Iron-catalyzed [2π + 2π] cycloaddition of α,ω-dienes: The importance of redox-active supporting ligands

Article abstract of DOI:10.1021/ja064711u

The bis(imino)pyridine iron bis(dinitrogen) complex, (ⁱPrPDI)Fe(N₂)₂ (ⁱPrPDI = 2,6-(2,6-ⁱPr₂C₆H₃NCR)₂C₅H₃N), serves as an efficient precursor for the catalytic [2π + 2π] cycloaddition of α,ω-dienes to yield the corresponding bicycles. For amine substrates, the rate of catalytic turnover increases with the size of the nitrogen substituents, demonstrating competing heterocycle coordination and product inhibition. In one case, a bis(imino)pyridine iron azobicycloheptane product was characterized by X-ray diffraction. Preliminary mechanistic studies highlight the importance of the redox activity of the bis(imino)pyridine ligand to maintain the ferrous oxidation state throughout the catalytic cycle. Copyright

Full text of DOI:10.1021/ja064711u

Published on Web 09/22/2006
Iron-Catalyzed [2π + 2π] Cycloaddition of r,ω-Dienes: The Importance of
Redox-Active Supporting Ligands
Marco W. Bouwkamp, Amanda C. Bowman, Emil Lobkovsky, and Paul J. Chirik*
Department of Chemistry and Chemical Biology, Baker Laboratory, Cornell UniVersity, Ithaca, New York 14850
Received July 3, 2006; E-mail: pc92@cornell.edu
The metal-catalyzed [2π + 2π] cycloaddition of olefins to form
cyclobutanes is an attractive transformation for the direct construc-
tion of strained four-membered rings.1 While thermally forbidden,2
photochemical methods,3 use of strained olefins, activated π-systems
(e.g., allenes), and transition metal reagents have all been employed
to circumvent the constraints of orbital symmetry.1 Examples of
metal catalyzed [2π + 2π] cycloadditions have broadened the scope
of this transformation to include styrene derivatives4 and the
conversion of bis(enones) into bicyclo[3.2.0] ring systems.5 Here
we describe the iron-catalyzed synthesis of a family of bicyclo-
[0.2.3]heptane derivatives via intramolecular [2π + 2π] cycload-
dition of the corresponding R,ω-dienes. A key feature of the
catalytic cycle is the redox activity of the supporting bis(imino)-
pyridine ligand.
Table 1. [2π + 2π] Cycloaddition of R,ω-Dienesa
time
conversion
(%)
TOF
∆
G
°
∆H
°
∆S°
1
E
(min)
(h-
)
(kcal/mol)
(kcal/mol)
(eu)
1
2
3
4
5
6
7
CH2
300
300
300
26
<5
300
92
0
0
90
>95
24
1.8
0
-9.4
-6.2
-11.4
-14.0
-18.3
-13.2 -12.6
-10.9 -15.8
-15.3 -12.7
-17.4 -11.3
SiMe2
NHb
0
N-Bn
N-tBu
NBoc
21c
>240d
-21.0
-18.6 -10.3
-19.1 -9.4
-9.5
0.5 -15.5
4 -16.3
C(CO2Et)2 141
>95
Recently our laboratory described the synthesis of the bis(imino)-
pyridine iron bis(dinitrogen) complexes, (iPrPDI)Fe(N2)2 (iPrPDI
) 2,6-(2,6-iPr2C6H3NCR)2C5H3N; R ) Me, 1-(N2)2, R ) Ph,
2-(N2)2), that serve as efficient precursors for the catalytic
hydrogenation of olefins, alkynes,6 and aryl azides.7 More detailed
computational, spectroscopic, and structural studies established a
two electron reduced bis(imino)pyridine ligand, suggesting Fe(II)
rather than Fe(0) as the active species.8 As part of our continuing
effort to expand the role of inexpensive and relatively nontoxic
iron catalysts in organic synthesis, the construction of small rings
via the cyclization of R,ω-dienes was explored.
Inspired by the work with group 3 transition metal and lanthanide
catalysts,9 the cyclization of 1,5-hexadiene was attempted. Stirring
the diolefin with 10 mol % of 1-(N2)2 under 0.5 atm of H2 yielded
a mixture of methylenecyclopentane as well as the hydrogenation
products, methylcyclopentane and n-hexane (see Supporting In-
formation). The selectivity of the catalytic reaction was improved
and formed only methylenecyclopentane when the iron dihydrogen
complex (iPrPDI)Fe(η2-H2) (1-(H2)) was employed as the precata-
lyst. Attempts to extend the scope of the catalytic cyclization to
1,6-heptadiene produced a different result. In this case, cyclization
with 10 mol % 1-(N2)2 with 0.5 atm H2 yielded n-heptane and a
new alkane, identified as the cis isomer of bicyclo[0.2.3]heptane,
arising from intramolecular [2π + 2π] cycloaddition of the two
terminal olefins (eq 1).
a Conditions: 0.5 mL of a 0.010 M C6D6 solution of 1-(N2)2, 10 equiv
of substrate, 23 °C. b Stoichiometric reaction (vide infra). c 90% conversion;
diminishes after 26 min owing to product inhibition (see text). d >95% in
<5 min.
1-(N2)2. The yields did not change when the reactions were
conducted in the dark, suggesting thermal processes.
The stereochemistry of the catalytic [2π + 2π] reactions was
also investigated with the cyclization of (Z,Z)-tBuN(CH2CHd
CHD)2. Exposure of the labeled substrate to 10 mol % of 1-(N2)2
produced no isotopic scrambling affording only one isotopomer of
the cyclized product (eq 2). The converse experiment with the (E,E)
diolefin yielded the complimentary isotopomer.
The iron catalyst is tolerant of amine and ester functional groups
as evidenced by facile cyclizations of diallyl-tert-butylamine and
diethyldiallylmalonate (entries 5 and 7, respectively). N-Boc and
benzyl-protected amines also undergo efficient conversion to the
corresponding bicycle. Also presented in Table 1 are the DFT-
computed thermodynamic values for each reaction; all of the [2π
+ 2π] cycloadditions to cis products (observed) are spontaneous.
Some substrates, such as E ) SiMe2 and those with internal olefins
(allyl-tert-butylcrotylamine or tertbutyldicrotylamine), were not
successfully cyclized even though the reaction is thermodynamically
favorable.
The observation of efficient R,ω-diene cycloaddition to yield
the corresponding bicycle prompted investigation into the scope
of the catalytic C-C bond-forming reaction. Table 1 reports a
family of diolefins that undergo [2π + 2π] cycloaddition at 23 °C
using 1-(N2)2 as the catalyst precursor. Typically the catalytic
reactions were conducted with 10 mol % of 1-(N2)2, and the
conversion was monitored by 1H NMR spectroscopy. Alternatively,
catalytic turnover was accomplished by in situ activation of air-
stable 1-Br2 with NaBEt3H, obviating the synthesis of sensitive
1
Monitoring the [2π + 2π] cyclization reactions by H NMR
spectroscopy provided insight into the relative rates of conversion
for the series of amine substrates. In the case where E ) NtBu, the
iron bis(dinitrogen) complex, 1-(N2)2 was recovered at the comple-
tion of catalysis. For E ) NBn, the bis(imino)pyridine iron
9
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J. AM. CHEM. SOC. 2006, 128, 13340-13341
10.1021/ja064711u CCC: $33.50 © 2006 American Chemical Society

C O M M U N I C A T I O N S
Figure 1. ORTEP representation of 1-(HNC6H10) (left) and 1-(C4H6) (right) at 30 % probability. Hydrogen atoms are omitted for clarity. Selected distances
(Å) are also included.
Scheme 1
benzylamine complex, 1-(BnNC6H10), was identified following
turnover. Diallyamine, the least hindered in the series, produced
only stoichiometric [2π + 2π] cyclization, cleanly affording
1-(HNC6H10) upon addition to 1-(N2)2 (eq 3). Liberation of free
azobicyclo[0.2.3]heptane was accomplished by exposure to 1 atm
of carbon monoxide. Thus, product inhibition dictates the rate of
catalytic turnover, where the less substituted and hence more
nucleophilic azabicycles coordinate more tightly and inhibit conver-
sion. It should also be noted that the most facile cycloadditions
were observed for the most thermodynamically favored cases,
consistent with the Thorpe-Ingold effect.10
dition that takes advantage of the unique electronic structure of
bis(imino)pyridine iron compounds.
Acknowledgment. We thank the Packard Foundation for finan-
cial support. P.J.C. is a Cottrell Scholar supported by the Research
Corporation and a Camille Dreyfus Teacher-Scholar. We also thank
Professor Barry Carpenter for assistance with the DFT calculations.
Supporting Information Available: Additional experimental,
computational, and crystallographic data. This material is available free
of charge via the Internet at http://pubs.acs.org.
Red brown 1-(HNC6H10) was characterized by X-ray diffraction
References
(Figure 1). Both the metrical parameters and NMR spectroscopic
data are analogous to the N,N-(dimethylamino)pyridine iron
compound, 1-DMAP,8a where computational, spectroscopic, and
structural data established an intermediate spin (SFe ) 1) ferrous
(1) (a) Lautens, M.; Klute, W.; Tam, W. Chem. ReV. 1996, 96, 49-62. (b)
For a more recent Ni example, see (b) Saito, S.; Hirayama, K.; Kabuto,
Yamamoto, Y. J. Am. Chem. Soc. 2000, 122, 10766.
(2) Woodward, R. B.; Hoffmann, R. Angew. Chem., Int. Ed. Engl. 1969, 8,
781.
(3) Crimmins, M. T. In ComprehensiVe Organic Synthesis; Trost, B. M.,
Fleming, I., Paquette, L. A., Eds.; Pergamon: Oxford, 1991; Vol. 5, p
123.
(4) Ohara, H.; Itoh, T.; Nakamura, M.; Nakamura, E. Chem. Lett. 2001, 7,
624.
(5) (a) Wang, L.-C.; Jang, H.-Y.; Roh, Y.; Lynch, V.; Schultz, A. J.; Wang,
X.; Krische, M. J. J. Am. Chem. Soc. 2002, 124, 9448. (b) Baik, T.-G.;
Luiz, A. L.; Wang, L.-C.; Krische, M. J. Am. Chem. Soc. 2001, 123, 6716.
(c) Yang, J.; Cauble, D. F.; Berro, A. J.; Bauld, N. L.; Krische, M. J. J.
Org. Chem. 2004, 69, 7979.
(6) (a) Bart, S. C.; Lobkovsky, E.; Chirik, P. J. J. Am. Chem. Soc. 2004, 126,
13794. (b) Archer, A. M.; Bouwkamp, M. W.; Cortez, M.-P.; Lobkovsky,
E.; Chirik, P. J. Organometallics 2006, 25, 4278.
(7) Bart, S. C.; Lobkovsky, E.; Bill, E.; Chirik, P. J. J. Am. Chem. Soc. 2006,
128, 5302.
(8) (a) Bart, S. C.; Chlopek, K.; Bill, E.; Bouwkamp, M. W.; Lobkovsky, E.;
Neese, F.; Wieghardt, K.; Chirik, P. J. J. Am. Chem. Soc., in press. (b) de
Bruin, B.; Bill, E.; Bothe, E.; Weyermu¨ller, T.; Wieghardt, K. Inorg. Chem.
2000, 39, 2936. (c) Scott, J.; Gambarotta, S.; Korobkov, I.; Knijnenburg,
Q.; de Bruin, B.; Budzelaar, P. H. M. J. Am. Chem. Soc. 2005, 127, 17204.
(9) (a) Molander, G. A.; Hoberg, J. O. J. Am. Chem. Soc. 1992, 114, 3123.
(b) Piers, W. E.; Shapiro, P. J.; Bunel, E. E.; Bercaw, J. E. Synlett 1990,
2, 74. (c) Trost, B. M.; Krische, M. J. Synlett 1998, 1.
(10) (a) Beesley, R. M.; Ingold, C. K.; Thorpe, J. F. J. Chem. Soc. 1915, 107,
1080. (b) Ingold, C. K. J. Chem. Soc. 1921, 119, 305. (c) Ingold, C. K.;
Sako S.; Thorpe, J. F. J. Chem. Soc. 1922, 120, 1117.
(11) (a) Norman, D. W.; Ferguson, M. J.; McDonald, R.; Stryker, J. M.
Organometallics 2006, 25, 2705. (b) Bachler, V.; Grevels, F.-W.; Kerpen,
K.; Olbrich, G.; Schaffner, K. Organometallics 2003, 22, 1696.
(12) Campora, J.; Palma, P.; Carmona, E. Coord. Chem. ReV. 1999, 193-
195, 207.
center complexed by a bis(imino)pyridine dianion, [iPrPDI]2-
.
To gain further insight into the mechanism of the cyclization
reaction and in particular, the nature of the R,ω-diene intermediate,
1-(N2)2 was treated with a diolefin unlikely to undergo intramo-
lecular [2π + 2π] cycloaddition. For this reason, 1,3-butadiene was
added to 1-(N2)2 and yielded a red, diamagnetic solid identified as
the iron-butadiene compound, 1-(C4H6). The solid-state structure
(Figure 1, right) reveals a rare example of trans-butadiene coordina-
tion11 in addition to a two electron reduced bis(imino)pyridine
chelate. These data support an Fe(II) complexed by [iPrPDI]2- rather
than an Fe(0) ion with a neutral chelate.8
The proposed mechanism (Scheme 1) for the catalytic [2π +
2π] cycloaddition involves initial substitution of the N2 ligands by
the diene. Based on the properties of 1-(C4H6), the oxidation states
of the iron are maintained as ferrous throughout the process.
Following C-C coupling to form the metallocycle, formal reductive
elimination yields the observed bicycle and regenerates the iron
diene complex. The redox activity of the [iPrPDI] ligand preserves
the ferrous oxidation state throughout the cycle and may prevent
complications from Fe(0) precipitation that are observed with other
(e.g., Ni) metallocycles.12
In summary, we have discovered an efficient method for the
synthesis of cyclobutanes via iron-catalyzed [2π + 2π] cycload-
JA064711U
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