A multifunctional divergent scaffold to access the formal syntheses of various sesquiterpenoids

Abstract

The development of a divergent scaffold able to access an array of diverse natural sesquiterpenoids is described. The route unifies the scope of previously reported plans of our group to...

Selective preparative ‘oxidase phase’ in sesquiterpenoids: the radical approach

“…16 The group highlighted the efficiency of the method in the synthesis of the common scaffold 36 that served as a multipurpose intermediate for total syntheses and for accessing sesquiterpenoid core structures (Scheme 3). 17 More specifically, acrylic acid 34 reacts with PIDA and iodine to form intermediate 35 , which can be photochemically cleaved to provide a long-lived carboxyl-radical able to initiate a 1,5-hydrogen atom transfer to the respective iodide (structure not shown). The latter is readily cyclized under the reaction conditions to allow the synthesis of 36 in 45% yield (78% brsm).…”

“…Subsequent alkylation of both resulted in 41a and b and 43 that served as points of divergence to access germacranolides and guaianolides through oxy–Cope reactions 16 and furo sesquiterpenoids by cycloisomerizations. 17 Worth mentioning is the ability of sulfur-ylides to serve as convenient precursors for C-6 oxidation.…”

“…65 Based on earlier findings of the group, non-natural elemane-type sesquiterpenoids can serve as ideal precursors to access germacranolides and guaianolides through an oxy–Cope-(ene) reaction (cascades). 17 Applying an oxy–Cope/ene sequence to a diasteroisomeric mixture of 241 ( anti : syn = 4 : 1), readily accessible from ( R )-carvone ( 33 ) in 7 steps, led to germacrane 242 and guaiane 243 as a 50 : 50 mixture in 70% yield (Scheme 24). Interestingly, the isopropenyloxy-TBS substituent at the 4-position was found essential to lock the desired chair conformations for the oxy–Cope event to deliver only the correct stereochemistry for Apiaceae guaiane sesquiterpenoids (Scheme 24).…”

Expanding Natural Diversity: Tailored Enrichment of the 8,12-Sesquiterpenoid Lactone Chemical Space through Divergent Synthesis

“…With multigram quantities of ( R )-carvonic acid ( 4 ) in our hands, we next turned our attention to the key direct syn -8,12-lactonization step. To scale this reaction up, the NBS radical allylic bromination/cyclization sequence to afford 8 previously developed by our group resulted in inconsistent results and low yields (28%). Attempts to optimize the yield by direct allylic oxidation and carboxyl as a directing group to induce CH lactonization by known protocols − failed to provide the desired 8,12-lactone.…”

Short Scalable Route to Apiaceae Sesquiterpene Scaffolds: Total Synthesis of 4-epi-Epiguaidiol A

“…Earlier studies from our group revealed that the utilization of the oxy-Cope reaction and a subsequent ene-reaction in unnatural elemane 1 can provide a convenient route to the synthesis of furan germacrane and Asteraceae guaiane-type sesquiterpenoids (Scheme ). Analysis of the stereochemical outcome of the delivered Asteraceae guaianes in these processes led to knowledge that the tertiary carbon at 1-position was the crucial element for achieving high stereocontrol. Consequently, elemane 5 bearing an epimeric tertiary center at the 1-position was projected as an ideal candidate for accessing Apiaceae sesquiterpenoids (Scheme ).…”