A Practical Route to Enantiopure, Highly Functionalized Seven-Membered Carbocycles and Tetrahydrofurans: Concise Synthesis of (+)-Nemorensic Acid

Recent developments in chiral non-racemic sulfinyl group chemistry in asymmetric synthesis

“…This strategy was successfully applied to the total synthesis of (+)-nemorensic acid 153 (Scheme 64). 123 Interestingly, switching from a sulfoxide to a sulfoximine auxiliary, allowed a complete inversion of the stereoselectivity. 124 Furthermore, this methodology was extended to the intramolecular acetoxypyranone-vinylsulfoxide cycloaddition.…”

Highly diastereoselective 1,3-dipolar cycloaddition reactions of trans-2-methylene-1,3-dithiolane 1,3-dioxide with 3-oxidopyridinium and 3-oxidopyrylium betaines: a route to the tropane skeleton

“…The X-ray crystal structure of 11 provides an answer: the H-7 endo proton is in close proximity (syn-axial) to a sulfoxide oxygen, and so experiences a pronounced anisotropic effect characteristic of the sulfoxide group on a 1,3-parallel hydrogen. 11 In contrast, H-7 exo is in the proximity of a sulfoxide lone pair and will not be affected. The pronounced downfield shift of H-6 endo in the minor isomer 12 must therefore be due to a similar anisotropic effect from the sulfoxide, and so its stereochemistry must be as shown.…”

“…Cycloadduct 12 eluted first and was obtained as a yellow oily solid (410 mg, 21%). R f (10% EtOH-EtOAc) 0.4; δ H (400 MHz; CDCl 3 ) 2.38 (1H, dd, J 14 and 6, 6-H exo ), 2.69 (1H, d, J 14, 6-H endo ), 3.49 (1H, td, J 14 and 4, CHS(O)), 3.54-3.63 (2H, m, 2 × CHS(O)), 3.76 (1H, td, J 14 and 2, CHS(O)), 3.86 (1H, d, J 13, 9-H), 3.87-3.91 (1H, m, 5-H), 4.12 (1H, t, J 1, 1-H), 6.26 (1H, dd, J 10 and 1, 3-H), 7.10 (1H, dd, J 10 and 5, 4-H), 7.23-7.34 (5H, m, Ar-H); m/z (EI) 335 (M ϩ , 5%), 275 (10), 227 (11), 211 (37), 185 (18), 91 (100). Although the title compounds could not be separated using flash chromatography reduction of the enone double bond using the procedure of Mahoney et al 20 gave two ketones 25 and 26 that could be readily separated.…”

Pyrrolizidine alkaloids

“…At about the same time, Mascareñas employed a formally analogous strategy to access (+)-nemorensic acid. 91 Key to this approach was the diastereoselective intramolecular oxidopyrylium cycloaddition of chiral sulfoxide 158 (Scheme 6). The sulfoxide acted as an effective chiral auxiliary in this reaction to provide a 93 : 7 ratio of (5 + 2)-cycloadducts.…”