Cyclizations of hydroxy dithioketals. New synthetic technology for the construction of oxocenes and related medium-ring systems

Recent Applications of the Suzuki-Miyaura Cross-coupling to Complex Polycyclic Ether Synthesis

“…Introduction of the C19 axial methyl group was successfully achieved by m CPBA oxidation of the sul de moiety at 78 C followed by in situ treatment of the putative sulfoxide with excess amounts of Me 3 Al and warming the mixture to room temperature. This one pot oxidative activation of the sul de and stereoselective methylation 16 furnished the desired pentacyclic polyether 39 in 94% yield as a single isomer. A three step sequence of careful protecting group manipulations then delivered alcohol 11.…”

“…9 This is the rst use of a lactone derived enol triate as substrate in the Suzuki Miyaura cross coupling. Stereoselective hydroboration of enol ether 4 thus obtained followed by oxidation of the resultant alcohol led to ketone 5, from which the polycyclic ether skeleton 7 could be constructed by treatment with EtSH in the presence of Zn(OTf) 2 and subsequent radical reduction 16 of the derived mixed thioacetal 6. Alternatively, oxidation of the sul de with m CPBA to the corresponding sulfoxide or sulfone, followed by treatment with Me 3 Al, allowed for the introduction of an angular methyl group to give 8.…”

“…Alternatively, oxidation of the sul de with m CPBA to the corresponding sulfoxide or sulfone, followed by treatment with Me 3 Al, allowed for the introduction of an angular methyl group to give 8. 16,17 We next extended the Suzuki Miyaura coupling strategy to the synthesis of polycyclic ethers containing medium sized cyclic ethers. However, Suzuki Miyaura coupling of cyclic enol tri ates was limited to the reactions of six membered rings, and seven membered enol tri ates could not be employed due to their instability under the aqueous basic conditions used in the coupling.…”

Recent progress in the synthesis of oxepanes and medium ring ethers

“…Very recently, the Nicolaou lab applied a milder version of this reductive cyclization, in the form of a hydroxyl-thioketal reductive cyclization 76 during their preparation of the QRSTU ring system of maitotoxin (Scheme 34). 77 Following conversion of the ketone in 167 to the dithioketal, treatment with …”

Convergent Syntheses of the WXYZ Ring of Maitotoxin and the HIJK Ring of Brevisulcenal-F

“…The 6/7/6/6-tetracyclic ether system A corresponding to the WXYZ ring of MTX is to be derived from C through the construction of the tetrahydropyran ring via methylation of a mixed-thioacetal reported by Nicolaou 10 in an analogous manner as previously reported. 7 The seven-membered ring ketone C could be derived from six-membered D by the ring-expansion reaction reported by Mori, 11 and the cyclic ketone D can be traced back to an acyclic saturated ketone E via cyclodehydration giving a dihydropyran followed by hydroboration as reported by Crimmins 12 and Nakata.…”