Enantioselective Synthesis of Arene cis‐Dihydrodiols from 2‐Pyrones

Abstract

An enantioselective chemical synthesis of arene cis‐dihydrodiols has been realized from 2‐pyrones through sequential ytterbium‐catalyzed asymmetric inverse‐electron‐demand Diels–Alder (IEDDA) reaction of 2‐pyrones and retro‐Diels–Alder extrusion of CO2. By using this strategy, a series of substituted arene cis‐dihydrodiols can be obtained efficiently with high enantioselectivity (>99 % ee in many cases). Based on this strategy, efficient and concise asymmetric total syntheses of (+)‐MK7607 and 1‐epi‐(+)‐MK7607 were accomplished.

Enantioselective Synthesis of cis‐Decalin Derivatives by the Inverse‐Electron‐Demand Diels–Alder Reaction of 2‐Pyrones

“…Interestingly, bicyclic or polycyclic cyclohexadienes 4 a – 4 i were obtained with 40–78 % yields and 87–99 % ee in one step through tandem Diels–Alder reaction and in situ retro‐[4+2] extrusion of CO 2 . This observation was in line with our previous finding, that the substituents on the C6 position of 2‐pyrones could facilitate the extrusion of CO 2 from [2,2,2]‐bicyclic lactones …”

“…We firstly selected 2‐pyrone 1 a and silyl cyclohexadienol ether 2 a as diene components to evaluate the reaction. To our delight, in the presence of Yb(OTf) 3 /BINOL L1 (20 mol %), the reaction proceeded through the desired inverse‐electron‐demand fashion smoothly, affording bicyclic lactone 3 a with 80 % yield and 34 % ee (Table , entry 1). Further systematic investigation of 3,3′‐disubstituted BINOL ligands L2 – L8 (entries 2–8) revealed the utilization of L8 bearing pentafluorophenyl moieties led to 3 a in 82 % yield and 91 % ee (entry 8).…”

The Application of Dioxygenase‐Based Chemoenzymatic Processes to the Total Synthesis of Natural Products

“…The prospects for further exploitation of such metabolites is considerable, not least because of the opportunities for generating new forms of these by, for example, applying the currently known suite of dioxygenases to new aromatic substrates. Furthermore, mutant forms of such enzymes are also likely to emerge that enable alternate selectivities to be achieved in the biotransformation of a wide range of arenes (interestingly, strictly chemical means for the enantioselective synthesis of cis ‐1,2‐dihydrocatechols have been reported very recently). As such the possibilities for generating new cis ‐1,2‐dihydrocatechols as starting materials for chemical synthesis are considerable.…”

Inverse‐Electron‐Demand Diels–Alder Reactions of 2‐Pyrones: Bridged Lactones and Beyond

“…[67] More recently,a ni mproved and efficient version of this strategy was achieved by Cai and co-workers,i nw hich as eries of bridged bicyclic lactones 179 and arene cis-dihydrodiols 182 were obtained in good yields with excellent enantioselectivities (Scheme 47). [68] After extensive screening of chiral ligands in combination with Yb(OTf) 3 ,t hey found that the introductiono fp entafluorophenyl groups on 3,3'-positions of (R)-BINOL resulted in dramatical increase of yield and ee value.I nterestingly,w ith catalysis by the combinationo fY b(OTf) 3 and chiral ligand (R)-178,t he cycloadditionso f4 ,5-disubstituted-3carboalkoxyl-2-pyrones 177 with 2,2-dimethyl-1,3-dioxole 132 a proceeded with almostc omplete enantioselectivities (Scheme 47 a), whereas the cycloadditions of more encumbered 6-substituted-3-carboalkoxyl-2-pyrones 180 with 2,2-dimethyl-1,3-dioxole 132 a did not afford bridged bicyclic lactones 181 but directly generated arene cis-dihydrodiols 182 with excellent enantioselectivities (Scheme 47 b). Both the congested scaffold of intermediates TS-182 and the stabilization of C6-carbocation by substituents favored CO 2 extrusion under very mild conditions.…”