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DOI: 10.1055/s-2007-967982
Rhodium Carbenoid Induced Cycloadditions of Diazo Ketoimides Across Indolyl π-Bonds
Publication History
Publication Date:
08 March 2007 (online)
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Abstract
A series of diazo ketoimides prepared from (1H-indol-3-yl)acetyl chloride and alkyl 2-diazo-3-(3-substituted-2-oxopiperidin-3-yl)-3-oxopropanoates were treated with rhodium(II) acetate. Attack of the imido carbonyl oxygen at the resultant rhodium carbenoid center produced a transient push-pull carbonyl ylide dipole which underwent an intramolecular dipolar cycloaddition across the indole π-bond. In most cases, the resulting cycloadduct is the consequence of endo-cycloaddition with respect to the dipole and this is fully in accord with the lowest energy transition state. Interestingly, when a tert-butyl acetate substituent is located at the ring juncture of the starting diazo ketoimide, the exo-cycloadduct was the exclusive product obtained. In this case, the bulky tert-butyl ester functionality blocks the endo-approach thereby resulting in the cycloaddition taking place from the less congested exo-face.
Key words
rhodium(II) - diazo - catalyst - carbonyl ylide - dipolar cycloaddition - indole - kopsifoline - alkaloid
- 1
Comprehensive Heterocyclic Chemistry
Katritzky A.Rees CW.Scriven EF. Elsevier Science; Oxford, UK: 1996. -
2a
Martin SF. In The Alkaloids Vol. 30:Brossi A. Academic Press; New York: 1987. p.251-377 -
2b
Lewis JR. Nat. Prod. Rep. 1994, 11: 329 -
2c
Jeffs PW. In The Alkaloids Vol. 19:Rodrigo RGA. Academic Press; New York: 1981. p.1-80 -
3a
Kuehne ME.Matsko TH.Bohnert JC.Motyka L.Oliver-Smith D. J. Org. Chem. 1981, 46: 2002 -
3b
Kuehne ME.Earley WG. Tetrahedron 1983, 39: 3707 -
3c
Kuehne ME.Brook CS.Xu F.Parsons R. Pure Appl. Chem. 1994, 66: 2095 -
3d
Nkiliza J.Vercauteren J. Tetrahedron Lett. 1991, 32: 1787 -
3e
Rawal VH.Michoud C.Monestel RF. J. Am. Chem. Soc. 1993, 115: 3030 -
4a
Overman LE.Sworin M.Burk RM. J. Org. Chem. 1983, 48: 2685 -
4b
Overman LE.Sugai S. Helv. Chim. Acta 1985, 68: 745 -
4c
Overman LE.Robertson GM.Robichaud AJ. J. Org. Chem. 1989, 54: 1236 -
5a
Gallagher T.Magnus P.Huffman JC. J. Am. Chem. Soc. 1983, 105: 4750 -
5b
Magnus P.Gallagher T.Brown P.Pappalardo P. Acc. Chem. Res. 1984, 17: 35 -
6a
Rigby JH.Qabar MN. J. Org. Chem. 1993, 58: 4473 -
6b
Rigby JH.Qabar M.Ahmed G.Hughes RC. Tetrahedron 1993, 49: 10219 -
6c
Rigby JH.Hughes RC.Heeg MJ. J. Am. Chem. Soc. 1995, 117: 7834 -
6d
Rigby JH.Mateo ME. Tetrahedron 1996, 52: 10569 -
6e
Rigby JH.Laurent S.Cavezza A.Heeg MJ. J. Org. Chem. 1998, 63: 5587 -
7a
Kraus GA.Thomas PJ.Bougie D.Chen L. J. Org. Chem. 1990, 55: 1624 -
7b
Sole D.Bonjoch J. Tetrahedron Lett. 1991, 32: 5183 -
7c
Bonjoch J.Sole D.Bosch J. J. Am. Chem. Soc. 1993, 115: 2064 -
7d
Schultz AG.Holoboski MA.Smyth MS. J. Am. Chem. Soc. 1993, 115: 7904 -
7e
Schultz AG.Guzzo PR.Nowak DM. J. Org. Chem. 1995, 60: 8044 -
7f
Schultz AG.Holoboski MA.Smyth MS. J. Am. Chem. Soc. 1996, 118: 6210 -
8a
Pearson WH.Postich MJ. J. Org. Chem. 1994, 59: 5662 -
8b
Padwa A.Price AT. J. Org. Chem. 1995, 60: 6258 -
9a
Takano S.Inomata K.Ogasawara K. Chem. Lett. 1992, 443 -
9b
Uesaka N.Saitoh F.Mori M.Shibasaki M.Okamura K.Date T. J. Org. Chem. 1994, 59: 5633 -
9c
Mori M.Kuroda S.Zhang CS.Sato Y. J. Org. Chem. 1997, 62: 3263 -
10a
Tietze LF.Beifuss U. Angew. Chem., Int. Ed. Engl. 1993, 32: 131 -
10b
Tietze LF. Chem. Rev. 1996, 96: 115 -
11a
Ho TL. Tandem Organic Reactions Wiley; New York: 1992. -
11b
Bunce RA. Tetrahedron 1995, 51: 13103 -
11c
Parsons PJ.Penkett CS.Shell AJ. Chem. Rev. 1996, 96: 195 - 12
Ziegler FE. In Comprehensive Organic Synthesis, Combining C-C π-Bonds Vol. 5:Paquette LA. Pergamon Press; Oxford: 1991. Chap. 7.3. - 13
Waldmann H. Domino Reactions In Organic Synthesis Highlights IIWaldmann H. VCH; Weinheim: 1995. p.193-202 - 14
Curran DP. In Comprehensive Organic Synthesis Vol. 4:Trost BM.Fleming I. Pergamon; Oxford: 1991. p.779 -
16a
Padwa A.Austin DJ.Hornbuckle SF.Semones MA.Doyle MP.Protopopova MN. J. Am. Chem. Soc. 1992, 114: 1874 -
16b
Padwa A.Austin DJ.Price AT.Semones MA.Doyle MP.Protopopova MN.Winchester WR. J. Am. Chem. Soc. 1993, 115: 8669 -
16c
Padwa A.Austin DJ.Hornbuckle SF.Price AT. Tetrahedron Lett. 1992, 33: 6427 -
16d
Padwa A. Acc. Chem. Res. 1991, 24: 22 -
16e
Padwa A.Carter SP.Nimmesgern H. J. Org. Chem. 1986, 51: 1157 -
16f
Padwa A.Carter SP.Nimmesgern H.Stull PD. J. Am. Chem. Soc. 1988, 110: 2894 -
16g
Padwa A.Stull PD. Tetrahedron Lett. 1987, 28: 5407 -
16h
Padwa A.Fryxell GE.Zhi L. J. Org. Chem. 1988, 53: 2877 -
16i
Padwa A.Chinn RL.Zhi L. Tetrahedron Lett. 1989, 30: 1491 -
16j
Padwa A.Hornbuckle SF.Fryxell GE.Stull PD. J. Org. Chem. 1989, 54: 817 -
16k
Dean DC.Krumpe KE.Padwa A. J. Chem. Soc., Chem. Commun. 1989, 921 -
16l
Padwa A.Chinn RL.Hornbuckle SF.Zhi L. Tetrahedron Lett. 1989, 30: 301 -
16m
Padwa A.Sandanayaka VP.Curtis EA. J. Am. Chem. Soc. 1994, 116: 2667 -
16n
Curtis EA.Sandanayaka VP.Padwa A. Tetrahedron Lett. 1995, 36: 1989 - 17
Padwa A.Hornbuckle SF. Chem. Rev. 1991, 91: 263 - 18
Padwa A.Weingarten MD. Chem. Rev. 1996, 96: 223 -
19a
Padwa A.Brodney MA.Marino JP.Sheehan SM. J. Org. Chem. 1997, 62: 78 -
19b
Padwa A.Precedo L.Semones M. J. Org. Chem. 1999, 64: 4079 -
19c
Padwa A.Curtis EA.Sandanayaka VP. J. Org. Chem. 1997, 62: 1317 -
20a
Kinder FR.Bair KW. J. Org. Chem. 1994, 59: 6965 -
20b
Chen B.Ko RYY.Yuen MSM.Cheng K.-F.Chiu P. J. Org. Chem. 2003, 68: 4195 -
20c
Hodgson DM.Avery TD.Donohue AC. Org. Lett. 2002, 4: 1809 -
20d
Dauben WG.Dinges J.Smith TC. J. Org. Chem. 1993, 58: 7635 -
21a
Padwa A.Price AT. J. Org. Chem. 1995, 60: 6258 -
21b
Padwa A.Price AT. J. Org. Chem. 1998, 63: 556 - 22
Padwa A.Hertzog DL.Nadler WR. J. Org. Chem. 1994, 59: 7072 -
23a
Cordell GA. In The Alkaloids Vol. 17:Manske RHF.Rodrigo RGA. Academic Press; New York: 1979. p.199-384 -
23b
Saxton JE. Nat. Prod. Rep. 1993, 10: 349 -
24a
Kam T.-S.Choo Y.-M. Tetrahedron Lett. 2003, 44: 1317 -
24b
Kam T.-S.Choo Y.-M. Phytochemistry 2004, 65: 2119 -
24c
Kam T.-S.Choo Y.-M. Helv. Chim. Acta 2004, 87: 991 -
25a
Mejía-Oneto JM.Padwa A. Tetrahedron Lett. 2004, 45: 9115 -
25b
Mejia-Oneto JM.Padwa A. Org. Lett. 2004, 6: 3241 -
25c
Padwa A.Boonsombat J.Rashatasakhon P.Willis J. Org. Lett. 2005, 7: 3725 -
25d
Padwa A.Lynch SM.Mejia-Oneto JM.Zhang H. J. Org. Chem. 2005, 70: 2206 - 26 For an early approach toward the kopsifolines, see:
Hong X.France S.Mejia-Oneto JM.Padwa A. Org. Lett. 2006, 8: 5141 - 27
Marino JP.Osterhout MH.Price AT.Sheehan SM.Padwa A. Tetrahedron Lett. 1994, 35: 849 -
29a
Regitz M. Chem. Ber. 1966, 99: 3128 -
29b
Regitz M.Hocker J.Liedhegener A. Org. Synth. 1973, 5: 179 - 31
Muthusamy S.Gunanatha C.Babu SA. Tetrahedron Lett. 2001, 42: 523
References and Notes
Frontiers in Organic Synthesis; Wender, P. A., Ed.; Chem. Rev. 1996, 96, 1-600.
28In a typical general procedure, 1.1 equiv of the appropriate 3-indoleacetic acid was dissolved in CH2Cl2 and 4.0 equiv of oxalyl chloride was added dropwise. The solution was stirred overnight and then concentrated under reduced pressure. The resulting solid was taken up in THF, which was immediately added to a vigorously stirred mixture containing 1.0 equiv of the diazo lactam (i.e. 19 or 20) and 4 Å MS in THF. After stirring for 12 h, the mixture was filtered through a pad of Celite® and concentrated under reduced pressure. The crude material was purified by flash silica gel column chromatography to give the desired coupled product. Using this procedure, 3-{3-(2-benzyloxyethyl)-1-[2-(1-methyl-1H-indol-3-yl)acetyl]-2-oxopiperidin-3-yl}-2-diazo-3-oxopropionic acid methyl ester (16d) was obtained as a colorless oil in 82% yield. IR (neat): 2143, 1718, 1685, 1332, 1146 cm-1. 1H NMR (400 MHz, CDCl3): δ = 1.65-1.75 (m, 1 H), 1.85-2.02 (m, 2 H), 2.19-2.30 (m, 3 H), 3.46-3.53 (m, 1 H), 3.61-3.80 (m, 2 H), 3.70 (s, 3 H), 3.76 (s, 3 H), 4.15-4.21 (m, 1 H), 4.24 (s, 2 H), 4.37 (d, 1 H, J = 15.8 Hz), 4.41 (d, 1 H, J = 15.8 Hz), 6.88 (s, 1 H), 7.07-7.11 (m, 1 H), 7.17-7.32 (m, 7 H), 7.54 (d, 1 H, J = 8.0 Hz). 13C NMR (100 MHz, CDCl3): δ = 19.5, 30.2, 32.7, 34.7, 35.5, 44.5, 52.5, 59.3, 67.2, 73.0, 107.9, 109.3, 119.1, 119.2, 121.6, 127.6, 127.7, 128.2, 128.3, 128.5, 136.9, 138.4, 161.6, 173.6, 176.4, 190.8.
To a solution of 0.2 g of the diazoimide 16d in 10 mL of benzene under N2 was added 2 mg rhodium(II) acetate, and the mixture was heated at reflux for 1 h. The mixture was allowed to cool to r.t. and was filtered through a pad of Celite®. The solvent was removed under reduced pressure and the residue was subjected to flash silica gel chromatog-raphy to give 0.16 g (96%) of the dipolar-cycloaddition product 21d.
The X-ray crystal structure analysis will be reported elsewhere.