A meta-selective copper-catalyzed C-H bond arylation

Article abstract of DOI:10.1126/science.1169975

For over a century, chemical transformations of benzene derivatives have been guided by the high selectivity for electrophilic attack at the ortho/para positions in electron-rich substrates and at the meta position in electron-deficient molecules. We have

Full text of DOI:10.1126/science.1169975

REPORTS
11. R. A. Potyrailo, W. G. Morris, Anal. Chem. 79, 45 (2007).
12. M. Hosokawa, K. Nogi, M. Naito, T. Yokoyama,
Nanoparticle Technology Handbook (Elsevier, Oxford,
ed. 1, 2007).
13. T. H. J. van Osch, J. Perelaer, A. W. M. de Laat,
U. S. Schubert, Adv. Mater. 20, 343 (2008).
14. J. E. Smay, J. Cesarano III, J. A. Lewis, Langmuir 18, 5429
(2002).
15. Q. Li, J. A. Lewis, Adv. Mater. 15, 1639 (2003).
16. Y. Sun, Y. Xia, Science 298, 2176 (2002).
17. B. Wiley, Y. Sun, Y. Xia, Acc. Chem. Res. 40, 1067
(2007).
26. G. G. Harman, Wire Bonding in Microelectronics:
the silver nanoparticle concentration, size, and
distribution, we have produced inks with high
solids loading (≥70 wt %) that are ideally suited
for direct-write assembly. We have shown that
self-supporting microelectrodes in either planar
or 3D forms of arbitrary complexity can be pat-
terned on a wide variety of substrates. Using
this technique, we have further demonstrated the
feasibility of wire bonding to fragile devices and
patterning complex interconnects for solar cell
and LED arrays.
Process, Reliability, and Yield (McGraw-Hill Professional,
New York, 1997).
27. J.-H. Ahn et al., Science 314, 1754 (2006).
28. S. Ashley, Sci. Am. 299, 32 (2008).
29. This material is based on work supported by the U.S.
Department of Energy, Materials Sciences and Engineering
Division under award no. DEFG-02-07ER46471, through
the Frederick Seitz Materials Research Laboratory (FSMRL) at
the University of Illinois. The authors gratefully acknowledge
use of the FSMRL Central Facilities, including Center for
Microanalysis of Materials. B.Y.A. thanks the Korean Research
Foundation for the postdoctoral fellowship. We also thank
C. Hansen, M. Xu, R. Shepherd, J. Bukowski, J. Carroll III, and
J. Yoshikawa for useful discussions. J.A.L., B.Y.A., and E.B.D.
submitted a U.S. patent application on this work entitled
“Metal Nanoparticle Inks” on 3 October 2008.
18. M. Yamamoto, Y. Kashiwagi, M. Nakamoto, Langmuir 22,
8581 (2006).
19. A. Pyatenko, M. Yamaguchi, M. Suzuki, J. Phys. Chem. C
111, 7910 (2007).
References and Notes
20. B.-H. Ryu et al., Colloids Surf. A Physicochem. Eng. Asp.
270–271, 345 (2005).
1. D. B. Chrisey, Science 289, 879 (2000).
2. H. Sirringhaus et al., Science 290, 2123 (2000).
3. S. R. Forrest, Nature 428, 911 (2004).
4. Y. Sun, J. A. Rogers, Adv. Mater. 19, 1897 (2007).
5. E. Menard et al., Chem. Rev. 107, 1117 (2007).
6. M. C. LeMieux et al., Science 321, 101 (2008).
7. Q. Cao et al., Nature 454, 495 (2008).
8. J. Yoon et al., Nat. Mater. 7, 907 (2008).
9. J. A. Rogers et al., Proc. Natl. Acad. Sci. U.S.A. 98, 4835
(2001).
Supporting Online Material
www.sciencemag.org/cgi/content/full/1168375/DC1
Materials and Methods
Figs. S1 to S9
References
21. Materials and methods are available as supporting
material on Science Online.
22. M. Dobbelin et al., Chem. Mater. 19, 2147 (2007).
23. J. Ouyang et al., Polymer 45, 8443 (2004).
24. T. Li, Z. Huang, Z. Suo, S. P. Lacour, S. Wagner, Appl.
Phys. Lett. 85, 3435 (2004).
11 November 2008; accepted 27 January 2009
Published online 12 February 2009;
10.1126/science.1168375
25. D.-Y. Khang, H. Jiang, Y. Huang, J. A. Rogers, Science
311, 208 (2006); published online 14 December 2005
(10.1126/science.1121401).
10. V. Subramanian et al., Proc. IEEE 93, 1330 (2005).
Include this information when citing this paper.
nistic pathways most commonly form the ortho-
substitution product, and as a result there is a paucity
of methods for metal-catalyzed C–H bond activa-
tion at the meta position of a substituted benzene
ring (27, 28).
Here we describe the development of a re-
activity concept for a metal-catalyzed aromatic
C–H bond functionalization strategy that selec-
tively generates the elusive meta isomer. The
outcome is not predicted by the conventional
rules associated with electronic factors, directing
groups, or steric effects, and provides direct access
to the meta isomer on highly versatile electron-
rich aromatic structures. The process is simple,
proceeds under mild conditions, uses inexpensive
A Meta-Selective Copper-Catalyzed
C–H Bond Arylation
Robert J. Phipps and Matthew J. Gaunt*
For over a century, chemical transformations of benzene derivatives have been guided by the
high selectivity for electrophilic attack at the ortho/para positions in electron-rich substrates and
at the meta position in electron-deficient molecules. We have developed a copper-catalyzed
arylation reaction that, in contrast, selectively substitutes phenyl electrophiles at the aromatic
carbon–hydrogen sites meta to an amido substituent. This previously elusive class of
transformation is applicable to a broad range of aromatic compounds.
romatic organic compounds are ubiqui- Furthermore, in complex systems, where there copper catalysts, and forms valuable products that
tous in modern society as medicines and may be more than one electronic or sterically would be difficult to synthesize by other methods
functionalized materials (1). These mol- active substituent, the competition between these (Fig. 1B). Furthermore, the reactivity and selec-
A
ecules comprise cyclic aryl cores with an often directing groups may lead to mixtures of products. tivity of this process should be compatible with
complex array of substituents on the ring car- Although there have been some reports that other arene and C–H bond transformations and
bons, which in many cases are most straight- indirectly address these problems (4–7), circum- will streamline synthetic strategy for the assembly
forwardly appended by electrophilic substitution venting the inherent ortho/para-selectivity of of medicines, natural products, and industrially
(2). Ever since the pioneering work of Friedel electron-rich aromatic systems to generate the relevant aromatic molecules.
and Crafts (3), it has been widely established that meta product remains a largely elusive and unmet
electron-donating substituents direct incoming goal for chemical synthesis.
We previously identified a copper catalysis
system, based on electrophilic metalation, that
electrophiles to the ortho and para positions,
A central theme of our research has been the enables site-selective C–H bond arylation on the
whereas electron-withdrawing groups steer to the development of methods to obviate reliance on indole skeleton (Fig. 2A) (10). We speculated
meta position (Fig. 1A). This fundamental complex functional group manipulations through that a Cu(I) catalyst is oxidized to a Cu(III)-aryl
reactivity pattern facilitates a predictable outcome direct metal-catalyzed C–H bond transformations intermediate (29), a highly electrophilic d8-configured
in simple cases; however, a common problem (8, 9). A key aspect of this goal is the ability to metal species, that undergoes Friedel-Crafts–type
encountered in synthesis is how to access the control the site selectivity of these transforma- metalation and arylation at the C3 position of the
isomer that is not anticipated by these rules. tions under mild conditions; a challenge that is indole (Fig. 2B). We see C3 arylation when using
Solutions to this problem often require numerous further complicated by the ubiquitous nature of our copper catalyst, whereas an almost identical
functional group additions or manipulations in the C–H bond in organic molecules (10–15). process using Pd(II)-salts delivers the C2 isomer
order to tailor the directing electronic properties The three mechanisms that usually rationalize (30). Although the origin of this dichotomy re-
of the precursor to furnish the desired product. the majority of selective metal-catalyzed C–H bond mains unclear, it led us to speculate that use of
activation methods involve electrophilic aromatic our copper catalyst might enable us to reverse the
substitution with electron-rich, p-nucleophilic arenes established selectivity of other electrophilic Pd(II)-
Department of Chemistry, University of Cambridge, Lensfield
(16), concerted metalation-deprotonation with sim- catalyzed transformations. For example, many Pd(II)-
ple and electron-deficient benzenes (17–19), and catalyzed reactions are ortho-selective and have
directed cyclometalation (20–26). These mecha- been routinely developed by virtue of the coordinat-
Road, Cambridge CB2 1EW, UK.
*To whom correspondence should be addressed. E-mail:
mjg32@cam.ac.uk
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REPORTS
A Conventional electrophilic aromatic substitution
X
X
X
H
X
R
H
H
R
H
H
R
H
H
electrophilic aromatic
substitution
H
H
ortho directing
if X = directing group if X = electron withdrawing if X = electron donating group
eg NHAc eg NMe2
meta directing
para directing
group, eg NO2
B Meta-selective catalytic C–H bond arylation
EDG
EDG
H
H
meta-selective Cu(II)-catalyzed
C–H bond arylation
H
Fig. 1. (A) Conventional reactivity trends in electrophilic aromatic substitution. (B) Meta-selective catalytic C–H bond arylation. EDG, electron-donating
group; Me, methyl; Ac, acetyl.
ing effect of directing groups (20–26). We reasoned
Encouraged by these initial results, we next ad- stituent (SO2Me, 2k), we observed exclusive aryla-
that a highly electrophilic Cu(III)-aryl species could dressed reaction optimization with 2-methylanilides tion at the meta position to the amide group, in line
react through a different pathway with molecules as our model system. We found that changing with our hypothesis. When the pivanilide was sub-
such as acetanilides, potentially leading to a posi- the nature of the acyl group had a large effect on stituted in the meta position, the C–H arylation af-
tional isomer not observed in conventional aromatic the yield of the reaction without compromising the forded the 1,3,5 arene isomer, again with arylation
substitution reactions (Fig. 2C). The acetanilides meta-selectivity (Table 1, entries 2 to 6). The reac- taking place in the meta position to the nitrogen
are an important class of aromatic molecule that tion works with carbamate and urea groups (Table 1, substituent (entries 2l-p). Although the yields are
already undergoes a plethora of transformations entries 3 and 4), although the conversions are a little lower than those of the corresponding ortho-
leading to ortho/para products (20). Furthermore, only moderate. However, benzamides and piv- substituted anilides, this is not the result of other
the acetamide group is a versatile motif that can be anilides (Table 1, entries 5 and 6) performed isomeric products but of a slower reaction rate that
readily transformed into a range of other function- much better in the reaction, producing good leads to incomplete conversion of the starting ma-
alities through conventional synthetic procedures.
yields of the desired biaryl products. In all cases, terial. Particularly noteworthy is the tolerance of
To test this hypothesis, we treated acetanilide arylation is the result of reaction at the meta halogen groups (2m and 2o), which remain unaf-
1a with Ph2IOTf (the arylating agent; Ph, phenyl; position to the amide, and no reaction occurs in fected during the reaction; these examples dem-
Tf, triflate) in the presence of 10 mole % Cu(OTf)2 the absence of the copper catalyst.
onstrate that the copper-catalyzed C–H arylation
(catalyst) in 1,2-dichloroethane solvent at 70°C Although we cannot be certain of the precise provides a complementary platform for further
(31). Arylation occurred at the meta position to mechanism of the reaction at this stage, a possible elaboration via conventional Pd(0)-catalyzed cross-
afford 2a, albeit in low isolated yield (Table 1, rationalization could involve the highly electro- coupling chemistry. The simple pivanilide system
entry 1); and in line with our blueprint, no philic Cu(III)-aryl species activating the aromatic forms the meta-diarylation product (2q). The aryla-
products arising from monoarylation at the ortho ring sufficiently to permit an anti–oxy-cupration tion process can also be extended to systems bear-
or para position were observed (determined by 1H of the carbonyl group of an acetamide across the ing a para substituent, and the arylation takes place
nuclear magnetic resonance analysis, <5%). Fur- 2,3 positions on the arene ring (Fig. 2D, step 1). in the sterically most demanding position, consist-
thermore, no arylation was observed with com- This dearomatizing transformation would place ent with our meta-directing hypothesis, to form
pounds that do not possess an amide group (31). the Cu(III)-aryl species at the meta position, and 1,3,4,5-tetrasubstituted anilides (2r). In these cases,
The same exclusive meta-selectivity was ob- rearomatizing deprotonation (step 2) followed by the symmetrical diarylation predominates; how-
served with 2-methylacetanilide 1b, to form the reductive elimination (step 3) would deliver the ever, it is possible to access the 1,3,4-trisubstituted
meta product 2b, in improved 43% yield. These meta product (33).
monoarylated system (2s) by controlling the stoi-
outcomes are in contrast to the similar Pd(II)-
Having identified a suitable amide moiety, we chiometry of the reaction.
catalyzed C–H arylation of acetanilide that deliv- explored the substrate scope (Fig. 3A). The
More complex (tri- or tetrasubstituted) anilide
ered the ortho-substituted product (32). Only the copper-catalyzed meta-arylation displays broad starting materials are also compatible in this re-
elegant iridium-catalyzed C–H borylation, de- substrate capacity and is tolerant of a range of action, leading to highly functionalized products
veloped independently by Smith-Maleczka and substituents in all positions of the aromatic ring (2t-u) in reasonable to good yields. A hexa-
Hartwig-Miyuara-Ishiyama, can achieve such selec- (34). For example, ortho-substituted pivanilides substituted arene (2v) can be synthesized in moder-
tivity in certain cases (27, 28). The C–H borylation readily produce the 1,2,5-trisubstituted arene sys- ate yield by this process, and versatile heterocyclic
reaction is mainly influenced by the steric effects tem, in which arylation has taken place in the meta motifs such as the indoline system (2w) can be
on the aromatic molecule and leads to function- position to the amido group regardless of the selectively arylated to form useful products that
alization at a position that is not adjacent to any electronic properties of the ortho substituent [2f to would be difficult to access by other methods.
other group. In cases such as 1b, however, the 2j (2f-j)]. Although electron-deficient substrates Moreover, the nature of the aryl coupling partner
borylation reaction would be expected to afford a suffer from poorer reactivity, it is notable that even can be varied in the reaction, thereby extending the
mixture of meta and para isomers.
in the presence of a competing meta-directing sub- utility of this process. A range of steric, electronic,
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REPORTS
(A) Copper-catalyzed C–H bond functionalization concept
Cu(I)X
Pd(II) is a d8 metal
– electrophilic
Cu(III) is a d8 metal
– more electrophilic
C
H
Ar
Ar
Ar
C
I
R
Cu(III)
X
R–I
(B) Complementary catalysis between Pd(II) and Cu(II)
Ph
Pd(II) catalysis (ref. 30)
Cu(II) catalysis (ref. 10)
Ph
N
N
H
N
H
Ph
I Ph BF4
Ph
I Ph BF4
H
complementary reactivity
C3 arylation
C2 arylation
(C) This study – meta-C–H arylation of acetanilides with Cu(II) catalysis
R
R
H
R
H
H
O
N
N
O
N
O
Pd(II) catalysis (ref. 32)
Cu(II) catalysis
Ph
Ph
I Ph PF6
Ph
I
Ph BF4
Ph
ortho-arylation
meta-arylation
complementary reactivity
(D) Proposed mechanistic hypothesis
R
H
R
R
R
H
H
H
H
step 1
step 2
step 3
N
O
H
N
O
N
O
N
O
cat. Cu(OTf)2
Ph2IOTf
Ph
Ph
Cu(III)
Cu(III)
Ph
TfO–
OTf
OTf
meta-C–H bond cupration via dearomatizing 'oxy-cupration'
Fig. 2. Design blueprint for meta-selective copper-catalyzed C–H bond arylation (A to D). Ar, general aryl group; Ph, phenyl; Tf, triflate; R, general hydrocarbon group.
Table 1. Optimization studies for meta-selective Cu(II)-catalyzed C–H bond arylation. DCE,
1,2-dichloroethane.
and functionally diverse aryl groups can be
transferred via the unsymmetrical iodonium salts
(35) in good yields (Fig. 3B). In these cases, the
large size of the mesityl group precludes its transfer
in the coupling step, facilitating the formation of a
range of functionalized biaryl products (10, 30).
The meta-selectivity of this arylating trans-
formation can be controllably overridden in certain
cases, providing further access to alternative iso-
meric products (Fig. 4). A 3-oxygenated pivanilide
derivative can be tuned through simple and
straightforward manipulation of the oxygen-
protecting group to afford either the 1,3,5- or
1,3,6-trisubstituted arene product. For example, a
moderately electron-withdrawing 3-OTs group
(Ts, tosylate) facilitates reaction in the meta po-
sition to the amide motif, in line with our model,
to afford the 1,3,5-functionalization pattern (2x).
However, if the more electron-donating 3-OMe
group is incorporated, then the arylation is steered
to the 6-position (ortho to the amido group and
para to the methoxy) to give 2y in good yield.
This controllable switch in regioselectivity is
Reaction optimization
R2
R2
H
H
N
O
N
O
10 mol% Cu(OTf)2
R1
R1
2 equiv. Ph2IOTf
DCE, 70˚C
Ph
1a (R1= H, R2 = Me)
1b (R1= Me, R2 = Me)
2a-f
R1
product
yield %
R2
entry
1
2
3
4
5
6
2a
2b
2c
2d
2e
2f
14
43
45
31
73
79
H
Me
Me
Me
Me
Me
Me
Me
OMe
NEt2
Ph
CMe3
www.sciencemag.org SCIENCE VOL 323 20 MARCH 2009
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REPORTS
indicative of potential versatility in this arylation catalyzed arylation process. The method is best with exquisite selectivity. In certain cases the
method. suited to more electron-donating substitutents meta-selectivity can be overridden by strongly
A broad range of substrates is compatible on the anilide ring, but still tolerates electron- electron-donating substituents that provide a fur-
with this operationally simple and mild copper- withdrawing groups, producing the meta isomer ther platform for exploring the reaction parameters.
A Substrate scope
CMe3
CMe3
O
H
H
N
O
N
10 mol% Cu(OTf)2
X
X
Ph2IX (X = OTf or BF4), DCE, 50-70˚C, 24 to 48 h
1
2f-w
CMe3
O
CMe3
O
CMe3
O
CMe3
O
CMe3
O
CMe3
O
H
H
H
H
H
H
N
Me
N
N
N
N
N
Me
MeO
Ph
F
MeO2S
Me
Ph
Ph
Ph
Ph
Ph
Ph
2f, 79%
CMe3
2g, 86%
CMe3
2h, 93%
CMe3
2i, 84%
CMe3
2j, 55%
CMe3
2k, 11%
CMe3
H
H
H
H
H
H
N
O
N
O
N
O
N
O
N
O
N
O
Me
Ph
Br
Ph
F
Ph
Cl
Br
Ph EtO2C
Ph
Ph
Ph
2l, 67%
2m, 65%
2n, 62%
2o, 61%
2p, 31%
2q, 66%
Me3C
CMe3
CMe3
CMe3
O
CMe3
CMe3
O
H
H
H
H
H
O
N
O
N
O
N
N
O
N
N
Me
Me
Me
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Me
Me
Me
2r, 83%
Me
Me
2t, 81%
2s, 51%
2u, 67%
2w, 77%
2v, 44%
B Scope of aryl group transfer
X
yield
CMe3
H
CMe3
82%
78%
49%
82%
60%
70%
72%
44%
3a 4-Me
3b 4-F
3c 4-I
H
10 mol% Cu(OTf)2
DCE, 70˚C, 24 to 48 h
N
O
N
O
Me
Me
3d 4-CO2Et
3e 4-NO2
3f 3-CF3
3g 3-Br
Mes
I Ar OTf
X
1f
3
3h 2-Me
Fig. 3. Scope of anilide (A) and arylating (B) groups in the Cu(II)-catalyzed C–H bond arylation reaction; Mes, 2,4,6-trimethylphenyl; Et, ethyl. For 2s,
two equivalents of pivanilide were used.
CMe3
O
CMe3
O
CMe3
H
H
H
N
N
N
O
10 mol% Cu(OTf)2
10 mol% Cu(OTf)2
Ph
4 equiv. Ph2IBF4
DCE, 70˚C, 48 h
64% yield
1.5 equiv. Ph2IOTf
DCE, 50˚C, 22 h
76% yield
TsO
Ph
RO
MeO
2x
2y
Fig. 4. Controlling the site selectivity of the C–H arylation reaction; Ts, tosylate.
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REPORTS
15. L.-C. Campeau, D. J. Schipper, K. Fagnou, J. Am. Chem.
Soc. 130, 3266 (2008).
site and arylation. However, we do not see any sign of
We anticipate that this general copper-catalyzed
meta-C–H bond functionalization reaction will
provide direct access to the elusive positional
isomers in aromatic chemistry and have a major
impact on the way that complex molecules, phar-
maceuticals, and functionalized materials are
synthesized.
ortho-arylation that may be expected through this
pathway. For example, see (42).
16. C. Jia, T. Kitamura, Y. Fujiwara, Acc. Chem. Res. 34, 633
(2001) and references therein.
34. The pivaloyl amide moiety in 2f can be cleaved to
the corresponding amine (95% yield) on treatment with
HCl-EtOH at 100°C (see supporting online material).
35. M. Bielawski, M. Zhu, B. Olofsson, Adv. Synth. Catal.
349, 2610 (2007).
17. M. Lafrance, K. Fagnou, J. Am. Chem. Soc. 128, 16496
(2006).
18. D. Garcia-Cuadrado, A. A. C. Braga, F. Maseras,
A. M. Echavarren, J. Am. Chem. Soc. 128, 1066 (2006).
19. D. L. Davies, S. M. A. Donald, S. A. Macgregor,
J. Am. Chem. Soc. 127, 13754 (2005).
36. B.-J. Li, S.-D. Yang, Z.-J. Shi, Synlett 2008, 949 (2008)
and references therein.
References and Notes
20. For an overview of C–H bond functionalization on
acetanilides, see (21, 36).
37. L. V. Desai, K. J. Stowers, M. S. Sanford, J. Am. Chem.
Soc. 130, 13285 (2008).
1. J. Hassan, M. Sevignon, C. Gozzi, E. Schulz, M. Lemaire,
Chem. Rev. 102, 1359 (2002).
21. G. Brasche, J. Garcia-Fortanet, S. L. Buchwald, Org. Lett.
10, 2207 (2008).
38. X. Chen, X.-S. Hao, C. E. Goodhue, J.-Q. Yu, J. Am. Chem.
Soc. 128, 6790 (2006).
2. G. A. Olah, Friedel-Crafts and Related Reactions
(Wiley, New York, 1963).
22. For an example of pyridine directed ortho–C–H arylation,
see (37).
39. D.-H. Wang, T.-S. Mei, J.-Q. Yu, J. Am. Chem. Soc. 130,
3. C. Friedel, J. M. Crafts, Comptes Rendus 84, 1392
(1877).
14082 (2008).
23. For Cu(II)-catalyzed, pyridine-directed, C–H bond
functionalization, see (38).
40. R. K. Thalji, J. A. Ellman, R. G. Bergman, J. Am. Chem.
Soc. 126, 7172 (2004).
4. C. J. Rohbogner, G. C. Clososki, P. Knochel, Angew. Chem.
Int. Ed. 47, 1503 (2008).
24. For a recent example of carboxylate directed
ortho–C–H bond arylation, see (39).
41. S. Murai et al., Nature 366, 529 (1993).
42. G. Evindar, R. A. Batey, J. Org. Chem. 71, 1802 (2006).
43. We gratefully acknowledge the Biotechnology and
Biological Sciences Research Council and
5. J. P. Flemming, M. B. Berry, J. M. Brown, Org. Biomol.
Chem. 6, 1215 (2008).
25. For imine-directed C–H bond functionalization, see (40).
26. For ketone-directed C–H bond functionalization, see (41).
27. J.-Y. Cho, M. K. Tse, D. Holmes, R. E. Maleczka Jr.,
M. R. Smith III, Science 295, 305 (2002).
28. J. M. Murphy, X. Liao, J. F. Hartwig, J. Am. Chem. Soc.
129, 15434 (2007) and references therein.
29. D. H. R. Barton, J. P. Finet, J. Khamsi, Tetrahedron Lett.
28, 887 (1987).
6. R. E. Mulvey, F. Mongin, M. Uchiyama, Y. Kondo,
Angew. Chem. Int. Ed. 46, 3802 (2007).
7. V. Snieckus, Chem. Rev. 90, 879 (1990).
8. D. Alberico, M. E. Scott, M. Lautens, Chem. Rev. 107, 174
(2007).
GlaxoSmithKline for an Industrial Case Award to R.J.P.,
the Royal Society for a University Research Fellowship to
M.J.G., and Philip and Patricia Brown for a Next
Generation Fellowship to M.J.G. We also thank S. Peace
(GSK Medicines Research Center, UK) for useful
discussion.
9. K. Godula, D. Sames, Science 312, 67 (2006).
10. R. J. Phipps, N. P. Grimster, M. J. Gaunt, J. Am. Chem.
Soc. 130, 8172 (2008) and references therein.
11. N. P. Grimster, C. Gauntlett, C. R. A. Godfrey, M. J. Gaunt,
Angew. Chem. Int. Ed. 44, 3125 (2005).
12. E. M. Beck, N. P. Grimster, R. Hatley, M. J. Gaunt, J. Am.
Chem. Soc. 128, 2528 (2006).
30. N. R. Deprez, D. Kalyani, A. Krause, M. S. Sanford, J. Am.
Chem. Soc. 128, 4972 (2006).
Supporting Online Material
www.sciencemag.org/cgi/content/full/323/5921/1593/DC1
Materials and Methods
References
Spectral Data
31. Materials and methods are available as supporting
material on Science Online.
32. O. Daugulis, V. G. Zaitsev, Angew. Chem. Int. Ed. 44,
4046 (2005).
13. D. R. Stuart, K. Fagnou, Science 316, 1172 (2007).
14. D. R. Stuart, E. Villemure, K. Fagnou, J. Am. Chem. Soc.
129, 12072 (2007).
33. We cannot rule out coordination of the Cu(III) species at
the ortho position, followed by a migration to the meta
18 December 2008; accepted 2 February 2009
10.1126/science.1169975
scattered through at least eight Cambrian taxa.
This realization clarifies the systematics and
complex morphology of Burgess Shale anom-
alocaridids, revealing that previous reconstruc-
tions of Anomalocaris and Laggania have been
partially misled by the inclusion of Hurdia ma-
terial. For clarity, generic names previously ap-
plied to anomalocaridid body parts are referred
to as follows: “Hurdia” (7) is referred to as the
H-element, “Proboscicaris” (8) as the P-element
(with both together as the frontal carapace),
“Peytoia” (2) as the mouthpart, and “append-
The Burgess Shale Anomalocaridid
Hurdia and Its Significance for Early
Euarthropod Evolution
Allison C. Daley,1* Graham E. Budd,1 Jean-Bernard Caron,2
Gregory D. Edgecombe,3 Desmond Collins4
As the largest predators of the Cambrian seas, the anomalocaridids had an important impact
in structuring the first complex marine animal communities, but many aspects of anomalocaridid age F” (3–5) as frontal appendage.
morphology, diversity, ecology, and affinity remain unclear owing to a paucity of specimens.
Here we describe the anomalocaridid Hurdia, based on several hundred specimens from the
Burgess Shale in Canada. Hurdia possesses a general body architecture similar to those of
Anomalocaris and Laggania, including the presence of exceptionally well-preserved gills, but
differs from those anomalocaridids by possessing a prominent anterior carapace structure.
These features amplify and clarify the diversity of known anomalocaridid morphology and
provide insight into the origins of important arthropod features, such as the head shield and
respiratory exites.
Systemic paleontology. Stem Euarthropoda,
Class Dinocarida, Order Radiodonta, Genus Hurdia
Walcott, 1912. Synonymy and taphonomy. See
supporting online material (SOM) text. Type
species. Hurdia victoria Walcott, 1912. Revised
diagnosis. Anomalocaridid with body divided
into two components of subequal length: ante-
rior with a nonmineralized reticulated frontal
carapace and posterior consisting of a trunk with
ike other anomalocaridids (1), Hurdia has These genera possess stalked eyes, frontal append- seven to nine lightly cuticularized segments. The
a complex history. The mouthparts (2), ages, a circular toothed mouth structure, and a frontal carapace includes a triangular H-element
frontal appendages (3–5), body (6), and body bearing gills in association with lateral attached dorsally and a pair of lateral P-elements.
L
frontal carapaces (7, 8) were all first described flaps. Later, Collins (10, 11) informally recog-
in isolation as separate animals with disparate nized that a third undescribed anomalocaridid
affinities, including medusoids, holothurians, exhibits all these features, as well as a prominent
and various arthropods (1). When research in anterior carapace composed of a triangular ele-
the 1980s revealed that many of these taxa were ment, the Hurdia carapace (7), together with the
in fact different parts of the same animal, two purported phyllopod carapace Proboscicaris (8).
1Department of Earth Sciences, Palaeobiology, Uppsala Uni-
versity, Villavägen 16, Uppsala SE-752 36, Sweden. 2Depart-
ment of Natural History, Royal Ontario Museum, 100 Queen’s
Park, Toronto M5S 2C6, Canada. 3Department of Palaeontol-
ogy, Natural History Museum, Cromwell Road, London SW7
5BD, UK. 4437 Roncesvalles Avenue, Toronto M6R 3B9,
Canada.
anomalocaridid genera were defined (9), and
Access to important new material at the Royal
several specimens here identified as Hurdia Ontario Museum and restudy of older collec-
*To whom correspondence should be addressed. E-mail:
were assigned to either Anomalocaris or Laggania. tions (12) identified parts of the Hurdia animal allison.daley@geo.uu.se
www.sciencemag.org SCIENCE VOL 323 20 MARCH 2009
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