Abstract
Preparations of 2,3,4,5-tetrahydro-1,5-methano-1H -3-benzazepine (5 ) from benzonorbornadiene (1 ) by oxidative cleavage and reductive amination sequences were investigated. Osmium-mediated dihydroxylation of 1 followed by NaIO4 cleavage, reductive amination and debenzylation provides 5 in 64-73% yield overall in three operations. A tandem ozonolysis-reductive amination procedure gives 5 as the tosylate salt from benzonorbornadiene with no isolation of intermediates in 28% yield.
Key words
oxidation - ozonolysis - amination - reduction - bicyclic compounds
References
1 Wittig G.
Knauss E.
Chem. Ber.
1958,
91:
895
2 Mazzocchi PH.
Stahly BC.
J. Med. Chem.
1979,
22:
455
3a Coe J.
Org. Lett.
2000,
2:
4205
3b Bashore CG.
Samardjiev IJ.
Bordner J.
Coe JW.
J. Am. Chem. Soc.
2003,
125:
3268
4 VanRheenen V.
Cha DY.
Hartley WM.
Org. Synth.
1988,
6:
342
N -oxide did not improve the rate and contributed volatile NMe3 to the side stream:
5a Nomura K.
Okazaki K.
Hori K.
Yoshii E.
J. Am. Chem. Soc.
1987,
109:
3402
5b Ray R.
Matteson DS.
Tetrahedron Lett.
1980,
21:
449
5c Lodge EP.
Heathcock CH.
J. Am. Chem. Soc.
1987,
109:
3353
6 This process could be initiated by adding seed crystals of 6 .
7 As an additional benefit of this preparation, the osmium containing filtrate, after partial concentration, could be reused with fresh benzonorbornadiene, NMO and solvent.
8a Gypser A.
Michel D.
Nirschl DS.
Sharpless KB.
J. Org. Chem.
1998,
63:
7322
8b Dupau P.
Epple R.
Allen AT.
Fokin VV.
Sharpless KB.
Adv. Synth. Catal.
2002,
344 No. 3/4:
421
9 1 successfully achieved rapid conversion under the known conditions; however, the stoichiometric manganese salts were difficult to separate from the highly crystalline diol 6 . See: Ogino T.
Tetrahedron Lett.
1980,
21:
177
10 An alternative method with sodium chlorite-K2 OsO4 ·2H2 O achieved more rapid conversion in slightly lower yield. See experimental details.
11 Abdel-Magid AF.
Carson KG.
Harris BD.
Maryanoff CA.
Shah RD.
J. Org. Chem.
1996,
61:
3849
12a Hartung WH.
Simonoff R.
Org. React.
1953,
7:
263
12b Jung ME.
Longmei Z.
Tangsheng P.
Huiyan Z.
Yan L.
Jingyu S.
J. Org. Chem.
1992,
57:
3528
13a Criegee R.
Schroeder G.
Chem. Ber.
1960,
93:
689
13b Schreiber SL.
Claus RE.
Reagan J.
Tetrahedron Lett.
1982,
23:
3867
13c Thompson QE.
J. Org. Chem.
1962,
27:
4498
13d Criegee R.
Angew. Chem., Int. Ed. Engl.
1975,
14:
745
13e Lee DG.
Chen T. In
Comprehensive Organic Synthesis
Vol. 7:
Trost BM.
Pergamon Press;
Oxford:
1991.
p.541-591
14 Pollart KA.
Miller RE.
J. Org. Chem.
1962,
27:
2392
15 White RW.
King SW.
O’Brien JL.
Tetrahedron Lett.
1971,
12:
3591
16 The reduction of the hydroperoxide 9 , reductive amination of 10 and N -benzyl cleavage of 8 to 5 could all be executed in a single pot using 10% Pd/C as the sole catalyst for hydrogenolysis and p -toluene sulfonic acid (rather than HCOOH or HOAc for the reductive amination). Because the activity of Pd/C was relatively higher than Pt/C and p -toluene sulfonic acid was less optimal than HCOOH for the reductive amination, the yield suffered (14-16%).
17 Coe JW.
Wirtz MC.
Bashore CG.
Candler J.
Org. Lett.
2004,
6:
1589
