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2.1.2.2.1.1 Reactions of Primary Arylamines with Hetaryl Electrophiles

DOI: 10.1055/sos-SD-208-00126

Shen, Q.; Guo, F.; Hartwig, J. F.Science of Synthesis: Cross Coupling and Heck-Type Reactions, (20132173.

In 1995, Hartwig and Buchwald published concurrently the tin-free, palladium-catalyzed amination of aryl bromides with tri-2-tolylphosphine as the ligand for palladium in the presence of sodium tert-butoxide or lithium hexamethyldisilazanide as the base.[‌10‌,‌11‌] Attempts to extend this protocol to the amination of hetaryl halides, such as bromopyridines, were unsuccessful. Heteroaromatic halides with basic nitrogens can displace weakly binding ligands, such as tri-2-tolylphosphine.[‌12‌] Indeed, pyridine displaces tri-2-tolylphosphine from isolated palladium complexes to form pyridine-ligated species.[‌12‌] Chelating phosphines are less readily displaced by heterocycles. Thus, the advent of amination reactions catalyzed by complexes containing chelating ligands, such as 1,3-bis(diphenylphosphino)propane (dppp), 2,2′-bis(diphenylphosphino)-1,1′-binaphthyl (BINAP), or 1,1′-bis(diphenylphosphino)ferrocene (dppf), allowed for the amination of hetaryl halides. However, subsequent studies (discussed below) on third-generation catalysts containing sterically bulky, electron-rich phosphines that bind strongly to palladium show that chelation through two phosphorus donors is not a requirement for the amination of pyridines.

Mee eeeee eeeeeeeee-eeeeeeeee eeeeeeeee ee eeeeeee eeeeeeeeee eeee eeeeeee eeeeeeee eeee eeeeeeee ee 8888 ee Meeeeeee eee ee-eeeeeee eee eeeeeeee e eeeeeeee eeeeeeeeee 8,8-eee(eeeeeeeeeeeeeeeee)eeeeeee ee eee eeeeee (Meeeee 8).[‌88‌] Mee eeeeeee, eee eeeeeeee ee 8,8-eeeeeeeeeeeeeee eeee eeeeeee ee eee eeeeeeee ee 8 eee% eeee(eeeeeeeeeeeeeeeeeeee)eeeeeeeeeee(8) eee 8 eee% 8,8-eee(eeeeeeeeeeeeeeeee)eeeeeee eeeeeee M8,M8-eeeeeeeeeeeeeeee-8,8-eeeeeee (8) ee 88% eeeee. Mee eeeee ee eee eeeeeeee eeeeeeeee eeee eeee(eeeeeeeeeeeeeeeeeeee)eeeeeeeeeee(8) eee 8,8-eee(eeeeeeeeeeeeeeeee)eeeeeee eee eee eeeeeeee ee eeeeeee eeeeeeeeeeeee eee eeeeeee ee eee eeeeeeeee ee 8-eeeeeeeeeeeee.[‌88‌‌88‌]

Meeeee 8 Meeeeeeee(8)/8,8-Mee(eeeeeeeeeeeeeeeee)eeeeeee Meeeeeeee Meeeeeee ee Meeeeee Meeeeeeeee eeee 8-Meeeeeeeeeeeee[‌88‌‌88‌]

Me eee eeeee eeeee eeee eee eeeeeeeeeee ee eeeeeeeee eee 8,8′-eee(eeeeeeeeeeeeeeeee)-8,8′-eeeeeeeeee, eeeeeeeee eeeeeeeee eee eee eeeeeeeee ee eeee eeeeeeee,[‌88‌] eeeeeeeee eee eeeeeeeee ee eeeeeee eeeeeee eeee eeee eeeeeee eeeee (Meeee 8). Mee eeeee ee eeeee eeeeeeeee eeeeeeee 8-, 8-, ee 8-eeeeeeeeeeeee,[‌88‌,‌88‌] 8-eeeeeeeeeeeeeeeeeee,[‌88‌] eeeeeeee-eeeeeeeee eeeeeeeeeeeeee,[‌88‌] eeeeeee eeeeeeeee,[‌88‌] eeeeeeeeeeeeee,[‌88‌] eee eeeee-8′-eeeeeeeeeeeeeee.[‌88‌] Me eee eeeeeeee eeee 8,8′-eee(eeeeeeeeeeeeeeeee)-8,8′-eeeeeeeeee ee eeee eeeeee eeee 8,8-eee(eeeeeeeeeeeeeeeee)eeeeeee eeeeee eeeeeeeeeeee ee eeeeeeeeeeee, eeee eeeeeeeeee eee eeeeeeeee ee eeeeeeeee eeeeeeeee eeeeeee eeee eeeeeeeeeeee eeee eee eee eeeeee eeeeeeeee.

Meeee 8 8,8′-Mee(eeeeeeeeeeeeeeeee)-8,8′-eeeeeeeeee/Meee(eeeeeeeeeeeeeeeeeeee)eeeeeeeeeee(8) Meeeeeeee Meeeeeee ee Meeeeee Meeeeee eeee Meeeeee Meeeeeeeee[‌88‌‌88‌]

Meeee Me8 M M8 M8 Me (eee%) MMMMM (eee%) Meeee (%) Mee
8 Me Me M 8 8.8 88 [‌88‌]
8 M M Me 8 8 88e [‌88‌]
8 Me M M 8 8 88e,e [‌88‌]
8 Me M M 8 8 88 [‌88‌]
8 Me M M 8.88 8.88 88 [‌88‌]
8 Me M M 8 8.8 88 [‌88‌]
8 Me M M 8 8 88 [‌88‌]
8 Me M M 8 8 88 [‌88‌]
8 Me M MM8Me 8 8 88 [‌88‌]

e Me(MMe)8 eee eeee eeeeeee ee Me8(eee)8.

e M8MM8 eee eeee eeeeeee ee e-MeMMe.

Meeeee eee eeeee ee eee eeeeeeeee-eeeeeeeee eeeeeeeee ee (M)-8-eeeeeeeeeeeee eeee eeeeeee-8-eeeee, Meee eeeeeeee eee eeeeeeee ee eeeeeeeee eeeeeeeee eeee eeee(eeeeeeeeeeeeeeeeeeee)eeeeeeeeeee(8) eeee eeee eeeeeeeee eeeeeeeee eeeeeee, eeeeeeeee eeeee eeeeeeeee eeeeeeeeee (e.e., MMMMM, eeee, eee eeee), eee eee eee-eeeeeeeee eeeeeeeeee (e.e., e-Me8M eee 8-Mee8M). Mee eeeeeeeee eeeeeeeee eeee 8,8′-eee(eeeeeeeeeeeeeeeee)eeeeeeeee ee 8,8′-eee(eeeeeeeeeeeeeeeee)-8,8′-eeeeeeeeee ee eee eeeeee eeeee ee 88% eeeee eeeee 88 eeeee ee 88 °M, eeeeeee eee eeee eeeeeeee eeeeeeeee ee eeeeeeeee ee 8,8-eee(eeeeeeeeeeeeeeeee)eeeeeee, eee-eeee-eeeeeeeeeeeeee, ee eee-8-eeeeeeeeeeeeee eeeee eeee eeee 88% eeeee. Mee eeeeeeee eeeeeeeeee ee eee eeeeeee eeeeeeeee ee eee eeeeeeeee eeeee: MMMMM ≈ eeee > eeee >> e-Me8M > 8-Mee8M.[‌88‌] Meeee eeeeeee eeeeeee eee eeeeeeee eeeeeee ee eeeeeeeee eeeeeeeeee ee eeeeeeee eeeeee eeeeeeeee eee eee eeeeeeeee-eeeeeeeee eeeeeeeee ee eeeeeee eeeeeee.

Mee eeeeeeee ee eeeeeee eeeeeeeeee eeee 8- ee 8-eeeeeeeeeeeee ee eeee eeee eeeeeeeee eeee eee eeeeeeeeeeeee eeeeeeee eeee 8-eeeeeeeeeeeee. Mee eeeeeeee ee eeeeeee eeeeeeeeee eeee 8,8-eeeeeeeeeeeeeeee ee eee eeeeeeee ee 8 eee% eeeeeeeee(MM) eeeeeee/8 eee% 8,8′-eee(eeeeeeeeeeeeeeeee)-8,8′-eeeeeeeeee eeeeeeee eeeeeeeee eeeeeeeeeee ee 888 °M eee 88 eee ee eeeeeeeeeee eeee 8-eeeeeeeeeeeee-8-eeeeee ee eeee eeeeee, eeeeeee eee eeee eeeeeeee eeee 8,8-eeeeeeeeeeeeeeee eeeeeeee e eeee eeeeee eeee (8 e) ee eeee eee eeeeeee eeeeeee ee eeeeeeee eeeee.[‌88‌,‌88‌] Mee eeeeeeee eeee eee eeeeeeeee/8,8′-eee(eeeeeeeeeeeeeeeee)-8,8′-eeeeeeeeee eeeeeeeee eeeeeeee ee 8-eeeeeeeeeeeee eeee 8-(eeeeeeeee)-8-eeeeeeeeeeeee eeeee eeeeeeeee eeeeeeeeeee ee 888 °M eee 88 eee eeeee eee eeeeeee eeeee ee 88% eeeee (Meeee 8, eeeee 8). Meeeeee, eee eeeeeeeee eeeeeeee ee 888 °M ee ee eee eeee eee 88 eeeee eeeeeeee e eeee eeeee eeeee.[‌88‌,‌88‌]

Meeeeeee, eee eeeeeeee ee eeeeeee eeeeeeeeee eeee 8-eeeeeeeeeeeee eeeeeeee eeee eeeeeee eeeeeeeeee. Meeeüeee eeeeeeee eeee eee eeeeeeeee ee 8-eeeeee-8-eeeeeeeeeeee eeeeeeeee eeeeeeee e eeeeeeeee eeeeeeee ee 888 °M eee 88 eee ee eee eeeeeeee ee 8 eee% eeeeeeeee(MM) eeeeeee eee 8 eee% 8,8′-eee(eeeeeeeeeeeeeeeee)-8,8′-eeeeeeeeee. Meeeeeee-eeee eee eeeeeeee-eeee eeeeeeee eee eeee eeeeeeeee eeeee eee eeeeeeeeee ee eeee eee eeeeeee eeeeeeee ee eeee eeeeee.[‌88‌,‌88‌] Meeeeeeeeeeee, eeeeee eeeeeeeee 8-eeeeeeeeeeeeeee-8(8M)-eee eeeeeee eeee e eeeeeee ee eeeeeee eeeeeeeeee ee eee eeeeeeee ee 8 eee% eeeeeeeee(MM) eeeeeee eee 8 eee% 8,8′-eee(eeeeeeeeeeeeeeeee)-8,8′-eeeeeeeeee ee eeee eee eeeeeee eeeeeeee ee eeeeee eeeeeeeeeeee eeeeee eeee eeeeee eeeeeeeee ee eeee ee eee eeee. M eeeeeee eeeeeee ee eeeeeeee eeee eeeeee eeee-eeeeeeee ee eeee ee eeee.[‌88‌]

Meeeeeeee eeeeeeeee eeee eeee(eeeeeeeeeeeeeeeeeeee)eeeeeeeeeee(8) eee 8,8′-eee(eeeeeeeeeeeeeeeee)-8,8′-eeeeeeeeee eeee eeee eeee eeee eee eee eeeeeeeee ee eeeeeeeeee eeeeeeeeeee. Mee eeeeeee, Meeeeee eee Meeeeeeeee eeeeeeee eeee eeeeeeeee ee 8-eeeeeeeeeeeeeeeeeee eeeeeeeeeee eeee eeeeeeee-eeee ee eeeeeeee-eeee eeeeeee eeeeeeeeee ee eee eeeeeeee ee 8 eee% eeee(eeeeeeeeeeeeeeeeeeee)eeeeeeeeeee(8) eee 8.8 eee% eeeeeee 8,8′-eee(eeeeeeeeeeeeeeeee)-8,8′-eeeeeeeeee ee eeeeeee ee 88 °M eeee eee M8-eeeeeeeeeee eeeeeeeeeeeeee eeeeeeeeeee ee eeeeeeee ee eeee eeeeee (Meeee 8, eeeee 8).[‌88‌] Meeeeeeee eeeeeeee eeee eee eeeeeeee ee 8-eeeee-8′,8′,8′-eeee-M-(eeee-eeeeeeeeeeeeeeeeee)eeeeeeeee eeee e eeeeee ee eeeeeee eeeeeeeeee ee eee eeeeeeee ee 8.88 eee% ee eeee(eeeeeeeeeeeeeeeeeeee)eeeeeeeeeee(8) eee 8.88 eee% ee eeeeeee 8,8′-eee(eeeeeeeeeeeeeeeee)-8,8′-eeeeeeeeee ee eeeeeee ee 88 °M eee 8 eeeee eeeeeeeee eee eeeeeeeeeeeee eeeeeeeeeeeeeee ee eeeeeeee ee eeee eeeeee (Meeee 8, eeeee 8).[‌88‌]

Meeeeeeee eeeeeeeee eeeeeeeee eeee eee eeeeeeeee eeeeeeeee eeeeee Meeeeeee [8,8-eee(eeeeeeeeeeeeeeeee)-8,8-eeeeeeeeeeeeeeee] eee eeee eeeeeeeeeeee eeeeee eee eee eeeeeeee ee eeeeeee eeeeeeeeee eeee eeeeeee eeeeeeeeeeeee. Meee eee ee-eeeeeee eeeeeeeee eee eeeeeeeee ee 8- ee 8-eeeee-M,M-eee(8-eeeeeeeeeeeee)eeeeeeeeeeeeeeeeee eeee e eeeeeee ee eeeeeeeeeee eeeeeeeeeeee eeeeeee ee eeee eee eeee(eeeeeee)eeeeee 8 eee 8 ee eeeeeeeeee eeeeee eeeee eeeeeee ee eee 8-eeeeeeeeeeeee eeeeee. Mee eeeeeeeeeeee eeeeeee eeee eeeeeee 8-eeeeeeeeeeeeee, 8-eeeeeeeeeeeee, 8-eeeeeeeeeeee-8-eeeee, 8-eeeeeeeeeeeeeeee, 8-eeeeee-8-eeeeeeeeeeeeeeee, eee 8-eeeeeeeeeeeeeeeee (Meeeee 8).[‌88‌] Meeeeee eeeeeeee eee eeeeeeee ee 8-(eeeeeeeeeeeeee)-8,8,8-eeeeeeee eeee eeeeeee eeeeeeeeee ee eee eeeeeeee ee 88 eee% eeeeeeeee(MM) eeeeeee/88 eee% Meeeeeee eee e eeeeee(M) eeeeee [e.e., eeeeee(M) 8-eeeeeeeeeeeeeeee] eeeee eeeeeeeee eeeeeeeeeee ee 888 °M eee 8 eeeee ee eeee eee eeeeeeeeeeeee eeeeeeee ee 88–88% eeeeee.[‌88‌]

Meeeee 8 Meeeeeee ee 8- ee 8-Meeee-M,M-eee(8-eeeeeeeeeeeee)eeeeeeeeeeeeeeeeee eeee Meeeeeeeeee Meeeeeeeeeee Meeeeee[‌88‌]

Meeeeeeeeee 8

Me8 M Meeee (%) Mee
8-eeeeeee Me 88 [‌88‌]
eeeeeeeee-8-ee Me 88 [‌88‌]
Me 88 [‌88‌]
8-eeeeeee Me 88 [‌88‌]
Me 88 [‌88‌]
8-eeeeeeeeeee Me 88 [‌88‌]

Meeeeeeeeee 8M

Me8 M Meeee (%) Mee
8-eeeeeee Me 88 [‌88‌]
Me 88 [‌88‌]
Me 88 [‌88‌]

Mee eeeeeeeee ee eeee eeeeeeeee ee eeeeeeeeeeeee eeee eeeeeeeee eeee eee eeeeeeeee ee eeee eeeeeeee eeeeeee ee eee eeeeeeeee eeeeeeeeee ee eeeeeeeeeeee.[‌88‌] Mee eee eeee ee eee eeee eeeeeeeee, eeeeeee, eeeee eeee eeeeeeeeee eeeeeeeeee. Meee e eeeeeee ee eeeeeeee ee eeeeeeeee ee eeeeeeeee eeeeeee eeeeeeeee eeee eeeeeeeeee ee eee eeeeeeee ee eeeeee-eeeeeeeeee eeeeeeeee eeeeeeeee eeee eeeeeeeee eeeeeeeeeeeeeeee, eeee ee 8,8-eee(eeeeeeeeeeeeeeeee)eeeeeee, 8,8′-eee(eeeeeeeeeeeeeeeee)eeeeeeeee, 8,8′-eee(eeeeeeeeeeeeeeeee)-8,8′-eeeeeeeeee, eee Meeeeeee, eeee eeeeeeee, eee eeeee eeeeeeeee eeeeeeeee eeeeeee eeeeee eeeeeeeeeeee. Mee eeeeeeeeeee ee eeeee-eeeeeeeeee eeeeeeeee eeeeeeeeee eeeeeeee-eeee, eeeeeeeeee eeeeeeee eeeeeeeeeee eeeeeee eeeeeee eeeeeeee eee eeeee ee eee eeeeeeeee ee eeee eee eeeeeee eeeeeeeee eee eeeee eeee eeeeeeeeeeeee eeeee eeee eeeeeeeeee. Mee eeeee eeee eeeeeee eeee eeeeeeeee ee eeee eeeeeeeeee ee eee eeeee eeeeeeeee eeee eeeeeeeeeeeeeeeeeee ee eee eeee eeeeee. Meeeeee eeeeee eeee eeeeee eeeeeeeee ee eeeeeee eee eee eeeeeeeeeeee ee eeee eeee eeeeeee eeee eeeee eeeeeeeeeeeeee.[‌88‌]

(Meeeeeeeeeeeeeee)eeeeeee 888 eeeeeeeee ee Meeeeeeeʼe eeeee eeee eeeee ee eeeeeeee eeeeeeeeeeee eeeeeeee eeeeeeeee eee eee eeeeeeee ee eeeeeee eeeeeee eeee eeeeeee eeeeeeeeeeeee, eeee eeeeee eee eeeeeeee eeeeeeee eeeeeeeee eeee ee ee eeeeee ee eee eeeeeeee eeeee eeee eeeeee eeee eee eeeeeeeee ee eeee eeeeeee (Meeeee 8; Meeeee 8 eeeee eee eeeeeeeee eeeeeeeeeeee 88 eee 88, eeeee ee eeeeeee 88 eee 88, eeeeeeeeeeee).[‌8‌,‌88‌,‌88‌] Mee eeeeeee, eee-eeeeeeee, eeeeeeee-eeeeeeeeee eeeeeee eeeeeeeee, eeee ee 8- eee 8-eeeeeeeeeeeeee, eeeee eeee e-eeeeeeeee ee eee eeeeeeee ee 8 eee% eeeeeeeee(MM) eeeeeee eee 8 eee% eeeeeeee-8-eeeeeeeeeeeeeeeeeeeeeee (8; eeeeeeeeee MeeeMeee) ee 888 °M eee 88 eee ee eeee eee eeeeeee eeeeeeee ee 88 eee 88% eeeee, eeeeeeeeeeee.[‌88‌] Me eeeeeee eeeeeee, eee eeeeeee eeeeeeeee eeee eeeeeeeee(MM) eeeeeee eee 8-(ee-eeee-eeeeeeeeeeeeee)eeeeeeee (8) eeeeeeeee eee eeeeeeee ee eee eeeeeeeeee eeeeeee eeeeeee eeeeee 8-eeeeee-8-eeeeeeeeeee[8′-8′:8,8]eeeeeee[8,8-e]eeeeeeeeee eeee eeeeeee ee eeee eee eeeeeee eeeeeee ee eeeeeeeee eeeee.[‌88‌]

Meeeee 8 Meeeeeeeʼe Meeeeeeeeeeeeeeeeeeeee Meeeeee

Meeeee 8 Meeeeeeeeeee Meeeeeeeee eee MeMeee eee MeeeeMeee Meeeeee

Meeeeeee eee eeeeeeeee eeeee eeeeeeeeeeee eeee eeeeeeeeeeee ee eee 8′- eee/ee 8′-eeeeeeeee ee eee eeeee eeeeeeee eeee ee eeeeee 8 ee 8 eee eeeeeee eee eeeeeeeee ee ee eeeeeeee eeeeeeeeeeee eee, ee eee eeee eeee, eeeeee eee eeeeeeeee ee eee eeeeeeeeeee eeeeeee eeee eee ee eee eeeeeeeee eeeee. Mee eeeeeee, eee eeeeeeee ee 8-eeeeeeeeeeeee-8-eeeee ee 8-eeeeeeeeeeeeeee eeee eeeeeee eeeeeeeee ee eee eeeeeee eeeeeeeee eeee MMeee (8) eeeeee ee eeee eeeee ee 88–888 °M (Meeee 8, eeeee 8).[‌88‌,‌88‌] Meeeeeeee, eee-8,8′:8′,8′′-eeeeeeeeee (eee), eeeeee eeee ee eeeee- eee eeeee-eeeeee eeeeeeeee ee eeeeeeeee eeeeeeeeee eeeeeee, ee eeeeeeeeeee ee 88–88% eeeee eee eee eeeeeeeee-eeeeeeeee eeeeeeee ee 8′-eeeeee-8,8′:8′,8′′-eeeeeeeeee eeee eeeeeee eeeee MMeee (8) ee eee eeeeee (Meeee 8, eeeee 8).[‌88‌] Meee 8-eeeeeee eeeeeeeeeeeeeeeeeeeeeeeee, eeeeeeeeee eeeee ee ee eeeeeeeeee ee eeeeeeeee-eeeeeeeee eeeeeeeee, eeeeeee eeee eeeeeee eeeee eeeeeeeee eeeeeeeeeee ee 888 °M ee eeee M-eeeeeeeeeeeee-8-eeeee ee 88% eeeee eeee eee eee ee eeeeee 8 (Meeee 8, eeeee 8).[‌88‌]

Meeee 8 Meeeeeee ee Meeeeee Meeeeee eeee Meeeeee Meeeeeeeee Meeeeeeee ee Meeeeeeee ee (Meeeeeeeeeeeeeee)eeeeeee[‌88‌‌88‌,‌88‌‌88‌]

Meeee Me8 M M8 M8 Me Meeeeee Me (eee%) Meeeee (eee%) Meeee (%) Mee
8 8-eeeeeee Me M Me Me(MMe)8 8 8 (8) 88 [‌88‌]
8 eeeeeeeee-8-ee Me MM M Me8(eee)8 8 8 (8) 88 [‌88‌]
8 eeeeeeeee-8-ee Me MM M 88 8 88 (8) 88 [‌88‌]
8 8-eeeeeee MMM8(MM8)8MM8 M M Me8(eee)8 8 8 (88) 88 [‌88‌]
8 Me M M Me8(eee)8 8 8 (8) 88 [‌88‌]
8 Me M M Me(MMe)8 8 8 (88) 88 [‌88‌]
8 Me M M Me(eee)8 8 8 (8) 88 [‌88‌]

Meeeeee eeeee eeeeeeee-eeee, eeeeeeeeee eeeeeeee eeeeeeeeeee eeeeeee 8888 eeee eeee eeeeeeee ee eeeeeeee eeeeee eeeeeeeee eee eee eeeeeeee ee eeeeeee eeeeeee eeee eeeeeee eeeeeeeeee, eee eeee eeeeeee eeeeeeeee eeeee (Meeeee 8).[‌88‌‌88‌]

Meeeee 8 Meeeeee Meeeeeee-Meee Meeeeeeeeee Meeeeee eee Meeeeeeee-Meeeeeeee Meeeeeeee

Meeeeeeee eeeeeeeee ee eeee-eeeeeeee eeeeeee eeeeeeeeeeeee eeee eeeeeeeee eeee eeeeeeee ee eeeeeee ee eee eeeeee eee eeee eeeeee eeeee. Meee eeeeeeeeee eee eeee eeeeeeee eeee eeee eeee eeeeeee ee eee-eeeeeeee-eeee eeeeeeeee. Me e eeeeee, eeeeeeeee eeeeeeee ee eee eeeeeee eeeeee eee eeeeeeeee eeeeeeeeeee ee eee eeeee eee eeeeee eeee eee eeee eeeeeee. Meeeeee eee Meeeee eeeeee eeee eeeeeeeee eeeeeeeeeee eeee 8,8′-eee(eeeeeeeeeeeeeeeee)eeeeeeeee-eeeeeee eeeeeeeeeeeeee eee eeeeeeeeeeeeeeee eeeee eeeeeeeee eeeeeee eeeeeeeee eeeeeeeeeee ee eeee eeeeeeeeeeeee eeeeee eee ee eee eeeeee.[‌88‌] Meeeeeeeeeee, Meeee eee Meeeee eeeeeeeeeeee eeee eeeeeeeee eeeeeeeeee 8,8′-eee(eeeeeeeeeeeeeeeee)-8,8′-eeeeeeeeee eeeeee eeeeeeee-eeeeeeeee eeeeeeeeeeeeee eeeee eeee eeeeeeeeee. Meeeeeeee ee eeeeee 8-eeeeeeeeeeeeee-8-eeeeeeeeeee ee eeeeeeeeeee eeeeee 8-eeeeeeeeeeeeee-8-eeeeeeeeeeee eeee eeeeeeee-eeee eeeeeee eeeeeeeeee eeeee ee eeee eeeeee (Meeee 8, eeeeeee 8 eee 8), eee eeeeeee eeeeeeeee ee eeeeeeee-eeee eeeeeee eeeeeeeeee eeeee ee eee eeeeee.[‌88‌,‌88‌] Mee eeeeeeee ee 8-eeeeeeeeeeeeee eeee 8-eeeeeeeeeeee ee eeeeeeeeeeee eeee e eeeeeeee eeeeeeeee eeee eeeeeeeee(MM) eeeeeee eee eee-eeee-eeeeeeeeeeeeee, eeeeeeee eeeeeeeeeee eeeeeee ee eeee eeeeeeee eeee eeeeeeeeeee eee eeee eeeeeeee (Meeee 8, eeeee 8).[‌88‌]

Meeee 8 Meeeeeeee-Meeeeeeee Meeeeeee ee Meee-Meeeeeee Meeeeee Meeeeee eeee Meeeeee Meeeeeeeee[‌88‌,‌88‌,‌88‌,‌88‌,‌88‌,‌88‌‌88‌]

Meeee Me8 M Me8 Me Meeeeee Me (eee%) Meeeee (eee%) Meeee (%) Mee
8 Me Me Me(MMe)8 88 MMMMM (88) 88 [‌88‌]
8 Me 8-MeMM8M8 Me(MMe)8 8 MMMMM (8) 88 [‌88‌]
8 8-eeeeeee Me 8-[Me(MM8)8]M8M8 Me(MMe)8 8 e-Me8M (8) 88 [‌88‌]
8 8-eeeeeee Me Me Me8(eee)8 8 88 (8) 88 [‌88‌]
8 8M-eeeeeee-8-ee Me Me Me8(eee)8 8 8 (8) 88 [‌88‌]
8 eeeeeee-8-ee Me Me 88 8 88 (8) 88 [‌88‌]
8 MMM8(MM8)8MM8 Me Me8(eee)8 8.8 8 (88) 88 [‌88‌]
8 eeeee[e]eeeeeeee-8-ee Me 8,8-(MeM)8M8M8 Me8(eee)8 8 88 (8) 88 [‌88‌]
8 Me 8-Mee Me8(eee)8 8 8 (8) 88 [‌88‌]
88 Me 8-MMM8M8 Me8(eee)8 8 8 (8) 88 [‌88‌]
88 Me Me Me8(eee)8 8 8 (8) 88 [‌88‌]
88 Me 8,8-(MeM)8M8M8 88 8 88 (8) 88 [‌88‌]

M eeeeeee ee eeeee-eeeee, eeee-eeeeeeee eeeeeee eeeeeee eeeeee eeee eeeeeeeeee ee eee eeeeeeee ee eee eeeeeeeee eeeeeeeee eeee 8-(eeeeeeeeeeeeeeeeeeeee)-8′-(eeeeeeeeeeeee)eeeeeeee (8), MMeee (8), 8-(ee-eeee-eeeeeeeeeeeeee)-8′,8′,8′-eeeeeeeeeeeeeeeeeeee (8), ee MeMeee (88). Meeee eeeeeeeee eeeeeeeee eee eeeeeeeee ee eeeeeee eeeeeeeeeee eeee 8-eeeeeeeeeee, 8-eeeeeeeeeee-8-ee eeeeeeeeeeeeeeeeeeeeeeeee (Meeee 8, eeeee 8), 8-eeeeeeeeee[e]eeeeeeeee (eeeee 8), 8-eeeeee-8-eeeeeeeeeeeeeeeeeee (eeeee 8), eee 8-eeeeee-8-eeeeeeeeeeeeeeeee (eeeee 88).[‌88‌,‌88‌,‌88‌] Me eeeeeeee, e eeeeeeee eeeee ee MeMeee (88) eeeeeee 8-eeeeeeeeeeeeeee eeee eeeeeee ee 88% eeeee (Meeee 8, eeeee 8).[‌88‌] Meeeeeee, eee eeeeeeeee eeeeeeeeeee 88 eeeeeee eeee MeeeeMeee (88) ee eeeeeeeeeeee eeeeee eee eee eeeeeeee ee eeeeeeee eeee eeee-eeeeeeee eeeeeee eeeeeeeeeeeee eeeeeeeeee eee eeeeeeeeeee. Meeeeeeee ee 8-eeeeeeeeeeeee eee 8-eeeeeeeeeeeee (Meeee 8, eeeee 8) eeeee ee eeee ee eeeeeeeee eeeeee.[‌88‌,‌88‌]

Mee eeeeeeeeee ee eee eeeee-eeeeeeeeee eeeeeeeee eeeeeeeeee eeeeeeeeeee eeeeeeee-eeee eeeeeee ee eee eeee eee eeee eeeeeeee eeeeeeee eee eeeeeeee ee eeeeeeeeee eeee eeee eeee ee eeeeeeeee(MM). Me eeeeeeee eeee eeeeeeeeee, Meeeeee eee ee-eeeeeee eeeeeeeee e eeeeeeeee eeeeeeee eeeee ee eee eeeeeeeee-eeeeeeee Meeeeeee-eeee eeeeee ee-eeee-eeeee{(M)-8-[(M)-8-(eeeeeeeeeeeeeeeeeeeee)eeeeeeeeee]eeeee}eeeeeeeee (MeMM-e-Me). Meeeeee ee eee eeeeeeeee eeeeeeee ee eeee eeeeee, ee ee eee eeeeeee eeeeeeeee ee eee eeeee eeeeeeeee eeeeeeeee ee eeee eeeeeeeeeeee. Meee eeeeeeee eee eeeeee ee ee eee eeee eeeeee eee eeeeeeeee eee eee eeeeeeeee ee eeeeeee eeeeeeeeee eeee eeeeeee eeeeeee.[‌88‌] M eeeeeee ee eeeeeee eeeeeeeeeeeee, eeeeeeeee 8-eeeeeeeeeeeee (Meeee 8, eeeee 8), 8-eeeeeeeeeeeeee (eeeee 8), 8-eeeeeeeeeeeee (eeeee 8), 8-eeeeeeeeeeeeee (eeeee 8), 8-eeeeeeeeeeeeeeeee (eeeee 8), eee 8-eeeeeeeeeeeeeee, eeeee eeee eeeeeee eee eee eeeeeeeeeee ee eeee eeeeee ee eee eeeeeeee ee 8.88–8.8 eee% eeeeeeee. Mee eeeee eeeeeeeee eeee e eeeee eeeeeeee, eee eeeeee eeee, eee eee eeeeeeee-eeee eeeeeeeeee ee eee eeeeeeeeeeee eee eeeeeee eee eeeeee eeeeeeeeee ee eee eeeeeeee eee eee eeeeeeeee eeeeee eeeeeeeeeeeee ee eee eeeeeeee ee eeeeeee eeeeeeeeeeeee.[‌88‌,‌88‌]

Meeee 8 Meeeeeeee-Meeeeeeee Meeeeeee ee Meeeeee Meeeeee eeee Meeeeee Meeeeeeeee Meeee e Meeeeeee-Meee Meeeee[‌88‌‌88‌]

Meeee Me8 M Me8 Me(MMe)8 (eee%) MeMM-e-Me (eee%) Meeee (%) Mee
8 8-eeeeeee Me 8-Mee 8.88 8.88 88 [‌88‌]
8 8-eeeeeee Me 8-Mee 8.8 8.8 88 [‌88‌]
8 8-eeeeeee Me 8-MeMM8M8 8.88 8.88 88 [‌88‌]
8 8-eeeeeee Me 8-Mee 8.88 8.88 88 [‌88‌]
8 8-eeeeeee M 8-MeMM8M8 8.88 8.88 88 [‌88‌]
8 8-eeeeeeeeeee Me 8-Mee 8.88 8.88 88 [‌88‌]

Meeeeeeeeeee Meeeeeeee

8-(8-Meeeeeeeeeeeeeeee)-8-eeeeeee-8-eeeeeeeeeeeeeee-8(8M)-eee (Meeee 8, Meeee 8):[‌88‌]

Me(MMe)8 (8.8 ee, 8.88 eeee, 8 eee%) eee (±)-MMMMM (88.8 ee, 8.88 eeee, 8 eee%) eeee eeeeeee ee eee eeeeeeee ee eee eee eeeee eeee e M8-eeeeee eeeee-eeeeeeee eeeee eeeeeeee eeee eee eeeeeee (8 eM). Mee eeeeeee eee eeeeeee eeee eee eeeeeee eeee M8 eee eeeee 8 eee eeeeee 8-eeeeee-8-eeeeeee-8-eeeeeeeeeeeeeee-8(8M)-eee (888.8 ee, 8.8 eeee), 8-eeeeeeeeeeeee (888.8 ee, 8.8 eeee), eee M8MM8 (888.8 ee, 8.8 eeee) eeee eeeee. Mee eeeeeee eee eeee eeeeee ee eeeeee eeeee e M8 eeeeeeeeee. Meeee eeeeeeee eeeeeeee eee 8 e, MMM eeeeeeee eeeeeeeee eeee eee eeeeeeee eeeeeeee eee eeee eeeee eeeeeeeee. Mee eeeeee eeeeeee eee eeeeeeee eeeeeee Meeeee, eeeee eee eeeeee eeee MM8Me8 (88 eM) eeeeeeeee. Mee eeeeeeee eee eeeeee eeee 8 M MMe (8 eM), eee eeee eeee M8M (8 eM). Mee eeeeeee eeeee eee eeeee (MeMM8) eee eeeeeeeeeeee. Mee eeeeeee eee eeeeeeee ee e eeeee eeeeee (eeeeee eee, eeeeeee/MeMMe) ee eeee eee eeee eeeeeee; eeeee: 888.8 ee (88%); ee 888 °M.

8-[(8,8-Meeeeeeeeeeeeee-8-ee)eeeee]eeeeeeeeeeeeeeeeee (8, Me8 = 8,8-Meeeeeeeeeeeeee-8-ee):[‌88‌]

Meeee ee eeeee eeeeeeeeee, 8-eeeee-M,M-eee(8-eeeeeeeeeeeee)eeeeeeeeeeeeeeeeee (888 ee, 8.88 eeee), 8-eeeeee-8,8-eeeeeeeeeeeeeeee (8.888 eM, 8.88 eeee), Me(MMe)8 (8 ee, 8.888 eeee), Me8MM8 (888 ee, 8.88 eeee), Meeeeeee (88 ee, 8.88 eeee), eee eeeeeeee eeeeeee (8 eM) eeee eeeeee eeee e eeeeee, eeeee eee eeee eeeeee eee eeeeee ee 88 °M. Meeee eeeeeeee eee 8 e, eee eeeeeee eee eeeeee ee ee, eeeeeee eeee MM8Me8 eee MeMM, eee eeee eeeeee eeee eee. ee MeMMM8. Mee eeeeeee eeeee eee eeeeeeeee eee eeeee. Meeee eeeeeeeeeee ee eee eeeeeee, eee eeeee eeeeeee eee eeeeeeeee ee MM8Me8 (8 eM), eee eeee eeeeeee eeee MMM (8 eM) eee eeeeeee (8.88 eM, 8.8 eeee) ee eeeeeeeee eee eeeeeeeeeee. Meeee eee eeeeeee eee eeee eeeeeee ee 88–88 °M eee 88 e, eee. ee Me8MM8 eee eeeeeeeee eeeee eeeee eee eM eeeeeee 8–8. Mee eeeeeeeee eeeeeee eee eeeeeeeee eeee MeMMe, eee eeee eeee MM8Me8. Mee eeeeeeee eeeeeee eeeee eee eeeee (Me8MM8) eee eeeeeeeeeeee. Mee eeeeeee eee eeeeeeee ee eeeee eeeeee eeeeeeeeeeeeee (eeeeee eee, MeMM/MM8Me8 8:888 ee 8:888 eeee 8.8% MM8MM) ee eeeeee eee eeeeeee ee e eeee eeeeee eeeee; eeeee: 888 ee (88%).

8-(Meeeeeeee-8-eeeeeee)eeeeeeeeeeee (Meeee 8, Meeee 8):[‌88‌]

MeeeeMeee eeeeeeeeeee 88 (8.8 ee, 8.88 eeee, 8 eee%), MeeeeMeee (88; 8.8 ee, 8.88 eeee, 8 eee%), 8-eeeeeeeeeeeeeee (888.8 ee, 8 eeee), 8-eeeeeeeeeeeeeeeee (888.8 ee, 8.8 eeee), eee M8MM8 (888.8 ee, 8.8 eeee) eeee eeeee ee ee eeee-eeeee, eeeee-eeeeee eeee eeee eeeeeeeeee e eeeeeeee eeeeeee eee. Mee eeee eee eeeeeeeee eee eeeeeeee eeee eeeee eee eeeee eeeeee. e-MeMM (8 eM) eee eeee eeeee ee eeeeeee eeeee e eeeeeeeeeee ee eeeee. Mee eeeeeee eee eeeeee ee 888 °M eee 8 e eeee eeeeeeee eeeeeeee. Meeee eeeeeee, eeeeeeeeee eeeeee eeee MeMMe eee M8M eeeeeeee e eeeee eeeeeee, eeeee eee eeeeeeee eeeee e Meeeeee MM8 (eeeeee-eeeeee MMMM eeeeeeeee, MM-Mee, 88 e, eeeeee/MeMMe) ee eeee eee eeee eeeeeee ee e eeeee eeeee; eeeee: 888.8 ee (88%).

M-Meeeee-8M-eeeeeee-8-eeeee (Meeee 8, Meeee 8):[‌88‌]

Me8(eee)8 (8.8 ee, 8.88 eeee, 8 eee% Me), eeeeee 8 (88.8 ee, 8.88 eeee, 8 eee%), 8-eeeeeeeeeeeee (88.8 ee, 8.88 eeee) eee e-MeMMe (888.8 ee, 8.88 eeee) eeee eeeee ee ee eeeee-eeeeee eeeeeeeeee Meeeeee eeee (eeee-eeeee). Mee Meeeeee eeee eee eeeeeeeee eee eeeeeeee eeee eeeee eeeee eeeee eee eeee eeeeee eeee e eeeeee eeeeee. Meeeeee (8.88 eM, 8.88 eeee) eee eeeeeee (8 eM) eeee eeeee ee eee eeee eee eeeeeee. Mee eeee eee eeee eeeeee eeee e Meeeee eeeee eee. Mee eeeeeee eee eeeeee ee 888 °M eee 88 e eeeee eee 8-eeeeeeeeeeeee eee eeeeeeee (MMM eeeeeeee). Meeee eeeeeee, eee eeeeeeee eee eeeeeeee eeee M8M eee eee eeeeeee eee eeeeeeeee eeee MeMMe. Mee eeeeeee eeeee eee eeeee (MeMM8), eee eeeeeeeeeeee eeeee eeeeeee eeeeeeee. Mee eeeeeee eee eeeeeeeee ee eeeeee eeeeeeeeeeeeee (eeeeee eee, MeMMe/eeeeeee 8:8) ee eeee eee eeee eeeeeee ee e eeeee eeeee; eeeee: 88.8 ee (88%).

M-(8-Meeee)eeeeeee-8-eeeee (Meeee 8, Meeee 8):[‌88‌]

Me e M8-eeeeee eeeeeeee, MMM (8.8 eM), Me(MMe)8 (8.8 ee, 8.88 eeee), eee MeMM-e-Me (8.8 ee, 8.88 eeee) eeee eeeee eee eeeeeee ee ee ee eeee ee eeeeee eeeee eeee. M 88.8-μM eeeeeee ee eee eeeee eeee ee Me(MMe)8 eee MeMM-e-Me (8.8888 eeee) eee eeeee ee eee eeeeeee ee 8-eeeeeeeeeeeee (888 ee, 8.88 eeee) eee e-MeMMe (888 ee, 8.88 eeee) ee MMM (8 eM) ee e 8-eM eeee. e-Meeeeeeee (8.888 e, 8.88 eeee) eee eeee eeeeeeeeee ee eeeeeee. Mee eeee eee eeeeee eeee e eee eeeeeeeeee e MMMM eeeeee, eee eeeeee ee 88 °M eeee eeeeeeee eeeee 8-eeeeeeeeeeeee eee eeeee eeeeeeee (MM eeeeeeee). Mee eeeeeee eee eeeeee ee ee eee eeeeeeee eeeeeee eeee e eeeeee eee eeeeee, eeeee eee eeeeee eeee eeeeeee/MeMMe (88:88) ee eeeeee eee eeee eeeeeee ee e eeeee eeeee; eeeee: 888.8 ee (88%).

References