Diastereoselective Epoxidation of Cyclohexene Derivatives by Dioxiranes Generated in Situ. Importance of Steric and Field Effects

Abstract

In this paper, diastereoselective epoxidation of substituted cyclohexenes (substrates 1-7) by dioxiranes generated in situ from ketones and Oxone was systematically investigated. The results revealed that the diastereoselectivity was determined by the steric and field effects of both dioxiranes and substrates, and high diastereoselectivity can be achieved by tuning the ketone structure. Among the ketones tested, 12 and 19 gave the best diastereoselectivities.

Synthesis of the 1,6,8-trioxadispiro[4.1.5.2]tetradec-11-ene ring system present in the spirolide family of shellfish toxins and its conversion into a 1,6,8-trioxadispiro[4.1.5.2]-tetradec-9-en-12-ol via base-induced rearrangement of an epoxide

“…This can be rationalised by significant steric interactions involving the bulky tert-butyldiphenylsilyl ether which disfavour the approach of dimethyldioxirane from the b face. Dipole-dipole repulsions, which would also disfavour b approach, 23 reinforce the steric influence upon facial selectivity for the syn configurations cis syn 12a and trans syn 12b, due to the b disposition of the central ring oxygen with respect to the C-11=12 double bond. Epoxides 33a, 33b, 33c were therefore all assigned as a and this assignment was later verified by the successful execution of the base-induced rearrangement reaction.…”

“…Removal of the solvent under a reduced pressure, followed by flash column chromatography using hexane-diethyl ether (9 : 1) as eluant afforded a 1 : 1 mixture of the title compounds 32a, 32b (54 mg, 90%) as a colourless oil [Found (CI, NH 3 ): MH + , 609.3791. C 36 H 57 O 4 Si 2 requires M r , 609.3795]; m max /cm −1 (CDCl 3 ): 3053,2986,2959,2876,2305,1422,1265,1111,1079,1018,895,736; d H (300 MHz, CDCl 3 ): 0.57 (6H, q, J 8.0, SiCH 2 CH 3 ), 0.82-0.91 (12H, m, Me and SiCH 2 CH 3 ), 1.05 (9H, s, Si t BuPh 2 ), 1.48-2.29 (11H, m, H-1 , H-2 , H-3, H-4, H-4 and H-8), 3.64-3.77 (3H, m, H-5 and H-7 ax ), 3.80-3.84 (1H, m, CHOSi, H-3 ), 3.92-4.01 (1H, m, CH ax H eq O, H-7 eq ), 4.17 6), 579 (11), 551 (6), 477 (54), 455 (23), 397 (12), 283 (16), 221 (20), 216 (25), 199 (26), 196 (28), 139 (35), 78 (100). Iodine (60 mg, 0.24 mmol) and iodobenzene diacetate (69 mg, 0.22 mmol) were added to a 1 : 1 solution of alcohols 14c, 14d (60 mg, 0.10 mmol) in cyclohexane (10 mL).…”

“…The organic layer was washed with brine (10 mL) and dried over anhydrous potassium carbonate. Removal of the solvent under a reduced pressure, followed by flash column chromatography using hexane-diethyl ether (9 : 1) as eluant afforded a 1 : 1 mixture of the title compounds 32c, 32d (54 mg, 90%) as a colourless oil [Found (CI, NH 3 ): MH + , 609.3791; C 36 H 57 O 4 Si 2 requires M r , 609.3795]; m max /cm −1 (CDCl 3 ): 3053,2986,2959,2876,2305,1422,1265,1111,1079,1018,895,736; d H (300 MHz, CDCl 3 ): 0.55 (6H, q, J 8.0, SiCH 2 CH 3 ), 0.84-0.93 (12H, m, Me and SiCH 2 CH 3 ), 1.04 (9H, s, Si t BuPh 2 ), 1.40-2.30 (11H, m, H-1 , H-2 , H-3, H-4, H-4 and H-8), 3.68-3.76 (3H, m, H-7 ax and H-5 ), m,CHOSi,m, CH ax H eq O, H-7 eq ), m,CHO,5.61 (1H,br d,J 10 ,9 11.2,CH=CHCH 2 ,m,CH=CHCH 2 ,m,ArH,m and p),m,ArH,o) 133.98 (quat.,ArSi),134.04 (quat.,ArSi*),135.6 (CH,ArH,o); m/z (CI, NH 3 ): 609 (MH + , 11%), 593 (6), 579 (11), 551 (6), 477 (54), 455 (23), 397 (12), 283 (16), 221 (20), 216 (25), 199 (26), 196 (28), 139 (35), 78 (100). A solution of pyridinium hydrochloride was prepared by bubbling freshly prepared hydrogen chloride gas throug...…”

Inductive and Resonance Effects of Substituents on π-Face Selection

“…On the other hand, the effect of electron-withdrawing substitution of dioxirane on π-face selection in epoxidation of cyclohex-2-en-1-ol derivatives and the unexpected π-face preference of oxaziridinium tetrafluoroborate was attributed to electrostatic stabilization and destabilization of the syn and anti transition states, Scheme 155 …”

Nopol-Based Quinoline Derivatives as Antiplasmodial Agents

“…It is likely that 8 is transported with greater efficiency by PfCRT in the K1 strain and able to engage effectively with a putative cytosolic target, or its transportation out of the food vacuole is significantly hindered in the K1 strain and therefore displayed a more substantial anti-hemozoin effect in the parasite. Synthetic efforts to introduce epoxy and vicinal diol groups to increase aqueous solubility via the unsaturation in the nopol substructure for 1-15 were unsuccessful [21][22][23]. However, 16 was synthesized via epoxidation of nopol followed by esterification reaction with 7-chloro-2-methyl-4-quinolinecarboxylic acid using EDCI and DMAP.…”