人 1. BuLi THF 0C CF?CF3 92% Neu2.(CO2Et2-78℃0 59-87% 2M HCI DME 79-89% R=H. 4-OMe, 4,5-diOMe, 7-F, 5-CF3, 6-CF3 34-82% R=HB Scheme 23 =H OMe intermediate is an acyllithium species which cyclizes onto the urea carbonyl group. This lithiation-carbonylation strategy was Scheme 19 adapted to the synthesis of 3-hydroxyoxindoles by the lithiatic of N-pivaloylanilines. Smith and co-workers have alse 1 BuLi THF employed the original Wender indole synthesis to the synthesis of N-dimethylurea-protected indoles involving the dilithiation HBoc 2. R'CONMeR of N-phenyl-N, N-dimethylurea. 7 6384% R=H Me 3. 4 Couture indole svnthesis R"=Me, OMe No new examples were reported since the last review Scheme 20 3.5 Smith indole synthesis The Smith indole synthesis, which involves dilithiation of N-trimethylsilyl-o-toluidine and subsequent reaction with a N二PPh non-enolizable ester to afford the 2-substituted indole has been 48-74% used to synthesize 2-trifluoromethylindole in 47% yield by quenching the above mentioned dianion with ethyl trifluor acetate SOR R=Ph, p-Tol 3.6 Kihara indole svnthesis 80-90°C R= Ph, p-Tol Kihara et al. have described an indole ring formation that involves an intramolecular Barbier reaction of phenyl and alkyl N-(2-lodophenyl)-N-methylaminomethyl ketones as summarized in Scheme 24. 2 The hydroxyindoline by-product if obtained, can be converted to the indole with aqueous CO, Me HCI R= Me, Cg H11, Ph (+17-29% of the 3.7 Nenitzescu indole synthesis The past five years have seen a resurrection of the Nenitzescu 3.2 Schmid indole svnthesis indole synthesis and this classic sequence was used to construct No new examples were uncovered since the last review. methyl 5-hydroxy-2-methoxymethylindole-3-carboxylate, the ey intermediate in a synthesis of the antitumor indolequinor 3.3 Wender indole svnthesis Eo 9. 2 This reaction has also been used to prepare a series of -aryl-5-hydroxyindoles, 2 and it was utilized in the synthesis The Wender indole synthesis, which involves the ortho- of a key indole(Scheme 25)used to prepare potent and selectiv lithiation of N-phenylamides followed by reaction of the s-PLA2 inhibitors 23 resulting dianion with a-haloketones and subsequent ring closure and dehydration, has been extended to a convenient COMe Thesis of isatins by quenching with diethyl pyruvate Scheme 23). 14 MeNO 2 A related isatin synthesis has been described by Smith and co-workers> that involves the carbonylation of the dianion derived from N'-(2-bromoaryl)-N, N-dimethylureas. The key 1050 J. Chem. Soc.. Perkin Trans. 1. 2000. 1045-10751050 J. Chem. Soc., Perkin Trans. 1, 2000, 1045–1075 3.2 Schmid indole synthesis No new examples were uncovered since the last review. 3.3 Wender indole synthesis The Wender indole synthesis,113 which involves the ortho￾lithiation of N-phenylamides followed by reaction of the resulting dianion with α-haloketones and subsequent ring closure and dehydration, has been extended to a convenient synthesis of isatins by quenching with diethyl pyruvate (Scheme 23).114 A related isatin synthesis has been described by Smith and co-workers 115 that involves the carbonylation of the dianion derived from N-(2-bromoaryl)-N,N-dimethylureas. The key Scheme 19 Scheme 20 Scheme 21 Scheme 22 intermediate is an acyllithium species which cyclizes onto the urea carbonyl group. This lithiation–carbonylation strategy was adapted to the synthesis of 3-hydroxyoxindoles by the lithiation of N-pivaloylanilines.116 Smith and co-workers have also employed the original Wender indole synthesis to the synthesis of N-dimethylurea-protected indoles involving the dilithiation of N-phenyl-N,N-dimethylurea.117 3.4 Couture indole synthesis No new examples were reported since the last review. 3.5 Smith indole synthesis The Smith indole synthesis,118 which involves dilithiation of N-trimethylsilyl-o-toluidine and subsequent reaction with a non-enolizable ester to afford the 2-substituted indole, has been used to synthesize 2-trifluoromethylindole in 47% yield by quenching the above mentioned dianion with ethyl trifluoro￾acetate.119 3.6 Kihara indole synthesis Kihara et al. have described an indole ring formation that involves an intramolecular Barbier reaction of phenyl and alkyl N-(2-iodophenyl)-N-methylaminomethyl ketones as summarized in Scheme 24.120 The hydroxyindoline by-product, if obtained, can be converted to the indole with aqueous HCl. 3.7 Nenitzescu indole synthesis The past five years have seen a resurrection of the Nenitzescu indole synthesis and this classic sequence was used to construct methyl 5-hydroxy-2-methoxymethylindole-3-carboxylate, the key intermediate in a synthesis of the antitumor indolequinone EO 9.121 This reaction has also been used to prepare a series of N-aryl-5-hydroxyindoles,122 and it was utilized in the synthesis of a key indole (Scheme 25) used to prepare potent and selective s-PLA2 inhibitors.123 Scheme 23 Scheme 24 Scheme 25