Journal of the American Chemical Society
Article
where G is added at the outset. Saturation in [int2] within the
cycle itself rationalizes zero-order kinetics in [1]; zero-order
kinetics in [2] is observed because 2 enters the cycle after rate-
limiting formation of int3.
(b) Phua, P. H.; Mathew, S. P.; White, A. J. P.; de Vries, J. G.;
Blackmond, D. G.; Hii, K. K. Chem.Eur. J. 2007, 13, 4602.
(6) (a) Blackmond, D. G. J. Am. Chem. Soc. 1997, 119, 12934.
(
b) Blackmond, D. G. Acc. Chem. Res. 2000, 33, 402.
7) (a) von Kiedrowski, G. Angew. Chem., Int. Ed. Engl. 1986, 25,
rner, S.; Craig, S. L.; Lin, S.; Rudkevich, D.
(
9
32−935. (b) Chen, J.; Ko
̈
CONCLUSION
■
M.; Rebek, J., Jr. Proc. Natl. Acad. Sci., U.S.A. 2002, 99, 2593−2596.
(c) Sadownik, J. W.; Philp, D. Angew. Chem., Int. Ed. 2008, 51, 9965−
9970.
The unusual sigmoidal kinetic profile in the 1,3-dipolar
cycloaddition/condensation of nitro compounds first observed
by De Sarlo and Machetti is rationalized on the basis of detailed
kinetic analysis. The observation of near symmetry between the
sigmoidal substrate decay and product appearance curves
precludes an explanation based on the transient features of a
simple multistep stoichiometric reaction sequence. When the
autoinductive behavior is deconvoluted from the intrinsic
kinetics of the catalytic cycle, the distinct signature of the
sigmoidal reaction progress curves may be distinguished from
similar kinetic behavior with different mechanistic origins,
including true self-replicative autocatalysis, simple catalyst
activation, and product acceleration. In this case the sigmoidal
behavior is attributed to the dual role of nitroacetamide
substrate 1 as both a substrate and a catalyst precursor in its
own reaction. The use of reaction profiling is key to
distinguishing such kinetic features, which may lie behind
other seemingly simple transformations. Differentiating be-
tween the different origins of unusual kinetic behavior is critical
to its potential exploitation in reaction development and
optimization as well as for addressing fundamental mechanistic
questions including those related to kinetic models for prebiotic
metabolism.
(
8) (a) Blow, N. Nat. Methods 2007, 4, 869−875. (b) Saiki, R. K.;
Bugawan, T. L.; Horn, G. T.; Mullis, K. B.; Erlich, H. A. Nature 1986,
24, 163−166.
9) Yoon, H. J.; Mirkin, C. A. J. Am. Chem. Soc. 2008, 130, 11590−
1591.
10) (a) Soai, K.; Shibata, T.; Morioka, H.; Choji, K. Nature 1995,
78, 767. (b) Kawasaki, T.; Matsumura, Y.; Tsutsumi, T.; Suzuki, K.;
3
(
1
(
3
Ito, M.; Soai, K. Science 2009, 324, 492. (c) Soai, K.; Kawasaki, T.
Chem. Today 2009, 27, 3.
(11) (a) Blackmond, D. G.; McMillan, C. R.; Ramdeehul, S.; Schorm,
A.; Brown, J. M. J. Am. Chem. Soc. 2001, 123, 10103. (b) Buono, F. G.;
Blackmond, D. G. J. Am. Chem. Soc. 2003, 125, 8978. (c) Quaranta,
M.; Gehring, T.; Odell, B.; Brown, J. M.; Blackmond, D. G. J. Am.
Chem. Soc. 2010, 132, 15104.
(
12) (a) Watzky, M. A.; Finke, R. G. J. Am. Chem. Soc. 1997, 119,
0382−10400. (b) Besson, C.; Finney, E. E.; Finke, R. G. J. Am. Chem.
Soc. 2005, 127, 8179−8184.
13) For a review of the kinetics and mechanisms involved in
1
(
nanoparticle formation and growth, see: (a) Mondloch, J. E.; Bayram,
E.; Finke, R. G. J. Mol. Catal. A 2012, 355, 1−38. (b) Wang, F.;
Richards, V. N.; Shields, S. P.; Buhro, W. E. Chem. Mater. 2014, 26, 5−
21.
(14) Morris, A. M.; Watzky, M. A.; Agar, J. N.; Finke, R. G.
Biochemistry 2008, 47, 2413−2427.
(
(
15) Blackmond, D. G. Angew. Chem., Int. Ed. 2009, 48, 386−390.
16) (a) Cecchi, L.; De Sarlo, F.; Machetti, F. Tetrahedron Lett. 2005,
ASSOCIATED CONTENT
Supporting Information
■
*
S
4
2
6, 7877. (b) Cecchi, L.; De Sarlo, F.; Machetti, F. Eur. J. Org. Chem.
006, 4852. (c) Machetti, F.; Cecchi, L.; Trogu, E.; De Sarlo, F. Eur. J.
Experimental details, crystal structure information, and NMR
Org. Chem. 2007, 4352. (d) Guideri, L.; De Sarlo, F.; Machetti, F.
Chem.Eur. J. 2013, 19, 665. (e) De Sarlo, F.; Machetti, F. In Methods
and Apllications of Cycloaddition Reactions in Organic Synthesis, 1st ed.;
Nishiwaki, N., Ed.; John Wiley & Sons, Inc.: New York, 2014; pp
AUTHOR INFORMATION
2
05−222. (f) Biagiotti, G.; Cicchi, S.; De Sarlo, F.; Machetti, F. Eur. J.
Org. Chem. 2014, 7906−7915. (g) Trogu, E.; Vinattieri, C.; De Sarlo,
F.; Machetti, F. Chem.Eur. J. 2012, 18, 2081.
Notes
(17) Benson, S. W. J. Chem. Phys. 1956, 20, 1605−1612.
(
18) Hein, J. E.; Cao, B. H.; Viedma, C.; Kellogg, R. M.; Blackmond,
The authors declare no competing financial interest.
D. G. J. Am. Chem. Soc. 2012, 134, 12629.
19) (a) Spokes, G. N.; Benson, S. W. J. Am. Chem. Soc. 1967, 89,
030. (b) Khrapkovskii, G. M.; Shamov, A. G.; Nikolaeva, E. V.;
Chachkov, D. V. Russ. Chem. Rev. 2009, 78, 903.
20) Pascal, R.; Taillades, J.; Commeyras, A. Tetrahedron 1978, 34,
(
6
ACKNOWLEDGMENTS
Funding from NSF International Collaboration in Chemistry
CHE-1128395) and the Simons Foundation Collaboration on
■
(
(
the Origins of Life (SCOL award no. 287625) are gratefully
acknowledged. The authors thank Dr. Ryan Shenvi for fruitful
discussions.
2275.
(21) Matt, C.; Wagner, A.; Mioskowski, C. J. Org. Chem. 1997, 62,
234.
(22) Clayden, J.; Greeves, N.; Warren, S.; Wothers, P. Organic
Chemistry; Oxford University Press: Oxford, 2001; p 934.
REFERENCES
■
(
1) (a) Blackmond, D. G. Angew. Chem., Int. Ed. 2005, 44, 4302.
b) Mathew, J. S.; Klussmann, M.; Iwamura, H.; Valera, F.; Futran, A.;
(
Emanuelsson, E. A. C.; Blackmond, D. G. J. Org. Chem. 2006, 71, 4711.
(
2) Zuend, S. F.; Jacobsen, E. N. J. Am. Chem. Soc. 2009, 131, 15359.
(
3) Rosner, T.; Le Bars, J.; Pfaltz, A.; Blackmond, D. G. J. Am. Chem.
Soc. 2001, 123, 1848.
4) (a) Rosner, T.; Pfaltz, A.; Blackmond, D. G. J. Am. Chem. Soc.
001, 123, 4621. (b) Shekhar, S.; Ryberg, P.; Hartwig, J. F.; Mathew, J.
S.; Blackmond, D. G.; Strieter, E. R.; Buchwald, S. L. J. Am. Chem. Soc.
006, 128, 3584−3591. (c) Blackmond, D. G.; Schultz, T.; Mathew, J.
S.; Loew, C.; Rosner, T.; Pfaltz, A. Synlett 2006, 18, 3135.
5) (a) Mathew, S. P.; Klussmann, M.; Iwamura, H.; Wells, D. H., Jr.;
Armstrong, A.; Blackmond, D. G. Chem. Commun. 2006, 4291.
(
2
2
(
F
J. Am. Chem. Soc. XXXX, XXX, XXX−XXX