Model studies of the overall 5-endo-trig iodocyclization of homoallylic alcohols

Two Contrasting Asymmetric Approaches to Muscarine Based on 5‐endo‐trig Cyclisations

“…As expected, the key ''iodocyclisation'' step then gave a respectable 63% isolated yield of the desired hydroxytetrahydrofuran 18, whose structure and stereochemistry were established as described previously. [32,33] Also isolated (in an 11% yield) was the epimeric hydroxytetrahydrofuran 19, which is presumably formed by non-selective iodohydrin generation. Traces of iodotetrahydrofuran(s) were also detected which probably arose due to a small amount of (Z)Ǟ(E) isomerisation prior to or during the cyclisation step.…”

“…The stereochemistry of the heterocycle 33 was secured as described previously, and determined by comparisons with related data. [32,33] Initially, the necessary iodine removal was carried out using the tri-n-butyltin hydride-AIBN method [40b] but the inevitably tedious purification led us to seek alternatives, despite obtaining workable 60Ϫ70% yields of the desired product 34a. Fortunately, we found that hydrogenolysis [45] of the iodotetrahydrofuran 33 in the presence of triethylamine, followed by a simple filtration, resulted in an essentially quantitative yield of the de-iodinated product 34a.…”

“…In our earlier model studies, [32] we had established that (E)-homoallylic alcohols (5; R 1 , R 2 ϭ alkyl, aryl) undergo very smooth 5-endo-trig iodocyclisations when treated with three equivalents each of iodine and sodium hydrogencarbonate in acetonitrile under strictly anhydrous conditions to give excellent yields of the iodotetrahydrofurans 7. The transition state conformation 6 appears to account for this stereochemical outcome.…”

Olefin Metathesis−Iodoetherification−Dehydroiodination Strategy for Spiroketal Subunits of Polyether Antibiotics

“…Based on the expected preference for the 6-exo-trig mode of cyclization vs. the other cyclization pathways, we believe the major iodocyclization product to be THP 4 . xix Exposure of the iodocyclization product to silver triflate in the presence of 2,4,6-collidine gave a 2:1 inseparable mixture of spiroketals 3 in 65% yield. The gross structure of 3 was determined by H/H and C/H 2D NMR, but complete stereochemical analysis was not possible at this stage because of the complexity of the spectral data.…”

Synthesis of the Reported Structures for Kealiinines B and C

“…While at first one might expect the formal products of a 5- exo cyclization (pathway b) to outcompete a 6- endo cyclization, there are several examples where the related electrophile-induced cyclizations are successful. 18 Further, donation from the p -methoxy substituent might make this a formal 6- exo cyclization. 19 In our experience the ene-guanidines are not very nucleophilic, suggesting that donation of the neighboring nitrogen lone pair is hampered by steric compression.…”