An Improved Synthetic Route to Angularly Functionalized Hydrofluorene Derivatives through Pd(0)-Catalyzed Heck Reaction

Abstract

4a-Substituted 1,1-dimethyl or 1-carbomethoxy-1-methyl hydrofluorenes carrying various substituents in the aromatic ring could be conveniently synthesized by Pd(0)-catalyzed Heck reaction. The required bromobenzyl-substituted ethylidene cyclohexane substrates were derived from Hagemann’s ester (methyl analogue) via condensation with appropriate benzyl bromide, hydrolytic decarboxylation of the ester, 1,4-addition of methyl or cyano group followed by necessary functional group manipulation, and Wittig olefination. Simple organic transformations converted the vinyl group to carboxy, formyl or hydroxymethyl. The ring juncture stereochemistry of the products could be ascertained by correlation approach.

Key words

4a-substituted hydrofluorenes - Heck reaction - Wittig reaction - Hagemann’s ester

References

• 1 Parham WE. Czuba LJ. J. Org. Chem.  1969,  34:  1899 
• 2 Ghosh S. Ghatak UR. J. Org. Chem.  1980,  46:  1486 
• 3 Trost BM. Walchli R. J. Am. Chem. Soc.  1987,  109:  3487 
• 4a Banerjee M. Mukhopadhyay R. Achari B. Banerjee AK. Org. Lett.  2003,  5:  3931 
• 4b Sengupta S. Mukhopadhyay R. Achari B. Banerjee AK. Tetrahedron Lett.  2005,  46:  1515 
• 4c Sengupta S. Drew GB. Mukhopadhyay R. Achari B. Banerjee AK. J. Org. Chem.  2005,  70:  7694 
• 5 Miyano S. Fukushima H. Inagawa H. Hashimoto H. Bull. Chem. Soc. Jpn.  1986,  59:  3285 
• 6 Pal S. Mukhopadhyay JK. Ghatak UR. J. Org. Chem.  1994,  59:  2687 
• 7 Berger DM. Brinberg G. DeMorin F. Dutia M. Powell D. Wang YD. Synthesis  2003,  1712 
• 8 Banik BK. Chakraborti AK. Ghatak UR. J. Chem. Res., Synop.  1986,  406 ; J. Chem. Res., Miniprint 1986, 3391
• 9 Ghatak UR. Chakravarty J. Banerjee AK. Tetrahedron  1968,  24:  1577 
• 10 Chakraborti AK. Basak A. Grover V. J. Org. Chem.  1999,  64:  8014 
• 11a Mori M. Uozumi Y. Kimura M. Ban Y. Tetrahedron  1986,  42:  3793 
• 11b Maercker A. Org. React. (N.Y.)  1965,  14:  270 
• 12 Link JT. Org. React. (N.Y.)  2002,  60:  157 ; and references cited therein
• 13 Clive DLJ. Wang J. J. Org. Chem.  2004,  69:  2773 
• 14 Konoike T. Matsumura K. Yorifuji T. Shinomoto S. Ide Y. Ohya T. J. Org. Chem.  2002,  67:  7741 
• 15 Mukhopadhyaya JK. Pal S. Ghatak UR. Synth. Commun.  1995,  25:  1641 
• 16a Kocienski PJ. Cernigliaro G. Feldstein G. J. Org. Chem.  1977,  42:  353 
• 16b Hayashi H. Nakanishi K. Brandon C. Marmur J. J. Am. Chem. Soc.  1973,  95:  8749 
• 17 Nakamura E. Inubushi T. Aoki S. Machii D. J. Am. Chem. Soc.  1991,  113:  8980