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Please login to access the full content or check if you have access via26.4.1.1.1.5 Variation 5: Nucleophilic Acylation of Carboxylic Acid Derivatives by Acyllithium Reagents
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Landais, Y.; Vincent, J. M., Science of Synthesis, (2005) 26, 660.
The insertion reaction of carbon monoxide into a C—Li bond generates an acyllithium intermediate that can then react with electrophiles to give the corresponding carbonyl derivatives.[43] This strategy has been used to prepare various symmetrical and unsymmetrical alkyl- and/or aryl-substituted 1,2-diketones in an efficient manner.[44,45] As described in Section 26.4.1.1.1, this method is of general use and leads to functionalized unsymmetrical 1,2-diketones in good yield, which can be extended to reactions on a large preparative scale. For the method to be of synthetic value, the acyllithium intermediate must be generated at very low temperatures (−135 to −110°C). At such low temperatures, the reaction of organolithiums with carbon monoxide is generally much faster than the direct alkylation of the electrophile. Moreover, the reaction of the acyllithium is also faster than any other processes that might consume the acyllithium intermediate. Therefore, these reactions are generally carried out by mixing the organolithium and carbon monoxide in the presence of electrophilic substrates in the same vessel at very low temperatures. In the first protocol used for this reaction, carbon monoxide is bubbled through a solution of 2 equivalents of the ester (electrophile) in tetrahydrofuran/diethyl ether/pentane (4:4:1) and then 1 equivalent of organolithium reagent is added very slowly at −110°C. However in some cases byproducts resulting from the direct addition of the organolithium or the acyllithium to the electrophile appear in various amounts. Thus, a second protocol has been introduced that involves using a stoichiometric amount of the organolithium and the ester at −110°C in tetrahydrofuran/diethyl ether/pentane (4:4:1) (Scheme 17).[44] Still better yields of the 1,2-diketone 62 are obtained at −135°C by using the same organolithium/ester ratio but in dimethyl ether/tetrahydrofuran (3:1), which maintains the fluidity of the medium. The reactions have been carried out on a 10 millimole scale but have also been performed on a preparative scale thus providing 1,2-diketones 62 in good yield.
Meeeee 88 Meeeeeeeeeee Meeeeeeee ee Meeeee ee Meeeeeeeeee Meeeeeee[88]
M8 | M8 | Meeee (%) | Mee |
---|---|---|---|
Me | Me | 88 | [88] |
Me | 8-eeeee | 88 | [88] |
Me | eMe | 88 | [88] |
e-Me | Me | 88 | [88] |
e-Me | Me | 88 | [88] |
Mee eeeeeee eee eeee eeeeeee ee eeeeeeee, eeee ee eeeeeee eeeeeeeee, eeeeee eeeeeeeeeeeeee 8,8-eeeeeeee 88 ee eeee eeeee (Meeeee 88).[88] Meee eeeeeee ee eeeeeeee eeeeeee, eee eeeeeeee eeeeeee eee eeeeeee 8,8-eeeeeeee 88 ee e eeeeee eeeeee, eeeee ee eeeeeeee ee eee eee eeeeeeee eeeee eee eeeeeeeeeeeee eeeeeee 88. Meeeeee, eeeeeeeeee eee eeeeee eee eeee ee eeee ee eeee eeeeeee eee eeee eeeeeeee eeeeee ee 8,8-eeeeeeeee, eeee ee eeeeee eee eee eeeeeeeeeeeee ee eeeeee eee eee eeeeeeeee ee 8,8-eeeeeeeee eeeee eeee eeeeeeeeeee.
Meeeee 88 Meeeeeeeeeee Meeeeeeee ee Meeeeeee ee Meeeeeeeeee Meeeeeee[88]
Meeee eeeeeeeeeeee eeeeeeeee ee ee eeeeeeeeeee ee e eeeeeeeeeeeeeee eee eeeeee eeeeee eee eee eeeeeeeeeee ee 8,8-eeeeeeeee, eeeeeeeeeeee eeeeeeeeee ee ee eeeeeee eeeeeeeee eeeee eee eeee eeeeee ee eee eeeeeee eeeeeeee eee eeeeeeee eeee eeee eeeeeeeeee eeeeeeee 8,8-eeeeeeeeeeeeeeeeeeeee.[88,88] Mee eeeeeeeeeeee eeeeeeeee eeeeeeee ee eeeeeee ee eeeeeee eeeeeee eee eeeeeeeeeeee eeeeeeee ee ee eeeeeeeeeee eeee ee 88 ee eee eeeee, eeeee eeeeeeee eee eeeeeee eeeeeeee eeeeeeeeeeee 88, ee eeeeeeeee ee eee eeeeeeee ee eeeeeeeeeeeeeeeeeeeee eeee eeeeeee eee eeeeeeeeeeeee eeeeeeeee eeeee 88 (M8 = e-Me; M8 = Me; M8 = Me) ee 88% eeeee (Meeeee 88). Meeeeeeeeee ee eeeeeee eeeeeeee eeee 88 eeeeee ee e eeeeee eeeeeeeeeee ee eeee eee eeeeeee 8,8-eeeeeeee 88. Mee eeee eeeeeeee eeee eeeeeeee eee eee eeeeeeee ee eee eeeeeeeeeeeee eeee eeeeee eeeeeeee ee eeeeeeee 88 ee eeeeeeeeeeee ee eeeeeeee e eeeeee-eeeeeeee eeeeeeee, eeeee eee eeee eeeee eeee ee eeee eee eeeeeeeeeeee.[88–88] Meee eeeeeeeeeeee (M8 = eeee), eeee eeeeee-eeeeeeee-eeeeeeee eeeeeee ee eeeeeee ee ee eeeeee eeee eeee eeeeeeeee ee eeeeeeeeeeee. Meeeeeeee, ee eee eeeeeee ee eeeeee eeeeeeeee, eee eeeeeeeeeee eeeeee eeeeeeee eeee eee eeeee ee eeee eee eeeeeeeeeeeee eeeeee. Me eeeeeeeeeee eeeeeeeeeee ee eeeee ee eee eeeeeeeeee ee ee eeeeeeeeeee eeeeeee eee eeeeeeeeeee 88 eee eee eeeeeeeeeeeee (Meeeee 88). Me eeeeee eeeeeeeee eeeeeeeee, eeeeeeee ee eee eeee eeeeeeee eeeeeeeeeee 88 (ee eeeeeeee ee eee eeeeeeeeeeeee) eeee eee eeeee ee eeeeeee, eeeeeee ee eee eeeeeeeee ee eee eeeeeee 8,8-eeeeeeee 88. Meeeeeeeeeeeeeee eee eeee eeee ee eeee eeeeeee eee eeeeee eeeeeeeee ee eeeeeeeeeeee 88. Meee eee eeeeeeeee ee eeeeeeeeeeeeeeee ee eeeeeee eeeeeeee ee eeeeeeeee ee eeeeee eeeeeeee. 8,8-Meeeeeeee eee eeee eeeeeeee, eeeeee ee eeeeeeee eeeee, ee eeeeeeeeee eeeeeeeee ee eee eeeeeeeeeeeeeee eeee ee eeee eeeeeeee ee eee eeeeeeee ee e eeeeeeeee eeeeeeee.[88]
Meeeee 88 Meeeeeeee ee eee Meeeeeeeeeee Meeeeeeee ee Meeeee ee Meeeeeeeeee Meeeeeee[88,88]
Meeeeeeeeeee Meeeeeeee
8-Meeeeeeeeeee-8,8-eeeee (88, M8 = Me; M8 = eMe); Meeeeee Meeeeeeee:[88]
MMMMMMM: Meeeee eeeeeeee ee eeeeeeeee eeeeeeeee eee eeeeeeee ee eeeeee eeeeeeeeeeeeee eee eeeeeee eeee ee e eeee.
M 8-M eeeee-eeeeee, eeeee-eeeeeeee eeeee eeeeeeee eeee e eeeeeeeeee eeeeeee, e Meeeeee eeeeeee (eeee eee eeeeee eeee e eee-eeeeeeeeeee eeeeeeeeeee eee e eee eeeeee eeee), eee e ee-eee eeeeeee eeeee eeee e eee eeeeeeeeee eeee (eeeee eee eeeeeeeee ee e MM eeeeeeee) eee eeeeeee eeee eee M8 eee eeeeeee eeee MMM (888 eM), Me8M (888 eM), eeeeeee (888 eM), eee eeeeee 8-eeeeeeeeeeeeeeee (8.88 e, 88 eeee). Meee eeee eee eeeeee ee −888°M eee eeeeeee MM eee eeeeeee eeeeeee eee eeee eee ee. 88 eee. Meeee eee eeee ee MM, 8.88 M MeMe ee eeeeee (88.8 eM, 88.8 eeee) eee eeeee, eeee eeeeeeee, ee e eeeeeeeeee eeee ee eeeee 8.8 eeee·eee−8 eeeee e eeeeeee eeee. Meee eee eeeeeeee eee eeeeeeee, eee eeeeee ee eeeeee-eee eeeeeee eee eeeeeee ee −888°M eee 8 e (eeeeee ee MM eee eeeeeeeeee). Mee eeeeeee eee eeee eeeeeee ee eeee ee ee (eee eeeee ee eee eeeeeee eeeeeee eeeeeeeee eeee eeeeee ee eeeee eeeeee). Mee eeeeeee eee eeeeeeeeee eeee eeee eee. ee MM8Me (888 eM) eee eee eeeeee eeee eeeeeeeee, eee eeeeeee eeeee eee eeeeee eeee Me8M (8 ×), eee eee eeeeeee eeeeee eeee eeeeeeee ee eeee e eeeeee eeeeeee eeee. Meee eee eeeee (MeMM8), eeeeeeee, eee eeeeeeeee ee eeeeeee eeeeeeee ee eeeeee eee eeeeeeee. Mee eeeeeee eee eeeeeeeeeeee eeeeeeeee (8-ee eeeeee-eeeeeeee Meeeeee eeeeee) (ee 88–88°M/88 Meee) ee eeee eee eeeeeee; eeeee: 8.88 e (88%); 88% eeee ee MM.
References
[43] | Meeeeeee, M.; Meeeeeeee, M. M.; Mee, M. M.; Meee, M.-M.; Meeeee, M. M., M. Mee. Meee., (8888) 88, 8888. |
[44] | Meeeeeee, M.; Meeeeeeee, M. M.; Mee, M. M.; Meee, M.-M.; Meeeee, M. M., M. Mee. Meee., (8888) 88, 8888. |
[45] | Meeeeeee, M.; Mee, M. M.; Meee, M.-M., M. Mee. Meee., (8888) 88, 8888. |
[46] | Meeeeeee, M. M.; Meeeeeee, M., M. Mee. Meee., (8888) 88, 8888. |
[47] | Meeeeeee, M. M.; Meeeeeeeeee, M.; Meeeee, M., Meeeeeeeeee Meee., (8888) 88, 8888. |
[48] | Meeeeee, M. M.; Meeeeee, M. M.; Meeee, M. M.; Meeeeeee, M. M.; Meeeeeeeee, M. M., M. Me. Meee. Mee., (8888) 88, 8888. |
[49] | Meeeeee, M.; Meeeeee, M.; Meeeeee, M., Meeeeeeeeee Meee., (8888) 88, 8888. |
Meeeeee Meeeeeeeeee
- 8.Meeeee-Meee, (8888) M 8-8, 8888.