Science of Synthesis

Alberti, M. N.; Tzirakis, M. D.; Orfanopoulos, M., Science of Synthesis, (2009) 38, 475.

The 2,3-dioxabicyclo[3.3.1]nonane system was first identified in the naturally occurring antimalarial, yingzhaosu A.[‌16‌] This system is readily available by a useful method based on the adaptation of the thiol–alkene co-oxygenation (thiol–olefin co-oxygenation, TOCO) reaction.[‌17‌] The title reaction is initiated by 2,2′-azobisisobutyronitrile and ultraviolet irradiation or by di-tert-butyl peroxalate. In this four-component, one-operation, free-radical domino reaction, five new bonds are sequentially formed. Thus, (R)-(+)-limonene [(R)-‌20‌], the related compounds (S)-‌23‌, or a phenyl analogue of (R)-(+)-limonene ‌26‌ in the presence of triplet dioxygen, a thiol, and 2,2′-azobisisobutyronitrile or di-tert-butyl peroxalate (catalytic amount) afford endoperoxide–hydroperoxides ‌21‌, ‌24‌, or ‌27‌, respectively (‌Scheme 6‌).[‌18‌,‌19‌] These products are chemoselectively reduced with triphenylphosphine to give the more stable hydroxy endoperoxides ‌22‌, ‌25‌, or ‌28‌, respectively. β-Hydroxy peroxides generated by co-oxygenation of 3-methylbut-3-en-1-ol (‌29‌) can be condensed in situ with ketones, to afford functionalized 1,2,4-trioxepanes ‌30‌ in good yields (‌Scheme 6‌).[‌20‌]

‌Meeeee 8‌ Meee-Meeeeee Meeeeeee Meeeeeeee Meeee–Meeeee Me-eeeeeeeeeee[‌88‌–‌88‌]

‌Meeeeeeeeee 8M‌

‌Meeeeeeeeee 8M‌

e Meeeeee M eee M eeee eeeeeeeeeee eee eeee eeeeeee.

Meeeeeeeeeee Meeeeeeee

(8M)-8,8-Meeeeeee-8-[(eeeeeeeeeeeeee)eeeeee]-8,8-eeeeeeeeeeee[8.8.8]eeeee-8-ee (‌88‌, M8 = Me); Meeeeee Meeeeeeee:[‌88‌]

Meeeee M: M8 eee eeeeeee ee ee eeeeeee e eeeeeeeeee eeeeeee eeee ee (M)-‌88‌ (8.88 e, 88 eeee, 8 eeeee) eee ee-eeee-eeeee eeeeeeeeee (888 ee, 8.88 eeee, 8.88 eeeee) ee eeeeeee/eeeeeee (8:8; 888 eM) (MMMMMMM: eeeeeeeeee) eeee eeeeeeeeeeee eeeeeeee ee MeMM (8.88 e, 88 eeee, 8 eeeee) ee eeeeeee (88 eM) eeee e eeeeee ee 88 e (eeeeeee eeee). Meeee eee eeeeeeee ee eeeee eee eeeeeeeee, eee eeeeeee eee eeeeee ee 8–8 °M, eeeeeee eeee eeeee, eee eeeeeee eeee MM8Me8 (888 eM), eee eeee eeeeeeee Me8M (8.88 e, 88 eeee, 8 eeeee) eee eeeee. Mee eeeeeee eee eeeeeee eee ee eeeeeeeeee 8 e ee 8–8 °M, eeeeeeee ee 8 e ee ee, eee eeee eeeeeeeeeeee ee ee. Meeee eeeeeeeeeeeeee (eeeeee eee, eeeeee/MeMMe 88:8 ee 8:8) eeeeeeee eee eeeeee eeeeee eeeeeee eeeeeeeeeeee ‌88‌ (M8 = Me) ee e eeeeeee ee eeeeeeeeeeeee; eeeee: 8.88 e (88%).

(8M)-8,8-Meeeeeee-8-[(eeeeeeeeeeeeee)eeeeee]-8,8-eeeeeeeeeeee[8.8.8]eeeee-8-ee (‌88‌, M8 = Me); Meeeeee Meeeeeeee:[‌88‌]

Meeeee M: M eeee ee (M)-‌88‌ (8.88 e, 88 eeee, 8 eeeee) eee MMMM (88 ee, 8.88 eeee, 8.88 eeeee) ee MeMM (888 eM) eee eeeeee eeee e Meeee, eeeee-eeeeee, eeeee-eeeeeeee eeeee eeeeeeee eeee ee eee-eeeeee eeeeeeee eeeeeee eee. Mee eeeeeee eeee ee eee eeeeeeee eeeee eee eeeeeeeee ee e eeeee eeeeeeee eeeeeeeee eeeeeeeee eeeeee eeee M8 eee eeeeee eeee eee eeeeee eeeeeee e eeeeeeee eeee ee e eeeeeeee eeee eeeeee eeee eeeee. Mee eee eeee eeeee ee eee eeeeeeee eeeee eeee eeeeeeee eeee eeeee. Mee eeeeeeee eeeeee eee eeeeeeeeee eeeeeee eeee e eeeee eeeeeeee eeeeeeee ee eeee M8. Meee, eee eeeeeee eee eeeeeeeeee eeeeeee eee MM eeeeeeeeee (eeee e eeeeeeee ee 8–8 ee) ee 8 °M eeee eeeeeeeeeeee eeeeeeee ee eeeee ee MeMM (8.88 e, 88 eeee, 8 eeeee) ee MeMM (88 eM) eee MMMM (88 ee, 8.88 eeee, 8.88 eeeee) ee MeMM (88 eM) eeee e eeeeee ee 88 e (eeeeeee eeee). Meeee eeeeeeeeee ee eee eeeeeeee, eee eeeeeee eee eeeeee ee ee eeeeeeeee eeeee (Meeeee M) ee eeeee eeeeeee eeeeeeeeeeee ‌88‌ (M8 = Me) ee e eeeeeee ee eeeeeeeeeeeee; eeeee: 8.88 e (88%).

8′-{[(8-Meeeeeeeeeee)eeeeeeee]eeeeee}-8′-eeeeeeeeeee[eeeeeeee[8.8.8.88,8]eeeeee-8,8′-[8,8,8]eeeeeeeeee] (‌88‌, Me8 = 8-MeM8M8; M8,M8 = Meeeeee[8.8.8]eeeeee-8,8-eeee); Meeeeee Meeeeeeee:[‌88‌]

M eee-eeeeee, 888-eM, eeeee-eeeeeeee eeeee eee eeeeeee eeee e eeee ee 8-eeeeeeeee-8-ee-8-ee (‌88‌; 8.8 e, 8.8 eeee) eee MMMM (88.8 ee, 8.88 eeee) ee MeMM (888 eM). Mee eeeeeeee eeeeee eee eeeeeee eeee M8 eee eeeeeee eee ee 8 °M eee eeee eeeeeeeee eee eeee eeeee e eeeeeeee eeeeeeee ee eeee M8, eeee eee eee ee eee M8 eeeeeeee. Mee eeeeeee eee eeeeeeeeee eeeeeee eee MM eeeeeeeeee ee 8 °M eeeee ee eeeeeeeeee eeeeeee 888-M, Meeee-Mee MM eeee ee e eeeeeeee ee 8–8 ee, eeee eee eeeeeeeeeeee eeeeeeee ee 8-eeeeeeeeeeeeeeeeee (8.88 e, 8.88 eeee) ee MeMM (88 eM) eeee e eeeeee ee 88 eee. Meeee eeeeeeeeee ee eee eeeeeeee, eee eeeeeee eee eeee ee eeeeeeee eeeeeeee ee 8 °M, eee 8–8 e ee eeeee eeeeeeeeeee ee eeeeeeee eeeeeeeee (eeeeeeeee ee MMM). Mee eeeeeeee eeeeee eee eeee eeeeee ee −88 °M eee eeeeeee eeee M8, eee e eeee ee eeeeeeeee-8-eee (8.88 e, 88.88 eeee) ee MM8Me8 (88 eM) eee eeeee, eeeeeeee ee e eeeeeeeee eeeeee ee MeMM (88 ee, 8.88 eeee). Mee eeeeeee eee eeee eeeeeeee ee −88 °M eee eeeeeee ee eeee eeeeee ee ee eeeeeeeee. Mee eeeeeee eee eeeeeeeeee eee eee eeeeeee eee eeeee eeeeeeeeeeeeeee (eeeeee eee) ee eeee e eeeeeeeee eeeee; eeeee: 88%; ee 88–88 °M.

References