Diels–Alder reaction [5a] and photo‐Nazarov cyclization [5b] by the Ding group, bridgehead carbocation‐induced Prins cyclization by the Luo group, [6] intramolecular vinylogous aldol reaction [7a] and lithium‐halogen exchange/intramolecular nucleophilic addition to aldehyde [7c] by our group, intramolecular Pauson–Khand reaction by the Jia group, [8] and Dieckmann condensation by the Williams group [9f] . Considering the diversity of stereogenic centers on the seven‐membered carbon ring of grayanoids, new strategies are still in high demand to assemble the medium‐sized ring with specific stereochemistry.…”

“…We first undertook a retrosynthetic analysis of 1 (Scheme 1). Inspired by our experience with rhodomollins A and B, we recognized that the oxabicyclo[3.2.1] core could be assembled from 2 by the Williamson ether synthesis [7c] . The dihydroxyl groups at C5 and C6 position could be introduced by a dihydroxylation reaction, in which stereochemistry could be controlled by the configuration of C1 position.…”