Stereoselective Synthesis of Medium-Sized Cyclic Ethers: Application of C-Glycosylation Chemistry to Seven- to Nine-Membered Lactone-Derived Thioacetals and Their Sulfone Counterparts

Abstract

Stereoselective synthesis of α,α'-substituted medium-sized cyclic ethers has been achieved by means of nucleophilic substitution of the corresponding lactone-derived thioacetals and their sulfone counterparts. Nucleophilic substitution of medium-sized lactone-derived thioacetals could be achieved efficiently either by (i) activation with NIS/TMSOTf in the presence of allyltrimethylsilane or TMSCN or by (ii) oxidation to the corresponding sulfones followed by treatment with an appropriate organometallic species such as divinylzinc or dimethyl(2-phenylethynyl)aluminum. Interestingly, the stereochemical consequence was found to be largely dependent on the local structure of substrates. In some cases, the gauche steric interaction developed in the transition state was considered to be responsible for the observed diastereoselectivity. The present method enables an efficient synthesis of a variety of α,α'-substituted seven- to nine-membered cyclic ethers from readily accessible lactone precursors.

Stereoelectronic Model To Explain Highly Stereoselective Reactions of Seven‐Membered‐Ring Oxocarbenium‐Ion Intermediates

“…[4,5] No systematic study of nucleophilic addition reactions to simple seven-membered-ring oxocarbenium ions has appeared, and no general explanation has been forwarded to explain the reactions of these intermediates. [6] We report herein that nucleophilic substitution reactions of oxepane acetals are highly stereoselective in most cases. We propose am odel to explain these selectivities by considering that nucleophilic attack should occur from the face that minimizes transannular interactions in the first-formed product.…”

“…[4–5] No systematic study of the nucleophilic additions to simple seven-membered ring oxocarbenium ions has appeared, and no general explanation has been forwarded to understand the reactions of these intermediates. [6] …”

Enantio‐ and Diastereoselective Synthesis of Latanoprost using an Organocatalyst

“…Recently,w ef ound that ap rolinate salt was an effective catalystf or the a-aminoxylation of aldehydes. Reduction of the a,b-unsaturated ester with NaBH 4 and NiCl 2 [14] provided 14 in 83 %y ield, and it was reduced with diisobutylaluminum hydride (DIBAL-H) to the aldehyde in 73 %y ield. [12] Protection of the alcohol group with NapBr (Nap = 2-naphthylmethyl), [13] NaH, and tetrabutylammonium iodide (TBAI) afforded the 2-naphthylmethyl ether in 90 %y ield.…”

“…[12] Protection of the alcohol group with NapBr (Nap = 2-naphthylmethyl), [13] NaH, and tetrabutylammonium iodide (TBAI) afforded the 2-naphthylmethyl ether in 90 %y ield. Reduction of the a,b-unsaturated ester with NaBH 4 and NiCl 2 [14] provided 14 in 83 %y ield, and it was reduced with diisobutylaluminum hydride (DIBAL-H) to the aldehyde in 73 %y ield. AH enry reaction with MeNO 2 ,f ollowed by dehydration provided nitroalkene 5 in 85 %y ield.…”

Total Synthesis and Complete Structural Assignment of Gambieric Acid A, a Large Polycyclic Ether Marine Natural Product

“…In addition to this important result, the distinctive features of our total synthesis include the use of our developed variant of the Suzuki–Miyaura coupling for the convergent union of the complex polycyclic ether fragments (A/BCD‐ and F′GHIJ‐ring fragments), a strategy for the introduction of the C25 stereogenic center that relies on the inherent conformational properties of the unnatural F′‐ring, stereoselective allylation of the E‐ring thioacetal using glycosylation chemistry, and the novel example of a CeCl 3 ‐promoted Julia–Kocienski olefination to form the trisubstituted ( E )‐olefin within the J‐ring side chain. Significantly, C ‐glycosylation of medium‐sized thioacetals proved to be a versatile method for stereoselective synthesis of medium‐sized cyclic ethers and helped further our understanding of the stereoselectivity of nucleophilic addition to medium‐sized oxocarbenium ions [64]. Furthermore, our total synthesis enabled the preparation of non‐natural analogues that provided information on the structure–activity relationships of this intriguing natural product.…”