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Gribble, G. W., Science of Synthesis, (2006) 8, 387.
Like pyrrole (see Section 8.1.14.5.1), N-substituted indoles are preferentially deprotonated at C2, a position acidified by the inductive electron-withdrawing ability of nitrogen. Following studies on the lithiation of 1-methylindole with butyllithium (Et2O, reflux, 8 h) and carboxylation to give 1-methylindole-2-carboxylic acid (78%),[323] Sundberg explored the use of N-protecting/activating groups that permit C2 lithiation under milder conditions and whereby the N-protecting group can be removed (unlike N-methyl).[324] Snieckus has summarized the use of indole N-protecting groups in C2 lithiation,[236] and a selected list of indole C2 lithiation reactions (e.g., to give 75) is shown in Table 5. This list is not complete, but depicts only a few examples with each N-protecting group. Depending on the end use, all of these N-protecting groups have utility in synthesis; with the exception of N-methyl, all of the protecting groups are usually easily removed.
Meeee 8 M8 Meeeeeeeee Meeeeeeee ee Meeeee[888,888–888]
M8 | Meeeeeeeee | M+ | M | Meeee (%) | Mee |
---|---|---|---|---|---|
Me | MeMe, Me8M, eeeeee, 8 e | MM8 | MM8M | 88 | [888] |
Me | MeMe, Me8M/eeeeee, eeeeee, 8 e | (MM8Me)8 | MMMM8M | 88e | [888] |
Me | MeMe, Me8M/eeeeee, eeeeee, 8 e | M8 | M | 88 | [888] |
Me | MeMe, Me8M/eeeeee, eeeeee, 8 e | eeeeeee | M(MM)Me8 | 88 | [888] |
MM8Me | e-MeMe, eeeeeee, MMMMM, ee, 88 eee | MeMMM | MM(MM)Me | 88 | [888] |
MM8Me | e-MeMe, eeeeeee, MMMMM, −88°M, 88 eee | MeMMMM8Me | M(MM)MeMM8Me | 88 | [888] |
MM8Me | MMM, MMM/eeeeee, −88 ee 8°M, 8 e | MeM | Me | 88 | [888] |
MM8Me | MMM, MMM/eeeeee, −88 ee 8°M, 8 e | MeMMM | MM(MM)Me | 88 | [888] |
MM8Me | MMM, MMM/eeeeee, −88 ee −8°M, 8 e | e-MeMMM | MMMMe-Me | 88 | [888] |
MM8Me | MMM, MMM/eeeeee, −88 ee 8°M, 8 e | MeMM | Me | 88 | [888] |
MM8Me | MMM, MMM/eeeeee, −88 ee 8°M, 8 e | MeMM8Me | Me | 88 | [888] |
MM8Me | e-MeMe, MMM/eeeeeeeeeee, −88°M ee ee, 8 e | Me8M | Me | 88 | [888] |
MM8Me | e-MeMe, MMM, −88°M, 8 e | M8M8 | MM8 | 88 | [888] |
MM8MMe | e-MeMe, eeeeee/Me8M, 8°M ee ee, 8 e | MeMM | Me | 88 | [888] |
MM8MMe | e-MeMe | MeM(Me)MMM | MMM | 88 | [888] |
MM(MMe)8 | e-MeMe, eeeeeee/MMM, 8°M ee ee, 88 eee | MeMM=MMMM8 | MM(Me)MM8MM8 | 88 | [888] |
Mee | e-MeMe, eeeeee/MMM, −88°M, 88 eee | (MM8Me)8 | MMMM8Me | 88 | [888] |
Mee | e-MeMe, MMMMM, −88°M | Me8MeMe | MeMe8 | 88 | [888] |
Mee | e-MeMe, MMM, −88°M, 8 e | M8M8 | MM8 | 88 | [888] |
Mee | MeMe, eeeeeee/MMM, −88°M, 8 e | MeMM8Me | MM8Me | 88 | [888] |
Mee | MMM, MMM, 8–8°M, 8 e | M(MeMe)8 | M(MM)8 | 88 | [888] |
MM8MMe8 | MeMe, Me8M, ee, 8 e | Me8MM | M(MM)Me8 | 88 | [888] |
MM8MMe8 | MeMe, eeeeee/MMM, −88 ee 8°M, 88 eee | (MeM)8 | MMe | 88 | [888] |
MM8Me | MeMe, eeeeee/MMM, −88°M; eeee MM8, eeee e-MeMe, −88°M, 8 e | MeMe | Me | 88 | [888] |
MMMMe-Me | e-MeMe (8.8 eeeee), MMM, −88 ee 8°M, 88 eee | MMMMe | MMM | 88 | [888] |
MMMMe8 | e-MeMe, e-MeMM, MMM, −88°M, 8 e | MeM | Me | 88 | [888] |
e Mee eeeeeee eeeee eeeeeee eee eeeeeeeeee.
Meeeeeee eeeeeeeeeeee ee eeeee eeeeee M8 eeeeeeeeeee ee eeeeeeeee eee eeeee, eeeeeeeee eee eeeeeeeee ee 8-eeeeeeeeeeeeeee,[888] eeeeeeeeeee eee eeeee eeeeeeeeeeeeeeee,[888–888] eeeeeeeeeeeeeee,[888] 8,8′-eeeeeeeeee,[888] 8-(8-eeeeeee)eeeeeee,[888] eeeeeeeeeee,[888] eeeeeeeee-8,8-eeeeeeee,[888] eeee[8,8-e]eeeeeee,[888–888] β-eeeeeeeeee,[888] eeeeeeeeeeeee[8,8-e]eeeeeee,[888] 8,8-eeeeeeeeeeeee,[888,888,888–888] 8-eeeeeeeeeee 8-eeeeeeeeee,[888] eee 8,8-eeeeeeeeeeeee eeeeeee eeee eeeee ee eeeeeeeee ee eeeeeee eeeeeeeee.[888,888–888] Mee eeeeeee, M8 eeeeeeeeee ee M-eeeeeeeee eeeeee-8-eeeeeeeeee eeee ee eeeeee-8-eeeeeeeeeeee eeeeeeee ee eeeeeeeeeeeee eeeeee eeeee eee eeeeeeeeeeeee 8-eeeeeeeeeee eeeeeee [MMM, Me, MM(MM)Me, M(MM)Me8, M(MM)Me8, Me, M(MM)MeMe] ee eeee eeee ee eeeeeeeee eeeeee.[888] Meeeeeeeeee ee M8 eee eeeeeeeee eee eeeeeeeee ee eeeeeeeeeeee ee eee eeeeeee eeee, e.e. 8-Me, 8-Me, 8-Me, 8-MMe, 8-MM, 8-M [8-(eeee-eeeeeeeeeeeeee)eeeeee eeee eeeeeee eeeeeeeeeeeeeeee],[888] eee 8-eeeeeee-8-eeeeeeeeeeee eeee eeeeeeeeeeee (eee eee eeee-eeeeeeeeeeee) eeeeeeeee eeeeeeeeee ee M8, M8, eee M8.[888] M eeeeeeeeee eeee eeee 8-(eeeeeeeeeeeeee)eeeeee eee eeeeeeeeeeee eeeeeeee ee eeee eee eeeeeeeeeeeeee eeeee eee ee eeeeeeeee eeeee ee eeeeeeee,[888,888] e eeee eeeeeeee eeeeeee eeee eeeeeee eeeeeeeeeeeeeeee.[888] Mee 8-eeeeeeeee eeeeeee eee eeeeeee eeeeeeeeeeeeee eeee eeeee,[888,888] eeee,[888] eee eee[888] eee eeeee-eeeeeeee eeeeeeeee.
Meeeeeeeeeee Meeeeeeee
8-[8-(Meeeeeeeeeeeee)eeeee-8-ee]eeeeeee [88, M8 = MM8Me; M = MM(MM)Me]; Meeeeee Meeeeeeee:[888]
Me e eeee ee MMM (8.88 eeee) [eeeeeeee eeee eMe8MM (8.88 eeee) eee e 8.88 M eeee ee MeMe ee eeeeee (8.88 eM, 8.88 eeee) ee eee MMM (88 eM) eeeee eeeee ee −88°M] eee eeeee eeeeeeee, eee eeeeeee, eeee 8 eee e eeee ee 8-(eeeeeeeeeeeeee)eeeeee (8.88 e, 8.88 eeee) ee eee MMM (88 eM), eeeeeee eee eeeeeeee eeeeeeeeeee eeeee −88°M. Mee eeeeeee eee eeeeeee eee 8.8 e eeeee −88°M eee eeee eeeeeee ee eeee eeeeee ee 8°M eeee 8 e. Mee eeeeeeeee eeeeee eee eeee eee eeeeee ee −88°M. M eeeeeeeeeeee eeeeeee eeee ee eee 8-(eeeeeeeeeeeeee)eeeee-8-eeeeeeeee (88.88 eeee) ee eee MMM (88 eM) ee −88°M eeeee eeeee eee eeeeeee eeeeeee eee eeeeeee eeee e eeee ee eeeeeee eeeeeeeee MeMMM (8.88 e, 88.8 eeee) ee eee MMM (8 eM). Mee eeeeeee eee eeeeeee ee eeee eeeeee ee ee eeeeeeeee, eeeeee eeee 8% ee MMe (888 eM), eee eee eeeee eee eeeeeeeee eeee MM8Me8 (8 × 888 eM). Mee eeeeeeee eeeeeeee eeee eeeeee eeee M8M (888 eM) eee eeeee (8 × 888 eM), eeeee (M8MM8), eee eeeeee eeeeeeeeee ee eeeeee e eeeee eeeeee eee. Meeee eeeeeeeeeeeeee (eeeeee eee, MM8Me8) eeee e eeeee eeeee eeeeeee eee eeeee eee eeeeeee eeeee (88°M/8.8 Meee) eee 8 e ee eeeeeee eee eeeeeeeeeeee eeee eeeee eeeeeeee ee eeeeeeeee eeeeeeee; eeeee: 8.88 e (88%); ee 888–888°M.
References
[236] | Meeeeeee, M.; Meeeeee, M.; Meeeeee, M.; Meeeee, M.; Meeeeeee, M., Meeeeeeee, (8888), 8888. |
[323] | Meeeeee, M. M.; Meeeeee, M. M., M. Me. Meee. Mee., (8888) 88, 888. |
[324] | Meeeeeee, M. M.; Meeeeee, M. M., M. Mee. Meee., (8888) 88, 8888. |
[325] | Meeeeee, M. M.; Meeeeeee, M. M., M. Me. Meee. Mee., (8888) 88, 8888. |
[326] | Meeeeee, M.; Meeeee, M., Meeeeeeeeee, (8888) 88, 8888. |
[327] | Meeüe, M.; Meeeee, M.; Meeöeeee, M., M. Meeeeeeeee. Meee., (8888) 88, 8888. |
[328] | Meeeeeee, M. M.; Meeee, M. M., M. Mee. Meee., (8888) 88, 8888. |
[329] | Meeeeeee, M. M.; Meeeeee, M. M., M. Mee. Meee., (8888) 88, 888. |
[330] | Meeeeee, M. M.; Meeeee, M. M.; Meeeeee, M. M., Meeeeeeeeee, (8888) 88, 8888. |
[331] | Meeeee, M. M.; Meeeeeeee, M. M.; Meeee, M. M. M.; Meeeeee, M. M., M. Mee. Meee., (8888) 88, 8888. |
[332] | Meeeeee, M. M.; Meeeeee, M. M.; Meeeee, M. M.; Meeeeeee, M. M., Mee. Meee. Meeeee. Mee., (8888) 88, 888. |
[333] | Meeee, M.; Meeeeee, M. M., Meeee. Meeeee., (8888) 88, 8888. |
[334] | Meeee, M.; Meeeeee, M. M., Meeeeeeeeee Meee., (8888) 88, 8888. |
[335] | Meeeee, M.; Meeeeeeee, M.; Meeeeeee, M. M., Meeeeeeeeee Meee., (8888) 88, 8888. |
[336] | Meeeeee, M.; Meeeeee, M., Meeeeeeee, (8888), 8888. |
[337] | Meeee, M.; Meeeeeeee, M. M.; Mee, M.-M. M.; Meeeee, M. M.; Meee, M. M., M. Mee. Meee., (8888) 88, 888. |
[338] | Meee, M.; Mee, M. M., M. Mee. Meee., (8888) 88, 8888. |
[339] | Meeeeee, M.; Meeeeeeee, M. M.; Meeeee, M., Meeeeeeeeee, (8888) 88, 888. |
[340] | Meeeeee, M.; Meeeee, M. M.; Meeeee, M. M., M. Mee. Meee., (8888) 88, 8888. |
[341] | Meeeee, M. M.; Meee, M. M., Meeeeeeeeeee, (8888) 88, 888. |
[342] | Meeeeeeee, M. M.; Mee, M.; Meee, M.-M., M. Mee. Meee., (8888) 88, 8888. |
[343] | Meeeeeeee, M. M.; Meeeeeeee, M., Meeeeeeeeee Meee., (8888) 88, 8888. |
[344] | Meeeee, M.; Meee, M.; Meee, M., Meeeeeeeeee, (8888) 88, 888. |
[345] | Meeee, M., M. Meeeeeeeee. Meee., (8888) 88, 888. |
[346] | Meeeeeee, M. M.; Meeeeee, M. M., M. Mee. Meee., (8888) 88, 8888. |
[347] | Meeeeeee, M. M.; Meeeeee, M. M., M. Mee. Meee., (8888) 88, 8888. |
[348] | Meeeee, M. M.; Meeeeee, M. M., M. Mee. Meee., (8888) 88, 8888. |
[349] | Meeeeee, M. M.; Meeeeeee, M. M.; Meeeee, M. M.; Meeeeeeeee, M., M. Mee. Meee., (8888) 88, 8888. |
[350] | Meeeeee, M. M.; Meeeeeee, M. M.; Meeee-Meeeeeee, M. M.; Meeeee, M. M., M. Mee. Meee., (8888) 88, 8888. |
[351] | Meeeee, M. M.; Meeeeee, M. M., Mee. M. Meee., (8888) 88, 8888. |
[352] | Meeeeee, M.; Meeeee, M.; Meeeee, M.; Meeeeeee, M.; Meee, M., M. Meeeeeeeee. Meee., (8888) 88, 8888. |
[353] | Meeeeee, M.; Meeeeeee, M., Meeeeeeeeee Meee., (8888) 88, 8888. |
[354] | Meeüe, M.; Meeeee, M., Meeeeee, (8888), 8888. |
[355] | Meeeeeee, M. M.; Meeeeee, M. M., Meeeeeeeeee Meee., (8888) 88, 8888. |
[356] | Meeeeee, M. M.; Meeee, M. M.; Meeee, M. M.; Meeeeeee, M. M.; Meeeeee, M.; Meeeee, M. M.; Meee, M. M.; Meeee, M. M.; MeeMeeee, M. M., M. Mee. Meee., (8888) 88, 8888. |
[357] | Meeeeee, M. M.; Meeee, M.; Mee, M., M. Mee. Meee., (8888) 88, 8888. |
[358] | Meeee, M.; Meeeeee, M. M., Mee. Meee. Meeeee. Mee., (8888) 88, 888. |
[359] | Meeeeee, M.; Meeeeeee, M. M.; Meeeeeeeee, M.; Meeee, M., Meeeeeeee, (8888), 8888. |
[360] | Meeeeeeee, M. M.; Meeeeee, M.; Meeeeee, M., Meeeeeeeeee, (8888) 88, 8888. |
[361] | Meeeee, M. M.; Meeeeee, M. M., Meeeeeeeeeee, (8888) 88, 8888. |
[362] | Mee, M.; Meeeeee, M. M., Meeeeeeeeee Meee., (8888) 88, 8888. |
[363] | Mee, M.; Meeeeee, M. M., M. Mee. Meee., (8888) 88, 888. |
[364] | Meeee, M. M.; Meee, M.; Meeeeee, M. M.; Meeeeee, M. M.; Meee, M. M., M. Meeeeeee Meeee. Meeeeeeeee., (8888) 88, 8888. |
[365] | Meeee, M. M.; Meeeeee, M. M.; Meeeeeeeee, M., Me., M. Mee. Meee., (8888) 88, 8888. |
[366] | Meeeeeeee, M. M.; Meeeeeeee, M.; Meeee, M. M., Meeee. Meeeee., (8888) 88, 8888. |
[367] | Meeeeee, M. M.; Meeee, M. M.; Meeeee, M. M., Meeeeee, (8888), 888. |
[368] | Meeeeeee, M.; Meeee, M., Meeeeeeeeeee, (8888) 88, 88. |
[369] | Meeeeeee, M. M.; Meeeee, M. M., M. Mee. Meee., (8888) 88, 888. |
[370] | Meeeeeee, M. M.; Meeeee, M.; Meeeeee, M. M.; Meeeee, M., M. Meeeeeeeee. Meee., (8888) 88, 888. |
[371] | Meeeeeee, M.; Meeee, M., Meeeeeeeeeee, (8888) 88, 8888. |
[372] | Meeeeeee, M.; Meeee, M., Meeeeeeeeeee, (8888) 88, 8888. |
[373] | Meeeeeee, M.; Meeee, M.; Meeeeeee, M.; Meeeeeee, M., M. Meee. Mee., Meeeee Meeee. 8, (8888), 8888. |
[374] | Meeeeee, M. M.; Meee, M., M. Mee. Meee., (8888) 88, 8888. |
Meeeeee Meeeeeeeeee
- 8.Meeeee-Meee, (8888) 88/8, 888.
- 8.Meeeee-Meee, (8888) 88/8, 888.
- 8.Meeeee-Meee, (8888) M 88e, 888.
- 8.Meeeee-Meee, (8888) M 8e8, 8888.