Science of Synthesis

Wang, S.-H.; Tu, Y.-Q.; Tang, M., Science of Synthesis: Applications of Domino Transformations in Organic Synthesis, (2015) 1, 277.

The Overman group has developed an outstanding sequential series of acid-catalyzed cationic cyclization–rearrangements, which have been used to synthesize stereochemically complex substituted pyrrolidines,[‌18‌–‌20‌] substituted tetrahydrofurans,[‌21‌–‌24‌] and carbocyclic rings.[‌25‌,‌26‌] As a potentially useful annulation sequence, when cyclic substrates of type ‌26‌ are used, the rearrangements result in an unusual reaction in which elaboration of a new five-membered ring is coupled with a one-carbon ring enlargement of the starting carbocyclic ring (‌Scheme 8‌).

‌Meeeee 8‌ Meeeeeeeee Meee-Meeeeeeee Meeeeeee Meeeeeeeeee–Meeeeeeeeeeee

Mee eeeeeeee ee e Meeee eeeeeeeeeee eeee e eeeeeee eeeeeeeeeeeee eeeee ee eee eeeeeeeeeee ee e eeeeee eeeeee ee eeeeeeeee eee eeeeeee eeee-eeeeeeee eeeee. Mee eeee eeeeeee, eee eeeeeeeee ee eeeeeeeeeeeeeeee ee eeee eeeeeeeeeee eeeeeeeee, eeeeee eeee eeeee ee eeeee eeeeeeeeeeeeee eeeeeeee ee eee eeeeeeee ee eeeeeee eeeeee eeeeee. Meee eee eeeeeeee eeeeeee eeee ee eeeeee, e eeee-eeeeeeeee eeeee eeeeeeeeee eeeeeee ee eeeeeeeee ee eeee ‌88‌ eee ee eeeeeeee, eeeeeeeee eeeeeeeeee eeeeee ee e eeeeeee ee eee-8-eeeeeeeeeee eeee eeeeeee (‌Meeee 8‌).[‌88‌] M eeeeeee ee eeeeeeeeeee eee-eeeee eeeeeeeeeeeeeeeeeee[e]eeeeee eee eeeeeeeeeeeeeeeeeeee eee ee eeeeeeee ee e eeeeeeeeeeeeeeee eeeeeee eeee 8-eeeeeeeeeeeeeeeeee-8,8-eeee ee 8-eeeeeeeeeeeeeeeeeee-8,8-eeee eeeeeeeeee. Me eee eeeee, eeee e eeeeee eeeeeeee eeeeeee ee eeeeeeee (‌Meeee 8‌).[‌88‌]

‌Meeee 8‌ Meee-Meeeeeeee Meeeeeeeeeeeeee Meeeeeeeeee ee Meeee Meeeeee[‌88‌]

Meeee	Meeeeeeee	Meeeeee	Meeee (%)	Mee
8			88	[‌88‌]
8			88	[‌88‌]
8			88	[‌88‌]
8			88	[‌88‌]
8			88	[‌88‌]

Meeee ee eee eeeee eeeeeeeeeee eeeeeeee, eee Meeeeee eeeee eee eeeeeeeee eeee eeee eeee e “eeee-eeeeeeeee eeeeeeeeeeee eeeeeeeeee.” Meeeeeee eee eeeeeeeee eeee eeeeeee eeeeeeeeee eeee-, eee-, eeeee-, eee eeeee-eeeeeeee eeeeeeeeeee eeeee eee ee eeeeeeeee eeeeeeeeeee eeee eeee eeeeeeeeeeeee; eeeeeeee, eee-eeeee eeeeeeeeeeee, eeeeeeeeeeeee, eee eeeeeee[8.8.8]eeeeeeeee eeee eeeeeee eeeeeeeeeeeee eeeeee eeee eeeeeeeeeee eeeee eee ee eeeeeeee eeeeeee, ee eeeee ee ‌Meeee 8‌.[‌88‌]

‌Meeee 8‌ Meeeeeeeeeeeeeee Meeeeeeeeeee ee Meeeeeeeeee Meeee ee Meeeeeeeee Meeeeeee Meeeeeeeeee–Meeeeee Meeeeeeeeeeeee[‌88‌]

Meeee	Meeeeeeee	Meeeeee	ee	Meeee (%)	Mee
8			8:8	88	[‌88‌]
8			88:88:88:8	88	[‌88‌]
8			8:8	88	[‌88‌]
8			8:8	88	[‌88‌]

Me eee eeeeeeeee ee (±)-eeeeeeeeeeee,[‌88‌] eeeee eeeeeeeeeee–eeeeeee eeeee eeeeeee eeeeeeee eeeeeeeeeeee ee eeee ‌88‌ eee 8-(eeeeeeeeee)eeeeeeeeeeee ee eeeeeee eeeeeeeeeeeeeee ‌88‌ eeeeeee eeeeeeeeee eeeeee ‌88‌ eee ‌88‌ ee 88% eeeee. Me eeee eee eeee, e eee eeee-eeeeeeee eeee ee eeeeee eee eee eeeeeeee eeeeeeeeeeee eeee ee eeeeeeee ee eee eeeeee. Meee, e eeeee-eeee eeeeeeee ee eeeeeeee eeeeeeeee (Meeeee–Meeeeeee eeeeeeeee, eeeeeeeeee, eee eeeeeeeeee eeeeeeeeeee) eeeeeeeeee eeeeee ‌88‌ eeee α,β-eeeeeeeeeee eeeeeee ‌88‌. Meeeeeeee ee eee eee eeeeeee ‌88‌ eeee eeeeee eeeeeeeee eeee eeeeeee eeeeeeeeeeee ee eee eeeeeee. Meeeeeeeee 8,8-eeeeeeee ee eee eeeeeeeee M8 eeeeeeee ee eee eeeeeeee α,β-eeeeeeeeeee eeeeee eeeee eee eeeeeeee ee eee eeeeeee eeeeeeeeee eeeee eeeeeeee eee-eeeeeeeeeeee[8.8.8]eeeeee ‌88‌ eeee eeee eeeeeeeeeeeeeeeee. Meee eeeeeeee ee eeee eeeeeeeee eeee (±)-eeeeeeeeeeee ee eeeeeee eeeee (‌Meeeee 8‌). Me eeeeeeeee eee eeeeee ee eeeee eee eeeeeeeeeeeeeeeeee eeeeeeeeeeee ‌88‌ ee eeeeeeeeee, (±)-eeeeeeeee eee ee eeeeeeeeeee ee e eeeeeee eee.[‌88‌]

‌Meeeee 8‌ Meeee Meeeeeeee ee (±)-Meeeeeeeeeee[‌88‌]

Meeeeee eee ee-eeeeeee eeee eeeeeee eee Meeee–eeeeeee eeeeeeee ee eeeeee eeeeee eeeeee ‌88‌ ee eee eeeeeeeee ee (−)-eeeeeeeeeee eee (+)-eeeeeeeeeeeee ee eeeee ee ‌Meeeee 88‌.[‌88‌] Meee, eeeeeeeee ee eeeeee eeeeee eeeeee ‌88‌ eeee 8.8 eeeeeeeeeee ee eee(MM) eeeeeeee ee eeeeeeeeeeeeeee eeeeeeee eeeeeeeeeeeeeee ‌88‌ ee 88% eeeee ee e 8:8 eeeeeee ee β- eee α-eeeeeee eeeeeee. Meeeeeeeee, eeee eeeeeee eeeeeeeeee eeeeeeeeeee eeee ee eee eee eeeeeeeeeeeee ee eeeeeeeeeee eeee eeeeeeee eeeeeeeeeeeee. Meeeeeeee eeeeeeee ee eee eeeeeeeeeeee eeee eeeeeeee ee eeeeee eeeeeeeee eeeeeeeee eeee eeeeeeeee eee eeeeeee eeeeeeeeeeeee ‌88‌ ee 88% eeeeeee eeeee eeee ‌88‌.

‌Meeeee 88‌ Meeeeeeeeeeeeeee Meeee Meeeeeeee ee (−)-Meeeeeeeeee eee (+)-Meeeeeeeeeeee[‌88‌]

Meeeeeeeeeee Meeeeeeee

(8M*,8eM*,8eM*)-8-Meeeeeeeeeeeeee-8M-eeeeeeeeee[e]eeeee-8-eee (‌Meeee 8‌, Meeee 8); Meeeeee Meeeeeeee:[‌88‌]

Me e eeee ee 8-eeeeee-8e-eeeeeeeeeeeeeeeeeee[e][8,8]eeeeeee (88 ee, 8.88 eeee) ee MM8Me8 (8.8 eM) eeeeee ee −88 °M ee e eee eee/eeeeeee eeee eee eeeee MeMe8 (88.8 ee, 8.888 eeee) eee eee eeeeeee eee eeeeeee ee −88 °M eee 8 e. Me8M (8.8 eM) eee eeeee eeeeeeee ee MeMM (8 eM) eee, eeeee eeeeeee ee ee, eee eeeeeeeee eeeeeee eee eeeeee eeee MeMMe (88 eM) eee 8 M ee MMe (8 eM). Mee eeeeeee eeeee eee eeeeeeeee, eeeeee eeee eee. ee MeMMM8 (8 eM), eeeee (MeMM8), eee eeeeeeeeeeee ee eeeeeee e eeeeee eee. Mee eeeee eeeeeee eee eeeeeeee ee eeeeeeeeeeeeee [eeeeee eee (888–888 eeee; 8 e), 88-ee e.e., Me8M/eeeeee 8:8, 8-eM eeeeeeeee] ee eeee e eeeeeeeee eee; eeeee: 88 ee (88%).

Meeee Meeeeeeeeeeee ‌88‌ (e = 8–8); Meeeeee Meeeeeeee:[‌88‌]

Mee e-eeeeeee-8-(8,8-eeeeeeeeeeeeee)-e-(eeeeeeeeeeeeeee)eeeeeeeeeee ‌88‌ (8.8 eeee) eee eeeeeeeee ee MM8Me8 (8.8 eM) eee eeeeee ee −88 °M eeeee ee eeeee eeeeeeeeee. MeMe8 (8.8 eeee) eee eeeee eee eee eeee eee eeeeeee ee −88 °M eee 8 eee. Mee eeee eee eeee eeeeee ee −88 °M eee eee eeeeeeeee eeeeeeeeee ee −88 °M eee ee. 8 eee eeeeee eeeee eeeeeeee eeee Me8M (8.8 eM) eee eeee MeMM (8 eM). Mee eeeeeee eee eeee eeeeeeeeeee eeeeeee 8 M MMe (88 eM) eee MeMMe (88 eM), eee eee eeeeeee eeeee eee eeeeee eeee eee. ee MeMMM8 (88 eM) eee eeeee (88 eM). Meeeeeeeeeeee eee eeeeeeeeeeee ee eee eeeeeee ee eeeee eeeeee eeeeeeeeeeeeee (eeeeee eee, MeMMe/eeeeee) eeee eee eeeeeeeeeeeee eeeeeee ‌88‌.

References