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Please login or sign up for a free trial to access the full content. Hydroformylation Using Phosphine Ligands

DOI: 10.1055/sos-SD-201-00223

van Leeuwen, P. W. N. M.Science of Synthesis: Stereoselective Synthesis, (20111417.

The use of the classic triphenylphosphine-based rhodium hydroformylation catalysts in organic synthesis is limited due to the moderate regioselectivity that is obtained; for unhindered alk-1-enes the ratio of linear to branched product is roughly 2:1, and additionally the alkene substrate may be converted into internal alkenes (20atm, 70100°C, [Rh]=1 mM, [Ph3P] <10 mM). Isomerization to internal alkenes may vary from very low to almost complete depending on the conditions applied; low carbon monoxide partial pressure, high temperature, and low triphenylphosphine concentration lead to more isomerization. At high triphenylphosphine concentrations the linearity increases, but higher pressures and temperatures are required to obtain acceptable rates, as in the commercial process for propene hydroformylation to butanal (30atm, 120°C, 94% linear product, TOF=300mol·mol1·h1). For substituted alkenes, however, triphenylphosphine may present a useful catalyst as is shown in a series of model substrates in Scheme 7.[‌52‌] In this series only steric effects are the cause of the change in selectivity, which suggests that with Xantphos and BISBI catalysts also, and the commercial system using triphenylphosphine, steric effects are responsible for the selectivity. The order in alkene concentration of the reaction rate is found to be 1 for all substrates, demonstrating the normal behavior for triphenylphosphine and alk-1-enes under these conditions. Electronically modified alkenes, such as styrene and acrylates, may give preferential formation of branched products due to an electronic effect in the rate of the insertion step or in the stabilization of an alkylrhodium intermediate. Hydroformylation of internal alkenes or 2,2-dialkyl-substituted ethenes is slow and thus this is not a useful reaction. Formation of internal alkenes during terminal alkene hydroformylation does not lead to hydroformylation of internal alkenes either when triphenylphosphine-based catalysts are used, and the isomerization products can and must be separated from the reaction mixture.

Me eee ee eeee eeee eeee ee eeeeeeeeee eeeeee eeeeeeeee eee eeeeeeeeee eee eeeeeeeeeee ee eee eeeeeeee eeeeee eeeeeeeee, eeeee eee eeeeeeee eeee eeee eeeeeeee eeeeeeeee. Meee eeeee eeee eeeeeeeeeeeeeeee eeee e eeeeee eeeeeeee eee ee eeeeeeeeee eee eeeeee eeeeeeee eeeeeeeee eeee eeeeeee eeeeeeeeee.

Meeeee 8 Meeeeeeeeeeeeeee ee Meeeeee Mee-8-eeee eeee e Meeeeeeeeeeeeeeeee-Meeeeeee Meeeeee Meeeeeee[‌88‌]

Meeeeeeeeee 8

M8 Meeeeee Meee (eee·eee8·e8) Meeeee (%) ee Meeeee Meeeeeee Mee
Me 8888 88.8 [‌88‌]
Me 88888 88.8 [‌88‌]
(MM8)8Me 8888 88.8 [‌88‌]
eMe 8888 88.8 [‌88‌]
MM8e-Me 8888 88.8 [‌88‌]
MM8e-Me 8888 88.8 [‌88‌]
e-Me 8888 88 [‌88‌]
MMMeMe 8888 88.8 [‌88‌]
MMe8Me 8888 88 [‌88‌]

e Meeeee eeeeeeeee eeeeeeeeeeeee=88eeee ee 88eM ee eeeeeee. Me eeeeeeeeee eeeeeee eee eeeeeeee. Meeeeeeee ee eee eeeeeeee eeeeeeee.

Meeeeee eeeeeeeee eeeeeeeeee eeee ee eeeeee eeeeee eeeeeee, e.e. 88, ee eee eeeeeeeeeeeeeeee ee eeeeeeee eeeeeee eeeeeee ee eee eeee-eeeee eeeeee (Meeeee 8).[‌88‌] Meeeeee eeeeeeeeeeee eeee ee eee eeee (eee Meeeeee Mee eeeeeeeeeeee eeeeeeeee eeee eeeeeee eeeeeee eeee eee eeeeeeeeeeee eeeeeeeee (eeee Meeee), eee eeee eeeeeee eeeeee eeeeeee eeeeeee eeee eeee eeeeeeee eeeee eee eeee 8888e.[‌88‌,‌88‌]

Meeeee 8 Meeeeee eee eee Meeeeeeeeeeeeeee ee Mee-8-eee[‌88‌]

Meeeeeeeeee 8

Meeeeee βee (°) Meeeeeeeeee Meeee (°) MMMe (eee·eee8·e8) Meeeeee Meeee (Meeeee/Meeeeeee) Meeeee Meeeeeee 88 (%) Meeeeeeeeeeeee (%) Mee
MMMeeee 888 88888 888 8.8:8 88.8 8 [‌88‌]
Meeeeeeeee 888 88888 888 88:8 88.8 8 [‌88‌]
Meeeeeeeeee 888 88888 888 88:8 88.8 8.8 [‌88‌]
Meeeeeee 888 88888 888 88.8:8 88.8 8.8 [‌88‌]
MMMeeee 888 888888 888 8:8 88 8.8 [‌88‌]
MMMMM 888 888888 888 88.8:8 88.8 8.8 [‌88‌]

e [Me]=8.88 eM; eeeee (Me/eeeeee) 8:8.8.

e βe=eeeeeeeeee eeeeeee eeee eeeee ee eeeeee.

e MMM=eeeeeeee eeeeeeeee.

e Meeeeeeeeeeee eee eee eeeee ee eeeee ee eee ee eee eeeeeeee.

Mee eeeeeee eeeeeeeeeeee eeeeeeeee eee eeeee eeeeeeeee ee eee eeee ee eeee eee eee eeeeeeee eeeeeeee. Mee eeeeeeee eeeeeeeeeee ee eeeeee eeeeeeee ee eee eeeeeee eeeeeeeeeee eeee eee-8-eee, e.e. ee eeeee eeee eeeeeee eee eeeeeeeeee eeeeeeeee eee-8-eee eeeeee. Meee, eee eeeeeee eeeeeeeeeee eee Meeeeeee ee eeeeee eeeee eeeee eeeeeeeeee eeee eeee eee MMMMM eeeeeeee eee eeeeee/eeeeeeee eeeee eee eee eeeeee ee eeeeee.

Meeeeeeeeeeeeeee ee eeeeee ee eeeeeeeeee eee e eeee eeeeeee ee eeee- eee eeeeeeeeeee eee ee eeeeee. Me ee eeeeeee, eee eeeeeeeeeeeeeeee ee eeee-8,8-eeeee ee eeee eeeeeeee (88) ee eeeeeeeee (Meeeee 8), eeeee eee eeee eeeeeeeee eeeeee eeee eee eeeeeee ee eeee eeee 88% eeeee,[‌88‌] eeee eee eeeeeeeee ee eee eeeeeeeeeee-eeeee eeeeeeee.[‌88‌,‌88‌]

Meeeee 8 Meeeeeeeeeeeeeee ee Meee-8,8-eeeee[‌88‌]

Meeeeeeeeee 8

Meeeee Meeee (M/Me) Meee (°M) Meeeeeee (eee) Meeee (M8/MM) MMMe (eee·eee8·e8) Meeeeeeeeeee,e (%) eee Meeeeeeee M8 Meeeeeee Meeeeeeeee,e (%) ee M8 Meeeeeee Mee
eeee 8:8 88 88 8:8 88 >88 88 [‌88‌]
eeee 8:8 88 88 8:8 88 88 e.e. [‌88‌]
eeee 8:8 88 88 8:8 88 <88 88 [‌88‌]
eeee 88 88 8:8 <8 [‌88‌]
Me8M 88:8 888 88 8:8 <8 [‌88‌]
88 88:8 888 88 8:8 888 88 88 [‌88‌]
eeee 88:8 888 88 8:8 888 <88 88 [‌88‌]
Meee 88:8 888 88 8:8 888 88 88 [‌88‌]
88 8:8 888 88 8:8 888 >88 88 [‌88‌]
eeee 88:8 888 88 8:8 888 88 88 [‌88‌]
eeee 8:8 888 88 8:8 888 >88e 88 [‌88‌]
eeee + Me8M (8 + 8):8 888 88 8:8 888 <88 e.e. [‌88‌]
eeee 88:8 888 88 8:8 <8 [‌88‌]
eeeeeee 8:8 888 88 8:8 <88 [‌88‌]
88 8:8 88 88 8:8 888 88 88 [‌88‌]
eeee 88:8 888 88 8:8 <88 [‌88‌]

e MMM=eeeeeeee eeeeeeeee.

e Meeeeee eeeeeeeee eeeeeeeee eeeeeeeeeeeee eee 8M.

e Mee eeeeeeeeeeeee eee eeeee eeee eeeeeeeeee eeeeeee eeee eeeeeee ee eeeeeeeee eeeeeeeee.

e e.e.=eee eeeeeeeeee.

e Mee eeeeeeeee ee eeeeee eeeeeeeee M8 eeeeeeee.

Meeeee 8 eeeee eeee eeee eeeeeeeee eeeeeeeeee eeeeeeeeee e M8 eeeeee eeee e eeee eeeeeeeeeee ee eeeeeeeeeeeeeeeeeeee eee eeeeeeeeee eeeeeeeeeeeee ee eee eeeee eeeeee eeee. Mee eeeeeeeee eeeeeeee eee eeeeeeeee ee eeeeeee eeeeeeeeeeeee, eeeee eee eee eeeeeee eeeeee, eee eee eeeee eeeee eee eee eeeeeeeee ee eee eeeee eeeeeeeeeeeee. Me ee eeeeeeee eeee eeeeeeeeeeeee eeeee eeeee eeeee eeeeeeeeeeeeeeee ee eee eeeee eeeeee eeee ee eee eeeeeeee eeeeee eeee ee eee eeeeeeeee eeeeeeeeeeee. Mee eeeeee eeeee ee eeee eeeeeeeeeeee ee eeeeeeeee ee Meeeeee ee eeee eeeeeeee ee eeeeee 88% eeeeeeeeeee.

8-(Meeeeeeeeeee)-8,8-eeeeeeeeeeeeee eee ee eeeeeeeee eeeee ee eeeeeeeeeeeeeeeee eeeeee eeeeeeeee eeeeeee eeee 8,8-eeeeeeeeeeeeeee, eee eee eeeeeeeee eeeeeeee eee eeeeeeeeeeee eeeeeeeee eeeeee. Meeeeeee, Meeeeeeee, eee ee-eeeeeee eeee eeeeeeeee e eeeee eeeee ee eeeeeee-eeeeeeeee eeeeeeeeeeeeeeee ee 8,8-eeeeeeeeeeeee, eeee ee eeeee eee eeeeeeeeeeee eeeeeeeee.[‌88‌] Meeeeeeeeeeeeeee ee 8,8-eeeeeeeeeeeeee eeeee eeeeeee eeeeeeeeee eeeee eeee eeeeee eee eeeeeee eeeeeeeee eee eeeeeeee eeeeeee ee Meeeee eee Meeeee.[‌88‌] Mee eeeeeeeee eeeeeeee eeeeeeee eeeeeeeeeee eee eeeeee eeeeeee. Meee eeeeee eee eeeeeeee eeeeeeeeeeee eeeeeee eee eeee ee eeee eeeeee eee eeee eee eeeeeee eee eeeeeeeee eeeeeeeee eeeeeeee ee eeee eee eeee eeeeeeeeeeee. Mee eeeeeeeee eeeeee ee eee eeeeeeeeeeee, e.e. eee eeeeeeeeeeeee eeeeeee, eee eee eeeeee ee eeee eee ee eeeeeeeeeee. Meeeeeee eee Meeeeeeee eeee eeeeeeeee e eeeeeeee ee eeee eeeeee eeeeeeeeee eee eeeeee eeee eee eeeeeeeeeee eeeeeeeee 88 eee ee eeeeeeeee eeee eeeeeee eeeeeeeee eeeeee (Meeeee 88). Mee eeeeeeee 88 eeeeee eeeee eeeeeeeeeee eee ee eeeeeeeeeeee ee eee eeeeeee eeeeeeeeeeeeeee eeeee eeeeeeee eee eeeeeeee(MM) eeeee ee eee eeeeeeee, ee eeeeeeeeeeeeeeeeee eeee eeeeee eeeeeeeeeee. M eeeeee eeeeeeee ee eee eeeeeeeeee ee eeee eeee; eeeeeeeeeeeee ee eee eeeeeee ee eee eeee eeeeeeeee eeee (eeee eeeee), eee ee eeee eeee eeee eeeeeee eeeeeeeeee ee eeeeeee eeeeeeeeeeeee eeee ee eeeeeeeeeeee eeeeeeeee.

Meeeee 88 8-(Meeeeeeeeeee)-8,8-eeeeeeeeeeeeee eeee 8,8-Meeeeeeeeeeee[‌88‌]

Meeeeee eeee eeeeeeeee ee eeeeeee eeeeeeeee eeee eeeeeeeeeeeeeeee eee eee eeeeee eeeeeeeee ee eeeee eee eeeeeeee eeeeee ee eeeeeeeee ee eeee eeee eeeee eeeeeeeeee eeeeee eeee ee eeeeee. Mee eeee eeeeeeee ee eeeeeeeeeeeeeeeeeeeee, eee eeeee e eeeeeee eeeeeee ee eeeeee eeeeeee eeee eeeee ee eeeeeeee eeeeeeee ee eeeeeeee eeee eeee-eeeeeeee eeeeeeeee. Mee eeee ee eeeeee-eeee eeeeeeeeeeeeeeeeeeeee eee eeeeeee eeeeeeeee ee Meeeeeeee eee ee-eeeeeee ee eee 8888e.[‌88‌] Meeeee eee ee-eeeeeee eeeeeeee e eeeeeeeee-eeeeeeee eeeeee eeeeeeee eeeeeeeeee ee eeeeeeeeeeeee ee ee eeeeeeee eeeeee ee eee eeeeeeee eeeeeeee, eeeeeeeeeeeeeeee ee eee eeeeee eeeeeeee, eee eeeeeeeee ee ee eeeeeee eeeeeeeeeeee, eeeee eeee eeeeeeeee eeeeeeeeeeeee.[‌88‌] Mee eeee eeeeeeee eee eeee ee eeee eee eeeeeeee eeeeeee. Meeeeee eeeeeeee eee eeeee ee Meeee 8.

Meeee 8 Meeeeeeeeeeeeeeeeeeee ee Meeeeee Meeeeee eee Meeeee[‌88‌]

Meeee Meeeeeeee Meeee Meeeeee Meeeeeeeeee (%) Meeeeeeeeee (%) eeeeee Meeeee Meeee (Meeeee/Meeeeeee) Meeee (%) ee Meeee Meeeeeee Mee
Meeeee Meeee
8 eeee-8-eee eeeeeeeeee 888 88 88:8 88 [‌88‌]
8 eeee-8-eee eeeeeeeeeeeee Me(MM8)8MMe8 888 88 88:8 88 [‌88‌]
8 eee-8-eee eeeeeeeeee 88 88 88:8 88 [‌88‌]
8 eeee-8-eee 8,8-eeeeeeeeeeeee 88 88 88:8 88 [‌88‌]
8 eeee-8-eee eeeeeeeeeeeeee 88 88 88:8 88 [‌88‌]
8 eeee-8-eee eeeee-8-eeeee 88 88 88:88 88 [‌88‌]

e Meeeeeeeee ee eeeeeeeee eeeee eeeee 88e.

Mee eeeeeeeeeeeeeeee eeeeeeee ee eee eeeee MeM(MM)8M eeeeeee, eeeee ee eeee eeee eee eeee eeee eeeeeeeeee ee ee eeee MM. Mee eeeeeeeee eeee ee eee eeeeeeee ee eee eeeeeeeeeeeee ee eee eeeeeee, eeeee eeee e eeeeeeee eeeeeee eeeeeee. Me ee eeeeeee eeee eee eeeeeeeeee ee eee eeeeeeeee eeeeeee {[Me(eee)8]MM8} ee eeeeeeeeee (eee eeee ee ee) ee eeeee eee eeeeeeeeeeeee ee eeee eeeee. M eeeeeeee eeeeeee eeeeeee ee eeee eee eeee eeeeeeee eee eeeeeeeeeeeee. Mee eeeeeeeeeee eeee (888°M) ee eeeeee eeee eeee eeee eee eeeeeeeeeeeeeeee (88888°M). M eeeeeee eeeeeeeeeeee ee eee eeeeeeeeee ee eeeeee ee eeeeeeee eee eeee eeeeeeee eeeeee eeeeeeee. Mee eeeeeeee eeeeeee eee eeeeeeeeeeee eeeeeeeee Meeeeeee eeee eeeee eeee eeeeee,[‌88‌] eee eeeeeeeeeeeee eeee eeeeeeeeeeee eeee eee eeeeeeeeeeeeeeee-eeeeeeeeeee Meeeeeee eeeeeeeeeee.[‌88‌,‌88‌] Mee eeeeeeee eeeee eeeeeeeeeeee eeee eeee eeeeeeeee eeeeee, eeeeeee, eeee eeeeeee eeeeee ee eeeee ee eee eeeee eeeee (Meeee 8, eeeee 8).

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

Meeeee 88 Meeeeeeee ee e 8-Meeee-8,8-eeeeeeeeeeeee-8-ee[‌88‌]

Meeeeeeeee eeeeeeeeeeeeeeee (MMM) ee ee eeee-eeeeeeeeee, eeeee eeeeeeee ee eeeeeee eeeeeee eeee eeeeeeeee eeeeeeeeeeeee. Meeeeeeee eee eeeeee eeeeeeeeeeeee ee eeee eee ee eeeeeeeee eeeeee eeee eeeee, eeeeee, eee eeeeeeee. Mee eeeeeeee, eee eeeeeeeeeeeeeeee ee eeeeeeee eeeee eeeeeeeee eee eeee ee eee eeeee eeeeee ee eeeeee eeeeeeeee, e eeeee ee eeee eeeeee eeee eeee-eeeeeeeeeeee eeeee eee eeeeeeeeeeee eeeeeeeeeee. Meeeeeee ee eeee 8-eeeeeeeeeeeee eeeee eee eeeeeeeee, eeeeeeee, eeeeeeeeee, eeeeeeeeee, eee eeeeeeeeeeee.

Mee eeeee eeeeee ee eeeeeeeeee eeeeeeeeeeeeeeee ee ee eeeeee e eeeee eeeeeeeeee ee eee eeeeeeee eeeeee, eee eeeeeeee e eeee eeeeeeeeeeee eeeeee ee eeeeeee. Me eeeee eeeeeeeee e eeeeeee eeeeeeeeee eeeeee eee eee eeeeeeeee ee eee eeeeeeee eeeeee eee ee eee eeeeeeeee eeeeeeeeeeeee ee eee eeeeeeee eeeeeeeeeeee; eeee eeeeeee eeee eeee >88% ee eee eeeeee eeeeeee. Meeeeee eeeeeeeee eeeeeeee eee eeeeeeeee eeeeeeeee eeee ee Meeeeeee eee eeee ee ee 88% ee eee eeeeee eeeeeee. Mee eeeeeeee ee eee eeeeeeee eee eeeeeee, ee eee eeeee eeeeeeeee eeeeeeeee eee eee eeeeeeeeee eee eeeeeeeee ee eee eeeeeee eeeee eeeee ee eeeeee eeee eeee ee eee eeeeeeee eeeeee.[‌88‌,‌88‌] Mee eee eeeeeeee eeee eeeeeeeee eeeeeeee eee ee e eeeeee, eeeeeeeee, eeeeeeeee eee eeeee eeeeeeeee eeeeeeeee eeee eeeeee eeeeeeeeeee eee eeeee eeeeee eeeeeeee eeeeeeeee.

Meeeeeee eeeeee eeeeeeeeee eeeeeee eeee eeee eeeeee ee eee eeeeeeeeee eeeeeeeeeeeeeeee ee eeeeeee eee eee eeeeeeeeeee. Meeee eeeeeeeeee eeeee eeeeeee eee eee-8-eeeeeeeeee (eeeee eeeeeee) eee eeeee eeeeeee. Mee eeeeee ee Meeeee eee Meeeee[‌88‌‌88‌] ee eeeeeeeeee eeee eeee e eeeeeeeeee eeeeee ee eeeeeeeeee eeeeeeee ee eeee eeee, eee eeee eeeeeeeeee e eeeeee ee eeeee eee eeeee eeeeeeeeee eee eeeeeee eeeeeeeeeeeeee (e.e., ee eee eeee eeeeeee). Me eeeeeeee, ee eeeee e eeeeee ee 88 eeeeeeee eeee-eeeeeeee eeeeeeee, 888 eeeeeee eee ee eeeeeeee ee eee eeee eeee. Meee e eeeeee (eeeee eeeeeeeeee ee eee eeeeeee) eee ee eeeeeeeeee eeee, ee eee eeee ee eeeeeeeeeeeeeeee, ee eee eeeeeee eeeee ee eee eeeeeeee ee eee eeeeeee eeeeeee eeeeeee, eeeee eeee eeeeeeeeeeee ee e eeeeee eeee eeeee eeee eee ee eee eeeeeeeeee eeee e eeee eeeeeeeeeeeeee ee eeee ee eeee. Me eee eeeeeee eeeee ee eee ee eee eeeeeeeeee eeee eee eeeeeee ee eeeeeee eeeeeee, ee ee eee eeee eee 8,8-eeeee eeeeeeeeeeeeeeee, eee eeee eeeeeeee eeeeeee eeeee eee eeeeeee e eeeeeeee eeeee eeee ee eee eeeeeeee eeeee eee eeee eeeeeeeee eeee eeeeeeee (ee eee eeee eeeeeeeeeeee, ee ee eee eeee eee eeeeee).[‌88‌] Me eee eeeeeeeee ee eee eeeeeee eeeee eeee eeeeeeeeee eeeeeeeeee, eee eeeeeeeee eeeeeee eee eeee eeeeee eee eeeeeeee eeeeeeeeeeee eeeee eeeee eeeee (eeeeeeeeee eeeee eeeeeeeeee ee eee eeeeeeeeeeeeee eeeeeeeee eee eeeeeeee eeee ee eeeeeeeeeeeeeeee). Meeeeeeeeee, eee eeeeee eee eeeeeeeee eee eeeeeeeeee eee eeeeeee eeeee ee e eeeeeee eeeeeee eeeeeee. Meeeee 88 eeeee e eee eeeeeeee.

Meeeee 88 Meeeeeeeeeee Meeeeeeee ee Meeeeeeee Meeeeeeeee[‌88‌]

Meeeeeeeeee 88

Meeeeee Meeee (88/88) ee (%) ee 88 Meeee (88/88) ee (%) ee 88 Meeee (88/88) ee (%) ee 88 Mee
Me-MMM 88:8 88 8.8:8 88 88:8 88 [‌88‌]
Me-MMM 88:8 88 8.8:8 88 888:8 88 [‌88‌]
MeeeMeee 88:8 88 8.8:8 88 88:8 88 [‌88‌]
Me-MMM 8.8:8 88 8.8:8 88 88:8 88 [‌88‌]

e Meeee (eeeee eeeeeeeee/Me) 8888:8 eee MeeeMeee, 8888:8 eee eee eeeee eeeeeee.

Mee eeeeeeeeee eeeeeee ee 8888%, eee eeeee ee eeeeeeeeee eeeee eee-8-eeeeeeeeee > eeeee eeeeeee > eeeeeee eee eee eeeeeee eeeeeeee ee eee eee eeeee ee Me-MMM.[‌88‌,‌88‌] Mee eeeeeee eee eeeeeeeee eeeee, eeeeeee eeee eee eeeeeeeeee eeee eeeeeeee. Meeee eeeee eeeeeeee ee eee eeeeeee eeee eeeee eeeeeeeeeeee ee eeeeeeeeeeeeeeeeee eeeeeee eeee eeeeeeee eee eeeeeeeeee eeeeeeeeeeeeeeee. Mee eeeeee eeeeeeee eeeee ee eeee eee eee eeeeeeee-eeee eeeeeeeeeeeeee eeeeeee, eeeee eeeeeeee eeee eeeeee eee eeeee ee 88°M. Mee eeeeeee, Me-MMM eeeee 88% eeeeeeeeee ee 8eeeee, ee e eeeeeeee eeeeeeeee ee >888e8. Meeeeee eee eeeeeee, MeMMM ee eee eeeee eeeeeeee-eeeeeeeee eee eee eeeeeee ee eee MMM eeeeeee, eee MM eeeeeeeeeeee ee eeeeeeeeee eeeeeeeee eeee eeee eeee eeee eeee eeeeee eee eeeee ee eeeeeeeeeeeeeee, e.e. eeee eee eeeeeeee eeeeee eeee eeeeeeee-eeeeeeeeeee eeeeeeeeee.[‌88‌] Meeeeee eeeeeeeeeee eeeee ee eeee eee eeeeeee ee eee eeee eee-eeeeee eeeeeee eeeeeeeee, ee ee, eee eeeeeee, eeee eeeee 8,8- eee 8,8-eee(eeeeeeeeeeeeeeeee)eeeeeee.[‌88‌] Meeeeeee, eee eeeeeee eeeeeeeeee ee ee eeeeeeeeeeeeeeee eeeeeee, eeeee eeeee ee eeeeee eeeeeeeee eeee eee-eeeeeeeeee eeeeeeeeeeee.

Meeeeeeeeeee Meeeeeeee

Meeeee Meeeeeeee 88; Meeeeee Meeeeeeee eee Meeeeeeeeeeeeeee ee Mee-8-eeee eeee Meeeeeeeeeeeeeeeee-Meeee Meeeeeeee:[‌88‌]

MMMMMMM: Meeeee eeeeeeee ee eeeeeeeee eeeeeeeee eee eeeee, eee eeeeeeee ee eeeeee eeeeeeeeeeeeee eee eeeeeee eeee ee e eeee.

MMMMMMM: Meeeeeeee eeeeeeeee ee e eeee eeeeeeee eee eeeeeeeeee, eeee eeeeeeeeeeee eeeeeeeeee eeeeeeeeee.

Mee eeeeeeeee eeee eeeeeeeee ee e 888-eM eeeeeeeee eeeee eeeeeeeee eeeeeeee eeee e eeeeeeee eeeeeee eee e eeeee eeeeee. Meeeeeee eee eeee ee ee eeeeeeee eeeeeeee eee eeeeeee (MMMMMMM: eeeeeeeeee) eee eeee ee eee eeeeeee ee eeeee ee eeeeeee eeeeeeeeeeeee ee eee eeeeeeee (e.e., ee eeeeeee). Mee eeeeeeeee eee eeeeeee eeee eee eeeeeeeee eeeeeee eeeeeee {[Me(MMe)(eee)]8}, eee eeeeee (Me8M), eee eeeeeeee eeeeeeee, eee eee eeeeeee. [Me(eeee)(MM)8 ee eee eeeeeeeee eeee eee eeee eeeeeee ee eeeeeee eeeeeee ee eeee eeeeeeee; ee eeee eeeeeeeeeeeeee eee eeeeeeeee ee eeeeeee eeeeeee eee eee ee eeeeeeee eeee eeeeeee eeeeeee ee eeee (eeeee ee eeeeeeeeeee eeeeeee eeeeeee eeeeeee eeeee eee eeeeeeeeee ee eeeeeee eeeeeee eee eeeeee eeee ee eeeeeeeee).] Mee eeeeeee eee eeeeeeeeeee (eeee MM/M8) eee eeeeeee ee eee eeeeeeee eeeeeeeeeee (88°M); eee eeeeeeeeeee eee eeeeeeeeee ee ee eeeeeeeeee eeeeeee eeeeee. Mee eeeeeeee eee eeee eeeeeeeee ee eeeeee eee eeeeeeeee eeeee e eeeeee eeeeeeeeeeee ee eeeeee. Meeeeee eeee eeeee ee eeeeeeeee eeee eee eeeeeee eee eee eeeeeeee eee eeeeeeee eeee M(MMe)8 ee eeeeeee eeeeeeeeeeeee ee eee eeeeee ee eee eeeeeee ee MM eeeeee eee eeeeeee eeee eeeeeeee ee MMM. Mee eeeeeee eeeeeeee eeeee (88% eeeeeeeeee) eeee eeeeeeeeee eeee eee eeeeeeee eeee eeeeeee eee eeeeeeeee eeee e eeeee-eeeee eeeeeeeeee ee eee eeeeee eeeeeeeeeeeee.

Meeeeeee (88); Meeeeee Meeeeeeee:[‌88‌]

MMMMMMM: Meeeee eeeeeeee ee eeeeeeeee eeeeeeeee eee eeeee, eee eeeeeeee ee eeeeee eeeeeeeeeeeeee eee eeeeeee eeee ee e eeee.

Mee eeeeeeeeee (888eM Meeeeeeee-M ee MM-888) eeee eeeeeee eeee eee eeee eeeeeeeee ee Meeeee 8 eeeee ee eeeeeeeeee ee M8 ee eeeee. Meee eeee eeeeee ee eee eeeeeeee eeeeeeeeeee eee eeee eeeeeeeeeee eeee MM/M8. Meeeee eee eeeeeeee eee eeeeeeee eee eeeeeee ee eeee ee 888eMe, eeeee eeeee eee eeeeeee eee eeeeeeeeeeeee. Meeee 8.88e (eeeeeeeee ee eee eeee), eee eeeeeeeeee eeee eeeeee eee eeeeeeeeeeeee, eee eee eeeeeeee eeee eeeeeeee.

8,8-Meeeeeeeeeeeeeee (88, Me8=Me8=Me):[‌88‌]

MMMMMMM: Meeeee eeeeeeee ee eeeeeeeee eeeeeeeee eee eeeee, eee eeeeeeee ee eeeeee eeeeeeeeeeeeee eee eeeeeee eeee ee e eeee.

M 888-eM eeeeeeeee eeeee eeeeeeee eeeeee eee eeeeeee eeeee M8 eeeee eeee 8,8-eeeeeeeeeeeeee (8.8eeee), MeM(MM)(MMe8)8 (8.888eeee), eee eeeee eeeeeee (88eM) (MMMMMMM: eeeeeeeeee). Mee eeeeeee eee eeee eeeeeeeeeee ee 888eee eeee eeeeee (MM/M8 8:8) eee eeeeee ee 88°M eee 88e. Meee eee eeeeeee eee eeeeeeee eee eeeeeeeee ee eeeee eeeeeeeeeeeeee (eeeeee eee, eeeeee/Me8M 8:8). Mee eeeeeeeeee eee 88% ee eeeee 88% eee 8,8-eeeeeeeeeeeeeeee. Meeee eeeee eeeeeeeeee eeee eeee 8% ee eee eeeeeeeeeeeee eeeeeee eee eeeeee, eee eeeee eeeeeeee eeeeeeeee eeeeeeeeee eee eeeeeeeeeeeee eeeee eeeeee ee ee eeee ee 88% ee eee eeeeeee eeeeeeee.

8-Meeeeeeeeeeeeee (Meeee 8, Meeee 8); Meeeeee Meeeeeeee:[‌88‌]

MMMMMMM: Meeeee eeeeeeee ee eeeeeeeee eeeeeeeee eee eeeee, eee eeeeeeee ee eeeeee eeeeeeeeeeeeee eee eeeeeee eeee ee e eeee.

Mee eeeeeeeeeeeeeeeeeeeee eeeeeeee eee eeeeeee eee ee e Meee eeeeeeeee eeeee eeeeeeeee (888eM). Mee eeeeeeeee eee eeeeee eeee e eeee ee [Me(eee)8]MM8 (8.8eee%), eeeeee (8.8eee%), eeee-8-eee (88.8eeee), eee eeeeeeeeee (88.8eeee) ee MeMM/eeeeeee (8:8; 88eM). Meeeeeeeeeee, eee eeeeeeeee eee eeeeeeeeeee eeee MM (8eee) eee M8 (88eee) eee eeeeee ee 888°M. Meeee 88e, eee eeeeeeeee eee eeeeeee ee eeee ee ee eee eee eeeee eeee eeeeee. Mee eeeeeee eee eeeee (MeMM8) eee eeeeeeee ee MM eeee eee(eeeeeeeeeeee) eeeee ee ee eeeeeeee eeeeeeee, eee ee MM/MM.

8-Meeeeeeeee-8,8-eeeeeeeeeeeee-8-ee (88); Meeeeee Meeeeeeee:[‌88‌]

MMMMMMM: Meeeee eeeeeeee ee eeeeeeeee eeeeeeeee eee eeeee, eee eeeeeeee ee eeeeee eeeeeeeeeeeeee eee eeeeeee eeee ee e eeee.

M eeeeeee ee 8,8-eeeeeeeeeeee-8-ee-8-ee (88; 888ee, 8.8eeee) (eeeeeeee eeee eeeeeeeeeeee eee eeeeeeeeeeeeee eeeeeee), eeeeeeeeee (8.8eM, 8.8eeee), eee [MeMe(eee)]8 (8ee, 88µeee) ee eeeee 8,8-eeeeeee (88eM) eee eeeeee ee 888°M eee 88e ee ee eeeeeeeee eeeee 88eee ee MM eee 88eee ee M8. Mee eeeeeeee eee eeee eeeeeeee eee ee eeeeeee eeeeeee e eeeee eee ee eeeee eeeeeee (eeeeeeee MMMMM) eee eee eeeeeee eee eeeeeee ee e eeeeee eeeeeeeeee. Mee eeeee eeeeeee eee eeeeeeeeeeee (MeMM); eeeee: 888ee (888%).

Meeeeeee eee Meeeee Meeeeeee Meeeeeeeeeeeeeee Meeeeeee 8888:[‌88‌]

MMMMMMM: Meeeee eeeeeeee ee eeeeeeeee eeeeeeeee eee eeeee, eee eeeeeeee ee eeeeee eeeeeeeeeeeeee eee eeeeeee eeee ee e eeee.

Meeeeeeeeeeeeeee eeeee eeee eeeeeeee ee eeeeeeee ee eeeeee eee Me(eeee)(MM)8 eeeee eeeee ee eeeeeee eeeeeeee ee eeeeeeee ee eeeeeee eee eeee eeeeee eeeeeeee. Mee eeeee eeeeee ee eeee ee eeee eeeeeee eeee eee 8.8eM. Meeee ee eee eeeeee (8.88M ee MMM) eee Me(eeee)(MM)8 (8.88M ee eeeeeee) eeee eeeeeeee ee e eeeeee ee ee. Mee eee-8-eeeeeeeeee eeee eee eeeeeeee ee eeeeee eee-8-eeeeeeeeee (88.88e, 8.88eee), eeeeee (8.88e, 8.888eee; ee e MM eeeeeeee eeeeeeee), eee eeeeeee (8.88e, 8.888eee). Mee eeeeeee eeee eee eeeeeeee ee eeeeee eeeeeee (88.88e, 8.888eee) eee eeeeeeee (8.88e, 8.888eee). Mee eeeee eeeeeee eeee eee eeeeeeee ee eeeeee eeeee eeeeeee (88.88e, 8.888eee) eee eeeeeeee (8.88e, 8.888eee). Mee eeeeeee/eee-8-eeeeeeeeee/eeeee eeeeeee/eeeeeeee eeee eee eeeeeeee ee eeeeee ee eeeeeee (88.88e, 8.888eee), eee-8-eeeeeeeeee (8.88e, 8.888eee), eeeee eeeeeee (8.88e, 8.888eee), eee eeeeeeee (8.88e, 8.888eee) (8:8:8:8.8eeeee eeeee).

Meeeeeeeeeeeeeee eeeeeeeee eeee eeeeeeeee ee ee Meeeeeee Meeeeeee eeeeeee eeeeee eeeeee ee ee eeeee-eeeeeeeeee eeeeeeee. Mee eeeeeee eeeeee eeeeeeeee ee eeeee eeeeeeee, eeeeeeeeeeee eeeeeee eeeeeeee eeeeeeee eeee eeeeeeeeee eeeeeeeeeee eee eeeeeeee eeeeeeee. Meee eeeeeeee eee eeeeeeee eeeee, eee eeeeeeee eeee eeeeeeeeeee eeee eee eeeeeee eeeeeeee ee eeeeee (M8/MM 8:8) eee eeee eeeeee ee 88°M eeeee eeeeeeee ee 888 eee. Mee eeee eeee eeeeeee eeeee 8e ee eeeeeee eee eeeeeee eee eeeeee. Meee eeeeeee eee eeeeeee, 88µM ee eeee eeeeeee eee eeeee eee eee eeeeeee eeee eeeeeee (8.8eM), eee eeee eeee eee eeeeeeee ee MM. Mee eeeeeeee ee eeeeeee eee eeeee eeeeeee eeeeeeee, Meeeeeeʼe Meee Mee 888 eeeeee eee eeee. Meeeee eeeee Me-MMM: 88% (eeeeeee eeeeeeee), 88% (eee-8-eeeeeeeeee eeeeeeee), eee 88% (eeeee eeeeeee eeeeeeee). Mee ee eeeeee eee eeeeeeee/eeeeee eeeeeee eeeeee eee Meeeee 88.