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COMMUNICATION
DOI: 10.1039/C4RA10105G
In all nineteen 1ꢀ(2H)ꢀisoquinolones based on 4 were synthesized in coordination of Ru with Nꢀatomꢀortho cyclometallationꢀinsertion of
66ꢀ88 % isolated yields. As is evident, the presence of a single an alkyne into the Ru–C bondꢀprotonationꢀreductive elimination
electronꢀdonating and ꢀwithdrawing groups in 1 at position 4 of the domino sequence. Further studies are in progress with application of
aromatic ring furnished products in >80 % isolated yield with other in situ generated DGs for the synhesis of heterocycles via de
minimal variations. However, introduction of two electronꢀ donating novo routes.
R. K. A., R. K., T. J. and R. M. are thankful to CSIR, and UGC
New Delhi, India for fellowships. The authors would like to thank
SAIF, CDRI, India for providing NMR data.
substituents in the aromatic ring at position 3 and 4 reduced the
isolated yield to 68ꢀ70%. Among symmetrical internal alkynes
replacement of R1 and R2 with aromatic ring bearing electronꢀ
donating groups produced corresponding 4 in relatively higher yield
(4ad) than aliphatic chain (4af, 4ae).
Notes and references
Employing unsymmetrical internal alkynes bearingꢀaliphatic/
aromatic and, aromatic/COOEt moieties as R1/R2 furnished 4ah and
4ag in good to moderate yields with high regioselectivity (Table 2).
aMedicinal & Process Chemistry Division, CSIRꢀCentral Drug Research
Institute, B.S. 10/1, Sector 10, Jankipuram Extension, Sitapur Road,
Lucknow, 226031, India.
Terminal alkyne failed to facilitate annulations. The versatility of bAcademy of Scientific and Innovative Research, New Delhi, 110001, India.
methodology was demonstrated by replacing benzoyl azides with cSophisticated Analytical Instrumental Facility, CSIRꢀCentral Drug Research
thiophene and indoleꢀbased acyl azides (1k-n). Treating with a Institute, Lucknowꢀ226031, India.
variety of internal alkynes furnished 8 examples of corresponding 4 † Electronic Supplementary Information (ESI) available: [details of any
in moderate to good isolated yields (Table 3).
supplementary information available should be included here]. See
Based on the literature reports,7c,7f,7g,10a,b,16 a plausible mechanism DOI: 10.1039/c000000x/
for the formation of 4aa is depicted in Scheme 3. The ruthenium
dimer precatalyst undergoes dissociation into the coordinatively
unsaturated monomer in solution, which exchanges ligand with
Cu(OAc)2·H2O to form an acetateꢀligated species. This metal upon
coordination with Nꢀatom of the iminophosphane 2a (derived from
1a) followed by ortho cyclometallation afforded a five membered
ruthenacycle I with the loss of acetic acid through an acetateꢀassisted
mechanism. This is then accompanied by the insertion of an alkyne
into the Ru–C bond to afford a seven membered ruthenacycle
intermediate II. Finally the protonation of II followed by reductive
elimination affords 4aa with the dissociation of triphenyl phosphine
by the in situ generated acetic acid16 and reduction of the ruthenium
from Ru(II) to Ru(0). Latter undergoes oxidation to regenerate the
catalytically active Ru(II) complex with the aid of copper oxidant.
1
For Directing group assisted C—H activation reviews, please see: (a)
L. Ackermann, Acc. Chem. Res. 2014, 47, 281; (b) D. A. Colby, R.
G. Bergman, and J. A. Ellman, Chem. Rev. 2010, 110, 624; (c) D. A.
Colby, A. S. Tsai, R. G. Bergman and J. A. Ellman, Acc. Chem. Res
.
2012, 45, 814; (d) K. M. Engle, T.ꢀS. Mei, M. Wasa and J.ꢀQ. Yu,
Acc. Chem. Res. 2012, 45, 788; (e), D. A. Colby, R. G. Bergman and
J. A. Ellman, Chem. Rev. 2010, 110, 624; (f) L. Ackermann, Chem.
Rev. 2011, 111, 1315; (g) T. Satoh and M. Miura, Chem. Eur. J
2010, 16, 11212. .
.
2
3
(a) S. Chen, J. Yu, Y. Jiang, F. Chen and J. Cheng, Org. Lett. 2013,
15, 4754; (b) J. Luo, S. Preciado and I. Larrosa, J. Am. Chem. Soc
2014, 136, 4109.
.
(a) J. R. Lewis, Nat. Prod. Rep. 1994, 11, 329; (b) M. C. Gonza´lez,
M. C. ZafraꢀPolo, M. A. Blázquez, A. Serrano and D. Cortes, J. Nat.
Prod. 1997, 60, 108; (c) C.ꢀY. Chen, F.ꢀR. Chang, W.ꢀB. Pan and Y.ꢀ
C. Wu, Phytochemistry. 2001, 56, 753; (d) Z. Zhang, S. Li, S. Zhang,
C. Liang, D. Gorenstein and R. S. Beasley, Planta Med. 2004, 70
,
1216.
4
(a) T. Hudlicky, U. Rinner, D. Gonzalez, H. Akgun, S. Schilling, P.
Siengalewicz, T. A. Martinot and G. R. Pettit, J. Org. Chem. 2002,
67, 8726; (b) V. A. Glushkov and Y. V. Shklyaev, Chem. Heterocycl.
Compd. 2001, 37, 663. (c) G. R. Pettit, Y. H. Meng, D. L. Herald, K.
A. N. Graham, R. K. Pettit and D. L. Doubek, J. Nat. Prod. 2003, 66
,
1065.
5
6
(a) A. Saeed and Z. Ashraf, Pharm. Chem. J. 2008, 42, 277; (b) W.ꢀJ.
Cho, M. J. Park, B. H. Chuang and C. O. Lee, Bioorg. Med. Chem.
Lett. 1998, 8, 41.
(a) H. T. M. Van, D. B. Khadka, S. H. Yang, T. N. Le, S. H. Cho, C.
Zhao, I.ꢀS. Lee, Y. Kwonb, K.ꢀT. Lee, Y.ꢀC. Kim and W.ꢀJ. Cho,
Bioorg. Med. Chem. 2011, 19, 5311; (b) T. Bosanac, E. R. Hickey, J.
Ginn, M. Kashem, S. Kerr, S. Kugler, X. Li, A. Olague, S. Schlyer
and E. R. R. Young, Bioorg. Med. Chem. Lett. 2010, 20, 3746.
Scheme 3. A plausible mechanism for the formation of 4aa via
iminophosphorane.
In summary we have described a Ruꢀcatalyzed ortho C—H
activation and intramolecular C—N bond formation via in situ
generated iminophosphanes as a directing group. The synthetic
protocol involves one pot condensation of acyl azides with internal
alkynes leading to straightforward and efficient synthesis of a variety
of annulated pyridinꢀ2(1H)ꢀones. The salient feature of the reaction
in DCE involves in situ generation of iminophosphoraneꢀ
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(a) N. Guimond, C. Gouliaras and K. Fagnou, J. Am. Chem. Soc.
2010, 132, 6908; (b) N. Guimond, S. I. Gorelsky, K. Fagnou, J. Am.
Chem. Soc. 2011, 133, 6449; (c) B. Li, H. Feng, S. Xu and Wang, B.
Chem. Eur. J. 2011, 17, 12573; (d) X. Xu, Y. Liu and C.ꢀM. Park,
Angew. Chem. Int. Ed. 2012, 51, 9372; (e) F. W. Patureau and F.
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