Journal of the American Chemical Society
COMMUNICATION
Scheme 2. Representative Synthetic Applications of Diazo
Compound 2aa
’ REFERENCES
(1) (a) Regitz, M.; Maas, G. Diazo Compounds: Properties and
Synthesis; Academic Press: London, 1986; pp 65ꢀ198. (b) Padwa, A.;
Weingarten, M. D. Chem. Rev. 1996, 96, 223.(c) Doyle, M. P.;
McKervey, M. A.; Ye, T. Modern Catalytic Methods for Organic Synthesis
with Diazo Compounds; Wiley: New York, 1998. (d) Davies, H. M. L.;
Beckwith, R. E. J. Chem. Rev. 2003, 103, 2861. (e) Zhang, Z.; Wang, J.
Tetrahedron 2008, 64, 6577.
(2) For a recent review on the synthesis of diazo compounds, see:
(a) Maas, G. Angew. Chem., Int. Ed. 2009, 48, 8186. For selected reports
on remote functionalized diazo compounds, see: (b) Xu, X.; Hu, W.-H.;
Doyle, M. P. Angew. Chem., Int. Ed. 2011, 50, 6392. (c) Zhou, L.; Doyle,
M. P. Org. Lett. 2010, 12, 796. (d) Yu, L.; Zhang, Y.; Jee, N.; Doyle, M. P.
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Lett. 2005, 7, 5171. (f) Deng, G.; Tian, X.; Qu, Z.; Wang, J. Angew. Chem.,
Int. Ed. 2002, 41, 2773. (g) Liao, M.; Dong, S.; Deng, G.; Wang, J.
Tetrahedron Lett. 2006, 47, 4537. (h) Zhao, Y.; Wang, J. Synlett
2005, 28886. (i) Dong, C.; Mo, F.; Wang, J. J. Org. Chem. 2008, 73,
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(k) Padwa, A.; Zhang, Z. J.; Zhi, L. J. Org. Chem. 2000, 65, 5223.
(3) Trost, B. M.; Breder, A.; O'Keefe, B. M.; Rao, M.; Franz, A. W.
J. Am. Chem. Soc. 2011, 133, 4766.
(4) Padwa, A.; Kulkarni, Y. S.; Zhang, Z. J. Org. Chem. 1990, 55,
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(5) Barluenga, J.; Riesgo, L.; Lꢀopez, L. A.; Rubio, E.; Tomꢀas, M.
Angew. Chem., Int. Ed. 2009, 48, 7569.
(6) Control experiments demonstrated that no reaction takes place
in the absence of the copper catalyst. Screening of other catalysts led to
much poorer results. In particular, various copper(I) catalysts afforded
complex mixtures of products.
(7) The use of alcohols as the solvent in reactions involving
iodosylbenzene is a common practice. The high solubility of this reagent
in these solvents is ascribed to its solvolysis that forms iodobenzene
dialkoxide, PhI(OR)2. See: Schardt, B. C.; Hill, C. L. Inorg. Chem. 1983,
22, 1563.
(8) Diazomethylphosphonate esters are precursors of cyclopropyl-
phosphonates, a class of compounds with potential biological activity:
Davies, H. M. L.; Lee, G. H. Org. Lett. 2004, 6, 2117.
(9) The exact nature of the intermediates involved in the reaction
of iodosylbenzene and copper(II) ions is unclear. See, for example:
Franklin, C. C.; VanAtta, R. B.; Tai, A. F.; Valentine, J. S. J. Am. Chem.
Soc. 1984, 106, 814.
(10) A control experiment (2a, Cu(OTf)2, 5 mol%, MeOH, rt, 2 h)
confirmed that ketals 4 are not formed from the corresponding
ketones 2.
(11) When a more nucleophilic substrate, like the silyloxy-substi-
tuted vinyl diazoacetate 1m (R1 = OSiMe2tBu), was employed the
reaction followed a different pathway affording the expected dimeriza-
tion product 8. For the dimerization of simple silylenol ethers, see:
Zhdankin, V. V.; Mullikin, M.; Tykwinski, R.; Berglund, B.; Caple, R.;
Zefirov, N. S.; Koz'min, A. S. J. Org. Chem. 1989, 54, 2605.
a The reported yields are those of the isolated products after purification
by column chromatography.
isopropanol led efficiently to the γ-oxo-α-isopropoxypentanoate
ester 6.16 Interestingly, the metal-free arylation allowed the
selective creation of a CꢀC bond at the diazo function giving
rise to 7 in a synthetically useful yield.17
In summary, we have developed a convenient Cu(II)-cata-
lyzed synthesis of novel β-oxodiazo compounds and their ketal-
protected derivatives from vinyldiazo compounds and iodosyl-
benzene via an unprecedented oxidation/1,2-shift of the diazoa-
cetate function. The easy access to this new building block
featuring two significant β-functionalities (carbonyl and diazo
groups) will likely be useful in designing new synthetic meth-
odologies. Thus, fundamental diazo transformations (β-H elim-
ination, cyclopropanation, OꢀH insertion, reductive arylation)
work well allowing for the regioselective preparation of an array
of 1,4-dicarbonyl derivatives with hetero- and carbosubstitution
at a specific α-position.
’ ASSOCIATED CONTENT
S
Supporting Information. Full experimental details and
b
spectral data for all the products. This material is available free of
’ AUTHOR INFORMATION
Corresponding Author
barluenga@uniovi.es; lalg@uniovi.es
(12) This methodology would be a practical experimental protocol
for the indirect, chemoselective substitution reactions of unsymmetrical
1,4-dicarbonyl systems. For selected recent regioselective syntheses of
substituted γ-keto esters, see: (a) Gururaja, G. N.; Mobin, S. M.;
Namboothiri, I. N. N. Eur. J. Org. Chem. 2011, 2048. (b) Wang, W.;
Xu, B.; Hammond, G. B. J. Org. Chem. 2009, 74, 1640. (c) Zhao, W.-J.;
Yan, M.; Huang, D.; Ji, S.-J. Tetrahedron 2005, 61, 5585.
(13) We have experienced that thermal induced elimination
(toluene, 110 °C) produces the Z-alkene as the major stereoisomer
(Z/E = 4:1). For the Z-selective Rh(II)-catalyzed elimination in
alkyldiazoacetates, see: Taber, D. F.; Herr, R. J.; Pack, S. K.; Geremia,
’ ACKNOWLEDGMENT
This paper is dedicated to Professor Gerhard Erker on the
occasion of his 65th birthday. We are grateful to the Ministerio de
Ciencia e Innovaciꢀon of Spain (MICINN) (Grant CTQ2010-
20517-C02-01). G.L. and L.R. thank the MICINN and European
Union (Fondo Social Europeo) for predoctoral fellowships.
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dx.doi.org/10.1021/ja208965b |J. Am. Chem. Soc. 2011, 133, 18138–18141