Coupling of β-Cyanocarbene-Chromium Complexes with 2-Alkynylbenzoyl Derivatives: A [5+5]-Cycloaddition Approach to Phenanthridines

Abstract

The coupling of β-cyanocarbene complexes and 2-alkynylbenzoyl derivatives has been examined. The reaction afforded phenanthridine derivatives in a complex tandem process involving carbene-alkyne coupling, isobenzofuran formation, intramolecular Diels-Alder reaction using a nitrile dienophile, and deoxygenation. The chemistry could not be reproduced in non-chromium-based systems.

Key words

carbene complexes - chromium - cycloadditions - alkynes - nitriles - Diels-Alder reactions

References

• 1 For a preliminary account of this work, see: Ghorai BK. Jiang D. Herndon JW. Org. Lett.  2003,  5:  4261 
• 2a For the latest examples of this reaction, see: Li R. Zhang L. Camacho-Davila A. Herndon JW. Tetrahedron Lett.  2005,  46:  5117 
• 2b For the first example, see: Jiang D. Herndon JW. Org. Lett.  2000,  2:  1267 
• Most examples involve electron-deficient nitriles; recent examples include:
• 3a Volle JN. Schlosser M. Eur. J. Org. Chem.  2002,  1490 
• 3b Junge H. Oehme G. Tetrahedron  1998,  54:  11027 
• 4 Diels-Alder adducts have only been characterized by combustion analysis and IR spectra, and other structural alternatives were not considered: Tagmazyan KT. Mkrtchyan RS. Babayan AT. J. Org. Chem. USSR  1974,  10:  1657 
• 5 Hassner A. Fischer B. Heterocycles  1993,  35:  1441 
• 6 Whitney SE. Winters M. Rickborn B. J. Org. Chem.  1990,  55:  929 
• 7 For a related process using α-bromoesters, see: Casey CP. Anderson RL. J. Organomet. Chem.  1974,  73:  C28 
• 8 Aminocarbene complexes are about 10 pK _a units less acidic than the corresponding alkoxycarbene complexes: Bernasconi CF. Leyes AE. Ragains ML. Shi Y. Wang H. Wulff WD. J. Am. Chem. Soc.  1998,  120:  8632 
• 9a Semmelhack MF. Lee GR. Organometallics  1987,  6:  1839 
• 9b Reed AD. Hegedus LS. Organometallics  1997,  16:  2313 
• 10 Schwindt MA. Lejon T. Hegedus LS. Organometallics  1990,  9:  2814 
• 11 Xu YC. Wulff WD. J. Org. Chem.  1987,  52:  3263 
• 12a McDonald FE. Schultz CC. Chatterjee AK. Organometallics  1995,  14:  3628 
• 12b Aumann R. Hinterding P. Chem. Ber.  1990,  123:  2047 
• 12c Soderberg BC. Turbeville MJ. Organometallics  1991,  10:  3951 
• 13 Metal carbonyls perform similar reductions: Mitchell RH. Ward TR. Tetrahedron  2001,  57:  3689 
• 14 For a review of isobenzofurans, see: Friedrichsen W. Adv. Heterocycl. Chem.  1999,  73:  1 
• 15 Ghorai BK. Herndon JW. Organometallics  2003,  22:  3951 
• 17 Berkowitz DB. Choi S. Maeng JH. J. Org. Chem.  2000,  65:  847 
• 18 Meegalla SK. Rodrigo R. Synthesis  1989,  942 
• 19 For a review of phenanthridine synthesis, see: Balasubramanian M. Keay JG. In Comprehensive Heterocyclic Chemistry II   Vol. 5:  McKillop AE. Katritzky AR. Rees CW. Scriven EFV. Elsevier; Oxford: 1996.  p.245-300  
• 23 Armarego WLF. Sharma SC. J. Chem. Soc. C  1970,  1600 
• 24 This compound was prepared from Sonogashira coupling of hex-1-yne and 2-bromobenzaldehyde according to a literature procedure: Sakamoto T. Kondo Y. Miura N. Hayashi K. Yamanaka H. Heterocycles  1986,  24:  2311 
• 25This compound is known; however, the spectral data are inaccessible: (Laboratorios Made S.A., Spain) Span. Patent 74-423501;
• 25
• 26 This compound was prepared from Sonogashira coupling of trimethylsilylacetylene and 2-bromobenzaldehyde followed by desilylation according to a literature procedure: Acheson RM. Lee GCM. J. Chem. Soc., Perkin Trans. 1  1987,  2321 
• 27 This compound was prepared from Sonogashira coupling of hex-1-yne and 2-bromoacetophenone according to a literature procedure: Herndon JW. Zhang Y. Wang K. J. Organomet. Chem.  2001,  634:  1 
• 29 This compound was prepared from Sonogashira coupling of hex-1-yne and 2-iodobenzophenone according to a literature procedure: Tovar JD. Swager TM. J. Org. Chem.  1999,  64:  6499 
• 30 Frisch MJ. Trucks GW. Schlegel HB. Scuseria GE. Robb MA. Cheeseman JR. Zakrzewski VG. Montgomery JA. Stratmann RE. Burant JC. Dapprich S. Millam JM. Daniels AD. Kudin KN. Strain MC. Farkas O. Tomasi J. Barone V. Cossi M. Cammi R. Menucci B. Pomelli C. Adamo C. Clifford S. Ochterski J. Petersson GA. Ayala PY. Cui Q. Morokuma K. Malick DK. Rabuck AD. Raghavachari K. Foresman JB. Cioslowki J. Ortiz JV. Stefanov BB. Liu A. Liashenko A. Piskorz P. Komaromi I. Gomperts R. Martin RL. Fox DJ. Keith T. Al-Laham MA. Peng CY. Nanayakkara A. Gonzalez M. Callacombe M. Gill PMW. Johnson BG. Chen W. Wong MW. Andres JL. Head-Gordon M. Replogle ES. Pople JA. Gaussian03 Program   Gaussian Inc.; Pittsburgh PA: 1998. 

16

This compound was prepared from o-tolunitrile in a three-step sequence involving: (1) deprotonation with LDA followed by allylation with allyl bromide, (2) oxidation of the alkene to the aldehyde using OsO₄/NaIO₄, and (3) reaction of the aldehyde with 2-(dimethoxymethyl)phen-yllithium.

20

This is a variant of a literature procedure in reference 9b. This procedure is very reliable if one is careful to cut the potassium into small pieces and if the tetramethyl-ammonium acylate salt is prepared prior to the alkylation step. Otherwise we noted wide variances in the yields between different experimental runs.

21

Prepared from cis-1,2-cyclohexanedicarboxylic anhydride via amide formation (treatment with aqueous ammonia), followed by amide dehydration (Ac₂O), followed by acid chloride formation (oxalyl chloride).

22

Prepared from reaction of the acid chloride (ref. 21) with aqueous dimethylamine.

28

This compound was prepared from Sonogashira coupling of hex-1-yne and N,N-dimethyl-2-iodobenzamide according to a literature procedure. See reference 15.