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Evano, G., Science of Synthesis, (2007) 20, 160.
As previously mentioned, carboxylation of organolithium reagents is another frequently used and useful approach toward the synthesis of carboxylic acids 61 from halogenated compounds 60. It also appears to be one of the most efficient methods. Organolithium reagents are generally formed by lithium–halogen exchange with the use of butyllithium or tert-butyllithium. After carboxylation of the lithiated intermediates, the carboxylic acids are usually obtained in good yields; representative results are collected in Table 13. The only drawback of this reaction is the high basicity and nucleophilicity of organolithium reagents, which can result in the formation of byproducts when acidic or electrophilic centers are present in the starting halide. Careful control of the temperature can, however, prevent most of these undesired side reactions. Moreover, the rapidity of the lithium–halogen exchange, even at temperatures close to the freezing points of diethyl ether or tetrahydrofuran, allows for the preparation of organolithiums containing other reactive functional groups (esters, epoxides, nitro groups). Lithium–halogen exchange proceeds faster with iodides than with bromides; chlorides are less reactive toward this exchange, fluorides are inactive, and with these substances deprotonation usually proceeds faster than lithium–halogen exchange. This allows selective metalation reactions with starting materials containing different halogen atoms. The exchange reaction is accelerated by the presence of ether solvents such as diethyl ether or tetrahydrofuran, with the best solvent system being ether/pentane mixtures, since they lead to relatively few byproducts. The use of N,N,N′,N′-tetramethylethylenediamine should be avoided, since it accelerates deprotonation more than the exchange reaction.[112]
Mee eeeeee ee eee eeeeeeeeeeeee eeeeeee eeee ee eee eeeeeeee eeeeeeee eeee eeee eeeeeee. Meeeeee–eeeeeee eeeeeeee ee ee eeeeeeeeeee eeeeeee eeeeeeee eee eeeeeeeee ee eee eeee eeeeee eeeeeeeeeeeee.[888] Meee eeeeee eee eeeeeeeee eeeeeee eeeeeeeeee ee ee eeeeee: (e) Meeeeeeeeeee eee ee eeee ee eeee ee eeeeeeeeeeeee eeee ee eeee eeeeee, eeeee eee eeeeeee eeeeeee, eeee ee, eee eeeeeeee eeeeeee eee eeeeeeeeeee eee eee eeeeeeeeee ee eeee; (e) Mee eeeeeeeee ee eeeeeeeee eeeeeeeeeeeee eeeeeeee ee eeeeeee–eeeeeee eeeeeeee ee eeeeee eeeeeeeee; eee (e) Mee eeeeeeeeeee eee ee eeeeeeeee ee eeeeeeeeeee ee eee eeeee eeeeee eeeeee. Meeeeeeee, eee eee ee 8 eeeeeeeeeee ee eeee-eeeeeeeeeeee eeeee eee eeeeeeeee ee e eeee eeeee ee eeeeeeeeeeeee eeeeeeee eeeeeeee, eeeee eee eeeeee eeeeeeeeee eeeeee eee eeeeeeee eeeeeee ee eeeeeeeeeee eee eeeeee eeee eeee-eeeee eeeeee, ee eeee eeeeeeeee eee eeeeeeeee.[888]
Meeee 88 Meeeeeeee ee Meeeeeeeee Meeee eeee Meeeeee ee Meeeeeeeeeeeee ee eee Meeee Meeeeee eeee Meeeeeeeeeeee Meeeeeee, Meeee Mee ee Meeeee Meeeeee[888–888]
Meeee | M8 | M | Meeeeeeeee | Meeee (%) | Mee | Meee 8 | Meee 8 |
---|---|---|---|---|---|---|
8 | (MM8)8MM=MM8 | M | e-MeMe, eeeeeee, Me8M, −88°M, 8 eee | MM8(e), −88°M, 88 eee, eeee −88°M ee ee | 88 | [888] |
8 | Me | e-MeMe, eeeeee, MMM, −88°M, 8 e | eee eee, −88°M | 88 | [888] | |
8 | M | e-MeMe, eeeeeee, Me8M, −88°M | eee eee, −88°M | >88 | [888] | |
8 | Me | e-MeMe, eeeeeee, MMM, −88°M | eee eee, −88°M ee ee, 8 e | 88 | [888] | |
8 | Me | e-MeMe, MMMMM, eeeeeee, −88°M, 88 eee | eee eee, −88°M, 8 e | 88e | [888] | |
8 | Me | MeMe, eeeeee, MMM, −88°M, 88 eee | MM8(e), −88°M, 88 eee eeee −88°M ee ee | 88 | [888] | |
8 | M | MeMe, eeeeee, MMM, −88°M, 88 eee | eee eee, ee | 88 | [888] | |
8 | Me | MeMe, eeeeee, MMM, −888°M, 8 eee | MM8(e), −888°M, 88 eee | 88 | [888] | |
8 | M | e-MeMe, eeeeeee, Me8M, −88°M, 88 eee | eee eee, ee | 88 | [888] | |
88 | Me | MeMe, eeeeee, MMM, −88°M, 88 eee | eee eee, ee, 88 eee | 88 | [888] | |
88 | Me | e-MeMe, eeeeee, MMM, −88°M, 8 eee | eee eee, −88°M ee ee | 88 | [888] |
e M eeeeeee eeeeeee eeeee.
Meee eeee-eeeeee eeeeeeeeee eeeeee ee eeee ee eeeeeeeeee eeeeee ee eee eeeeeeee eeeeeeee, eeee eeeeeeeee ee eeeeeeeeee eeeeeeee eee eee eeeeeeeee ee e eeeeeeeeee eeee eeee e eeeeee ee eeeeeee eeeeeeeeee. Meeeeeee eee eee eeeeeeeee ee eeeeeee eeeeeeeeeeeeeee eeeee 88 eee 88, eeee eee eeeeeeeeeeeee eeeeeee 88 eee 88, ee eeeee ee eee eeeeeeeee ee (+)-eeeeeeeeeee M[888] eee eeeeeeeeeeeeeeeee,[888] eeeeeeeeeeee (Meeeee 88).
Meeeee 88 Mee Meeeeeeeeee ee Meeee Meeeeeeee ee Meeeeee Meeeeeeeee Meeee eeee Meee Meeeeee eee Meeeeeeeeeeee Meeeeeee[888,888]
Meeee eeeeeeee eeee eeee eeeeeeeee eee eeeeeeeee eeeeeeeeee, eeeeeeee eee eeeeee eeeeeeeeee ee eee eeeeeeeee ee eee eeeeeeeeeeee eeeeeeeeeeeee eeeeeeee. Mee eeeeeeee ee eeeee eeeeeee 88 eeee eeeeeee eeeeeee eeeeee eeee ee eeeeeee eeeeeeeeeeeee ee eeeeeee ee-eeee-eeeeeeeeeeeeeeee (MeMMM) ee eeeeeeeeeeeeeee ee −88°M eeeee ee e eeeeeeeeeeee eeee eeeeee ee eeeeeeeee ee eeeeeeeeeeeee eeeeeeee[888] (Meeee 88) ee eeee eeeeeeeeee eeeee 88 ee eeee eeeeee eeeee eeeeeee eeeeeeee eeee eeeeee eeeeeee. Mee eeeeeee ee eeee eeeeeeeee, eee eeee eeeeee eee eeeeeeeee ee eeeeeeeeeeeee eeeeeeee eeee eeeeeeeeeee eeeeeeeee (e.e., Meeee 88, eeeee 8).
Meeee 88 Meeeeeeee ee Meeeeeeeee Meeee eeee Meeeeee ee Meeeeeeeeeeeee ee Meeeeeeeeeeee Meeeeee eeee Meeeeee Meeeeee Meeeee, Meeeeeee ee Meeeee Meeeeee Meeeeeee[888–888]
Meeee | M8 | M | Meeeeeeeeee | Meeee (%) | Mee | Meee 8 | Meee 8 |
---|---|---|---|---|---|---|
8 | Me | MeMMM, MMM, −88°M | eee eee | 88 | [888] | |
8 | M | MeMMM, MMM, −88°M, 8 e | eee eee, −88°M ee ee | 88 | [888] | |
8 | Me | 8. MeMe (8.8 eeeee), MMM, −88°M 8. eeeeeee eeeeeeeeeeeee, −88°M |
MM8(e), −88°M, 8 e, eeee ee | 88 | [888] | |
8 | Me | 8. MeMe (8.8 eeeee), MMM, −88°M 8. MeMMM, −88°M, 8 e |
MM8(e), −88°M, 88 eee, eeee ee | 88 | [888] | |
8 | (MM8)8Me | M | MeMMM, MMM, 8°M | MM8(e), −88°M ee 8°M | 88 | [888] |
e MeMMM = eeeeeee ee-eeee-eeeeeeeeeeeeeeee.
Meeeeeeeeeee Meeeeeeeee
Meee-8-eeeee Meee [88, M8 = (MM8)8MM=MM8]; Meeeeee Meeeeeeee:[888]
MMMMMMM: M 8 M eeeeeeee ee eeee-eeeeeeeeeeee ee eeeeeee eeeeeee ee eeeee eee eee eeeeee eeeeeeeeeee eeee eeeee.
M eeee ee 8-eeeeeee-8-eee [88, M8 = (MM8)8MM=MM8; M = M; 888 ee, 8.8 eeee] ee e eeeeeee ee eeeee eeeeeee (88 eM) eee eeeee Me8M (8 eM) eee eeeeee ee −88°M, eee eeee eeeeeee eeeeeeee eeee e 8.88 M eeee ee e-MeMe ee eeeeeee (8.88 eM, 8.88 eeee); eee eeeeeee eee eeeeeee eee ee eeeeeeeeee 8 eee ee −88°M. Mee MM8 eee eeeeeee eeeeeee eee eeee ee −88°M eee ee. 88 eee. Mee eeeeeee eeee eee eeeeeee, eee eeeeeee eee eeeeeee ee eeee ee 88°M, eee 88% ee MMe (88 eM) eee eeeee. Mee eeeeeee eeeee eee eeeeeeeee, eee eeeeeee eeeee eee eeeeeeeee eeee Me8M (8 × 88 eM), eee eee eeeeeeee eeeeeee eeeeee eeee eeeeeeeee eeee eee. ee MeMMM8 (8 × 88 eM). Mee eeeeeee eeeee eeee eee eeeeeeeee eeee eeeee ee MMe ee eM 8 eee eeeeeeeee eeee Me8M (8 × 88 eM). Mee eeeeeeee Me8M eeeeeeee eeee eeeee (MeMM8), eeeeeeee, eee eeeeeeeeeeee; eeeee: 888 ee (88%).
8-(8-Meeeeeeee-8-eeee)-8-[8-(eeeeeeeeeeeeee)eeeeeeeeeeeee]eeeeeee Meee {88, M8 = 8-(8-Meeeeeeee-8-eeee)-8-[8-(eeeeeeeeeeeeee)eeeeeeeeeeeee]eeeeee}; Meeeeee Meeeeeeee:[888]
M 8.88 M eeee ee MeMe ee eeeeeee (888 μM, 8.88 eeee) eee eeeee eeeeeeee ee e eeeeeeee eeee ee 8-eeeee-8-(8-eeeeeeeee-8-eeee)-8-[8-(eeeeeeeeeeeeee)eeeeeeeeeeeee]eeeeeee {88, M8 = 8-(8-eeeeeeeee-8-eeee)-8-[8-(eeeeeeeeeeeeee)eeeeeeeeeeeee]eeeeee; M = Me; 888 ee, 8.88 eeee} ee eeeeeee eeeeeeeee eee MMM (88 eM) eeeeee ee −888°M (Me8M/eee M8 eeee). Mee eeeeeeeee eeee eeeeee eeee eee eeeeeee ee −888° M eee 8 eee eeeeee MM8 eee eee eeeeeee eeeeeee ee eee 88 eee. M eee. MM8Me eeee (88 eM) eee eeee eeeeeeeee eeeee eeeeeeee ee eee eeeeeeeee eeeeeee. Mee eeee eee eeee eeeeeeeee eeee Me8M (8 × 88 eM). Mee eeeeeeee eeeeeee eeeeee eeee eeeee eeee eeeee Me8MM8 (88 e), eeeeeeee, eee eeeeeeeeeeee. Mee eeeeeee eee eeeeeee eeeeeeee ee eeeeee eeeeeeeeeeeeee (eeeeee eee, MeMMe/eeeeeee 8:8); eeeee: 888 ee (88%).
8-Meeeeeeeeeee[8.8.8]eeeeeee-8-eeeeeeeeee Meee (88, M8 = 8-Meeeeeeeeeee[8.8.8]eeee-8-ee):[888]
M eeee ee 8-eeeee-8-eeeeeeeeeee[8.8.8]eeeeeee (88, M8 = 8-eeeeeeeeeeee[8.8.8]eeee-8-ee; M = M; 8.8 e, 8 eeee) ee MMM (88 eM) eee eeeee eeeeeeee ee e 8.8 M eeee ee eeeeeee ee-eeee-eeeeeeeeeeeeeeee ee MMM (88 eM, 88 eeee) eeeeee ee −88°M. Meeee eee eeee eeee eeeeeee eee eeeeeee eee 8 e ee eeee eeeeeeeeeee, e eeeeeee eeeeee ee eeeeeeee eee eee eee eeeee ee e eeeeee eeeeeee. Mee eeeeeee eee eeeeeee ee eeee ee ee eee eee eeee eeeeeeeee eeee 8% MeMMM8 eeee (8 × 88 eM). Mee eeeeeeee eeeeeee eeeeee eeee eeeeeeeee ee eM 8–8 eeee eeeee MMe ee 8°M, eeeeeeeee eeee MeMe, eee eeeeeeeee eeee Me8M (8 × 88 eM). Mee eeeeeeee eeeeeee eeeeee eeee eeeee (MeMM8), eeeeeeee, eee eeeeeeeeeeee. Mee eeeeeee eee eeeeeee eeeeeeee ee eeeeee eeeeeeeeeeeeee (eeeeee eee, Me8M/eeeeeee 8:8); eeeee: 888 ee (88%).
References
[112] | Meeeeee, M., Me Meeeeeeeeeeeee: Meeeeeeeeee eee Meeeeeeee, Meeeeee, M. M.; Meeeeeee, M. M., Mee.; Meeeeeee: Meeeee, (8888); e 888. |
[113] | Meeeee, M.; Meeee, M. M., M. Me. Meee. Mee., (8888) 88, 8888. |
[114] | Meeee, M. M.; Meeeee, M. M., M. Me. Meee. Mee., (8888) 88, 8888. |
[115] | Meeeee, M. M.; Meee, M. M.; Meeeeeee, M. M.; Meee, M., M. Me. Meee. Mee., (8888) 888, 8888. |
[116] | Meeeee-Meeeeee, M. M.; Meeeee, M. M.; Meeeee, M. M., Meeeeeeeeee, (8888) 88, 88888. |
[117] | Meeeeeee, M.; Meeeeeee, M.; Meeeeee, M. M.; Meee, M. M., M. Mee. Meee., (8888) 88, 8888. |
[118] | Meeeeeee, M. M.; Mee, M., M. Me. Meee. Mee., (8888) 888, 88888. |
[119] | Meeeeeee, M.; Meeeeeeee, M. M., M. Mee. Meee., (8888) 88, 8888. |
[120] | Meeeeeee, M. M.; Meeee, M. M.; Meeeeeee, M. M.; Meee, M.; MeMeeeee, M. M.; Meeeee, M.; Meee, M. M.; Meeeeeeee, M.; Me, M. M.; Meeee, M. M., M. Mee. Meee., (8888) 88, 8888. |
[121] | Meeee, M.; Meeeeeeee, M., Mee. M. Mee. Meee., (8888), 888. |
[122] | Meeeeeeee, M.; Meeee, M.; Meeeeee, M.; Meeeeeeee, M.; Meeeíeee, M.; Meeee, M. M., M. Me. Meee. Mee., (8888) 888, 8888. |
[123] | Meeee, M.; Meee, M.; Meeeeeeee, M., Mee. M. Mee. Meee., (8888), 8888. |
[124] | Meeó, M.; Meeeeeeeeeeee, M., M. Mee. Meee., (8888) 88, 8888. |
[125] | Mee, M.; Meeeeee, M. M., Meeeeeeeeee Meee., (8888) 88, 8888. |
[126] | Meee, M.; Mee, M.; Meeeee, M.; Meee, M.; Meeee, M., Mee. Meee., (8888) 8, 888. |
[127] | Mee, M.; Mee, M. M.; Mee, M.; Meeee, M.; Meeeeeeeeee, M. M., Meeee. Meee., (8888) 888, 8888; Meeee. Meee. Mee. Me., (8888) 88, 8888. |
[128] | Meeeeee, M. M.; Meeeeeeeee, M. M., M. Mee. Meee., (8888) 88, 8888. |
[129] | Meeeee, M. M.; Meee, M. M.; Meeeeee, M.; Mee, M.; Meeeee, M. M., Meeeeeeeeee Meee., (8888) 88, 8888. |
[130] | Meeeeee, M.; Meeeeeeeee, M. M.; ee Meeeeee, M., Mee. M. Mee. Meee., (8888), 8888. |
[131] | Meeäeee, M.; Meeee, M., M. Mee. Meee., (8888) 88, 88. |
[132] | Meeeeee, M.; Mee, M., Meeeeeeeeee: Meeeeeeee, (8888) 8, 8888. |
[133] | Mee, M., Meeeeee, M. M.; Meeeeeee, M., Meeeeeeeeee Meee., (8888) 88, 8888. |
Meeeeee Meeeeeeeeee
- 8.Meeeee-Meee, (8888) M 8-8, 888.
- 8.Meeeee-Meee, (8888) M 8-8, 888.