of starting material. AcOH (1 ml) was added carefully and when the foaming subsided, the flask was stoppered and heated to 80¡ãC for 2 h. The crude reaction mixture was then eluted onto a Dowex 50 (H+) column (2.7 x 10 cm), washed with H2O (150 ml), then eluted with 1 M NH4OH (200 ml). Ninhydrin-active fractions were collected and pooled for freeze drying, and thus afforded compound 2 (0.2 g, 89%) as an ammonium salt.
Page 48 of 77
3.2 ¶Ô¼×±½»Çõ£»ù£¨Tos£©
¶Ô¼×±½»Çõ£°·Óɰ·ºÍ¶Ô¼×±½»Çõ£ÂÈÔÚßÁऻòË®ÈÜÐÔ¼î´æÔÚÏÂÖÆµÃµÄ£¬ËüÊÇ×îÎȶ¨µÄ°±»ù±£»¤»ùÖ®Ò»£¬¶Ô¼îÐÔË®½âºÍ´ß»¯»¹ÔÎȶ¨¡£¼îÐÔ½ÏÈõµÄ°·ÈçßÁ¿©ºÍßÅßáÐγɵĶԼױ½»Çõ£°·±È¼îÐÔ¸üÇ¿µÄÍé»ù°·ËùÐγɵĶԼױ½»Çõ£°·¸üÒ×È¥±£»¤£¬¿ÉÒÔͨ¹ý¼îÐÔË®½âÈ¥±£»¤£¬¶øºóÕßͨ¹ý¼îÐÔË®½âÈ¥±£»¤ÊDz»¿ÉÄܵġ£¶Ô¼×±½»Çõ£°·Ò»¸öºÜÓÐÎüÒýÁ¦µÄÐÔÖÊÊÇÕâЩÑÜÉúÎïµÄõ£°·»ò°±»ù¼×Ëáõ¥¸üÈÝÒ×Ðγɽᾧ¡£³ýÔÚÔçÆÚ×÷¹ý¦Á-°±»ùµÄ±£»¤»ùÍ⣬һ°ã¶¼ÊÇÓÃ×÷¼îÐÔ°±»ùËáµÄ²àÁ´±£»¤»ù¡£
Tos-°±»ùËáÄܹ»Í¨¹ýõ£ÂÈ¡¢µþµª¡¢DCCºÍËÄÒÒ»ù½¹ÑÇÁ×ËáµÈ·½·¨½øÐнÓëÄ£¬µ«»ìºÏËáôû·¨Ò»°ã²»ÄܲÉÓá£ÕâÊÇÒòΪTos»ùµÃÇ¿ÁÒÎüµç×ÓЧӦʹµÃ±»õ£»¯µÄ°±»ùÉϵÄÇâÔ×ÓÈÝÒ×ÀëÈ¥£¬¶øÔÚÓûìºÏËáôû·¨½ÓëÄʱ»á²úÉúN£¬N-˫ȡ´úµÈ¸±·´Ó¦Ê¹²úÂʺܵ͡£Í¬Ñù£¬Tos-°±»ùËáµÄõ£ÂÈÔÚNaOHµÈÇ¿¼î×÷ÓÃϺܲ»Îȶ¨£¬»á·¢Éú·Ö½âÉú³ÉTos-NH2¡¢È©ºÍCO£¨¼ûÏÂʽ£©[1]
RClOCH2ONHTosNaOHClOCRN-TosNa++H2ORNTos+CO+NaClTos-NH2+RCHO+CO+NaCl
1. A. F. Beecham., Chem. Ind., (London)., 1955, 1120; J. Am. Chem. Soc., 1957, 79, 3257
3.2.1 ¶Ô¼×±½»Çõ£»ùµÄÒýÈë
¶Ô¼×±½»Çõ£ÂÈÔÚNaOH¡¢NaHCO3»òÆäËûÓлú¼î´æÔÚÏÂͬ°±»ùËá¡¢ßÁ¿©ºÍßÅßáµÈ·´Ó¦ºÜÈÝÒ׵õ½Á¼ºÃ²úÂʵÄTos-ÑÜÉúÎï[1]
1. S. Sakakibara, T. Fujii., Bull. Chem. Soc. Jpn., 1969, 42, 1466
3.2.1.1¶Ô¼×±½»Çõ£»ùµÄÒýÈëʾÀý
ONHNH21Et3N, THFHCOOMeOTsClNNHTs2COOMe
Arthur G. Schultz and Carlos W. Alva., Org. Syn., 73, 174
22.9 g (90 mmol) of compound 1 , 13.66 g (135 mmol) of triethylamine, and 100 mL of dry THF are
Page 49 of 77
placed in a 300-mL, round-bottomed flask, equipped with a pressure-equalizing dropping funnel, a magnetic stirring bar, and a nitrogen inlet. The dropping funnel is charged with a solution of
18.9 g (99.1 mmol) of p-toluenesulfonyl chloride in 50 mL dry THF. The reaction mixture is cooled
to 0¡ãC with magnetic stirring, and the solution of p-toluenesulfonyl chloride is delivered dropwise over a 30-min period. The resulting cloudy solution is stirred for 60 hr at ambient temperature. After this time period, the reaction mixture is diluted with 50 mL of saturated
sodium chloride solution and 50 mL of ethyl acetate, transferred to a 500-mL separatory funnel,
mixed thoroughly, and the organic phase separated. The aqueous phase is extracted twice with
50 mL of ethyl acetate. The combined organic layers are dried (Na2SO4), filtered, concentrated
under reduced pressure, and the resulting residue purified by chromatography to give 22.43 g (61%) of compound 2 (Rf = 0.34, CHCl3/EtOAc, 1:1) as a colorless solid, mp 144¨C146¡ãC.
3.2.2 ¶Ô¼×±½»Çõ£»ùµÄÍÑÈ¥
Tos·Ç³£Îȶ¨£¬Ëü¾µÃÆðÒ»°ãËá½â(TFAºÍHClµÈ£©¡¢Ôí»¯¡¢´ß»¯Çâ½âµÈ¶àÖÖÌõ¼þµÃ´¦Àí±ÈÊÜÓ°Ï죬³£ÓÃÝÁÄÆ[1]¡¢Na/NH3(Òº) [2] ºÍ Li/NH3(Òº) [3]´¦ÀíÍÑÈ¥¡£HBr/±½·Ó[4]ºÍMg/MeOH Ò²ÊDZȽϺõÄÈ¥±£»¤·½·¨[5]¡£ÖµµÃ×¢ÒâµÄÊÇ£¬Na/NH3(Òº)µÄ²Ù×÷±È½ÏÂé·³£¬²¢ÇÒ»áÒýÆðһЩëļüµÄ¶ÏÁѺÍëÄÁ´µÄÆÆ»µ¡£ÁíÍ⣬ÓÐʱHF/MeCN»ØÁ÷Ò²ÄÜÍÑÈ¥Tos»ù
[6]
¡£
1. Masuda, Yui; Mori, Kenji et al., Biosci. Biotechnol. Biochem., 2002, 66(7), 1531-1537; Kaiser, Alexander; Balbi, Miriam et al., Tetrahedron: Asymmetry, 1999, 10(5), 1001-1014; Takikawa, Hirosato; Muto, Shiu-etsu et al., Tetrahedron, 1998, 54(13), 3141-3150; Sugimura, Hideyuki; Miura, Masayuki et al., Tetrahedron: Asymmetry, 1997, 8(24), 4089-4100
2. J. Kovacs, U. R. Ghatak., Chem. Ind. (London)., 1963, 913; Dolence, E. Kurt; Roylance, Jason B et al., Tetrahedron: Asymmetry, 2004, 15(20), 3307-3322; Amat, Mercedes; Seffar, Fatima et al., Synthesis, 2001, 2, 267-275; Hoye, Thomas R; Chen, Minzhang et al., Tetrahedron Lett., 1996, 37(18), 3099-3100; Hoye, Thomas R; Chen, Minzhang et al., J. Org. Chem., 1999, 64(19), 7184-7201
3. Burgess, Kevin; Liu, Lee T et al., J. Org. Chem., 1993, 58(17), 4758-4763
4. Kotek, Jan; Lebduskova, Petra et al., Chem. Europ. J., 2003, 9(23), 5899-5915; Calvisi,
Page 50 of 77
Giuseppina; Dell-Uomo, Natalina et al., Eur. J. Org. Chem., 2003, 23, 4501-4506; Currie, Gordon S; Drew, Micheal G. B et al., J. Chem. Soc. Perkin Trans. 1, 2000, 17, 2982-2990; Davis, Franklin A; Srirajan, Vaidyanathan et al., J. Org. Chem., 2000, 65(10), 3248-3251; Davis, Franklin A; Liu, Hu et al., J. Org. Chem., 1999, 64(20), 7559-7567; Drury, William J; Ferraris, Dana et al., J. Am. Chem. Soc., 1998, 120(42), 11006-11007
5. Y. Yokoyama, T. Matsumoto et al., J. Org. Chem., 1995, 60, 1486; B. Nyasse, L. Grehn et al., J. Chem. Soc. Chem. Commun., 1997, 1017; Nenajdenko, Valentine G; Karpov, Alexei S et al., Tetrahedron: Asymmetry, 2001, 12(18), 2517-2528
6. Takikawa, Hirosato; Maseda, Takeshi et al., Tetrahedron Lett., 1995, 36(42), 7689-7692
3.1.2.1 Na/NH3Íѳý¶Ô¼×±½»Çõ£»ùʾÀý
TosHNH1 Na/NH3OHOHH2NH2OHOH
A. Schrey; F. Osterkamp et al., Eur. J. Org. Chem., 1999, 11, 2977
To a two necked flask equipped with a dry ice condenser was added compound 1 (3.20 g, 10.1 mmol) in THF (15 ml) and ammonia gas to condense about 25 ml of liquid. Small pieces of sodium (552 mg, 24.2 mmol) were added to the stirred solution until a blue color color persisted for 5 min. After stirring for 10 min, the reaction was quenched by adding dropwise glacial acetic acid (2 ml). The NH3 was allowed to evaporate. The crude product was dried in vacuo for 1 h to give compound 2 (1.3 g, 89%) as a colorless oil.
Li/NH3Íѳý¶Ô¼×±½»Çõ£»ùʾÀý
NHTosOH12Li/NH3NH2OH
Burgess, Kevin; Liu, Lee T et al., J. Org. Chem., 1993, 58(17), 4758-4763
Lithium metal was added to a solution of compound 1 (1.5 g, 5.01 mmol) in 5 ml of THF and 200 ml of liquid NH3. The resulting dark blue solution was stirred for 1 h and then quenched with 1 ml of absolute ethanol. The ammonia was evaporated. The residue was diluted with saturated aqueous NaCl (30 ml), and extracted with CH2Cl2 (4 x 20 ml). The combined layers was dried and the solvent evaporated to give compound 2 (0.4 g, 55%) as oil.
Page 51 of 77