Article pubs.acs.org/Organometallics
Mechanism of Catalytic Nitrene Transfer Using Iron(I)−Isocyanide Complexes Ryan E. Cowley, Matthew R. Golder, Nathan A. Eckert, Malik H. Al-Afyouni, and Patrick L. Holland*,† Department of Chemistry, University of Rochester, Rochester, New York 14627, United States S Supporting Information *
ABSTRACT: Low-spin iron(I) complexes supported by bulky βdiketiminate ligands catalyze the formation of unsymmetric carbodiimides (RNCNR′, R ≠ R′) from isocyanides and organoazides. In situ EPR studies indicate that the catalytic resting state in these reactions is the tris(isocyanide)iron(I) complex LFe(CNR)3, and kinetic experiments show that the reaction is inverse second-order in isocyanide concentration, suggesting that two isocyanide molecules dissociate prior to the rate-determining step. An unusual iron−carbodiimide complex can be isolated independently, and facile displacement of the coordinated carbodiimide by both isocyanide and N2 demonstrate that product release is not kinetically limiting during catalysis. These experimental data fit a coherent mechanism for the catalytic C−N coupling reaction, and the implications for catalytic nitrene transfer are discussed.
■
INTRODUCTION Carbodiimides (RNCNR′) are a versatile class of molecules1,2 used for peptide cross-linkers,3,4 carboxylic acid activators in polypeptide synthesis,5,6 polymers and polymer precursors,7 and building blocks for natural product synthesis.8 Unsymmetric carbodiimides (where R ≠ R′) are precursors of unsymmetric amidinates9 and helical polyguanidine polymers.10,11 Several organic and organometallic catalysts have been identified that produce carbodiimides through isocyanate (RNCO) coupling;12−14 however this approach is most useful for preparation of symmetric carbodiimides since coupling of different isocyanates inevitably produces a mixture of heterocoupled and homocoupled carbodiimide products. The addition of azides (RN3) to isocyanides (CNR′) with loss of N2 to afford a carbodiimide is a known stoichiometric reaction of metal−isocyanide complexes that typically requires high temperatures.15−24 An early report demonstrated that Fe(CO)5 catalyzed carbodiimide formation from CNR and RN3 in 48−60% yield, but only at 90 °C with excess isocyanide substrate.25 It was not until recently that homogeneous catalysts were discovered that afford unsymmetric carbodiimides at lower temperatures and in higher yields (Scheme 1). In each case, a metal−imido complex was implicated as the reactive intermediate, based on the well-precedented stoichiometric reaction of isocyanides with MNR species.26−35 Laskowski and Hillhouse demonstrated that a dinickel(I) complex supported by N-heterocyclic carbenes can perform the catalytic reaction where it captures a nitrene from mesityl azide and transfers the NMes group to CNR (R = tert-butyl or benzyl).36 A β-diketiminate-supported nickel system can catalytically produce carbodiimides through a similar mechanism, with an excellent scope.37 Heyduk and co-workers © XXXX American Chemical Society
Scheme 1. (Top) Carbodiimide Formation from Isocyanide and Organoazide Substrates; (Bottom) Structures of Known Precatalysts
showed that a redox-active ligand supported zirconium(IV)imido complex catalytically delivers the nitrene group to Received: April 30, 2013
A
dx.doi.org/10.1021/om400379p | Organometallics XXXX, XXX, XXX−XXX
Organometallics
Article
isocyanides.38 In our research, we used a bulky β-diketiminate ligand to stabilize the three-coordinate iron(III) imido complex LtBuFe(NAd), which catalytically transfers NAd to CNCy and CNtBu to form the unsymmetric carbodiimides AdNC NCy and AdNCNtBu.39 Here, we elucidate the details of the mechanism of carbodiimide formation catalyzed by LtBuFe species, using a combination of spectroscopy, kinetic studies, and competition reactions. Our results show that although the resting state is LtBuFe(CNR)3, a monoisocyanide complex is the key intermediate that reacts with azide. The mechanistic studies are consistent with two possibilities in the key C−N bond forming step, with either (a) formation of an iron(III)−imido intermediate LtBuFe(NR)(CNR′) that eliminates RNC NR′ or (b) a concerted step in which N3R attacks coordinated isocyanide in LtBuFe(CNR′) and eliminates N2 without formation of an imidoiron intermediate. The ability of the LtBuFe system to deliver the NR fragment to organic substrates highlights the exceptional potential of unsaturated late transition metal complexes for bond-forming catalysis.
Table 1. Conditions for Catalytic Carbodiimide Formation entry precatalyst
■
RESULTS Catalytic Nitrene Transfer Reactions. In this work, the formally diiron(I) complex LtBuFeNNFeLtBu (1) was the precatalyst for conversion of isocyanides and organoazides into carbodiimides. Heating a mixture of isocyanide (CNR1) and organoazide (N3R2) in C6D6 with 5 mol % of 1 afforded carbodiimides R1NCNR2 within 1 h (Scheme 2). The
R1 (isocyanide)
1
1
2
1
3
1
4
1
5
1
6
1
7
1
2,6-Me2C6H3 2,6-Et2C6H3 2,6-iPr2C6H3 2,6-Me2C6H3 2,6-Et2C6H3 2,6-iPr2C6H3 tert-butyl
8
2
tert-butyl
9
3
tert-butyl
10
4
tert-butyl
11
none
tert-butyl
12
LtBuFeCl
tert-butyl
13
Rieke Fed
tert-butyl
temp (°C)
time (h)
yield (%)
p-tolyl
45
1
91a
p-tolyl
45
1
87a
p-tolyl
45
0.3
83a
4-CF3-C6H3
50
0.5
70a
4-CF3-C6H3
50
0.5
75a
4-CF3-C6H3
50
0.5
80a
1adamantyl 1adamantyl 1adamantyl 1adamantyl 1adamantyl 1adamantyl 1adamantyl
60
1
>95b
80
20
74b
80
14
>95b
80
20
32b
60
120
0c
80
120
0c
80
120
0c
R2 (azide)
a
Isolated yield. bYield determined by 1H NMR integration. cNo product was observed in the 1H NMR spectrum of the reaction mixture. d100 mol % of Rieke iron was used.
Scheme 2. (Top) Catalytic Reaction Examined in This Work; (Bottom) Structures of Precatalysts
mechanistic studies. In control reactions using either LtBuFeCl or microparticulate iron(0) (“Rieke” iron)40 no carbodiimides were formed. EPR Spectroscopy of Iron(I) Isocyanide Complexes. In each reaction, addition of at least 6 equiv of CNR to the precatalyst 1 produced immediate effervescence, consistent with loss of the coordinated N2 and formation of a new iron− isocyanide species. The X-band EPR spectrum of a mixture of 1 with 6 equiv of CNtBu was rhombic with g = [2.085, 2.064, 2.002], identical to that for the low-spin iron(I) complex LtBuFe(CNtBu)3.39 This complex has been crystallographically characterized, showing that it has a square pyramidal geometry around the low-spin iron(I) center.39 Adding an excess of other isocyanides (where R = Cy, Xyl, 2,6-Et2C6H3, 2,6-iPr2C6H3) produced EPR spectra that were similar to LtBuFe(CNtBu)3 and are thus assigned as the corresponding L tBu Fe(CNR) 3 complexes (Figure 1 and Table 2). Hyperfine coupling of the g3 signal (A ≈ 5 × 10−4 cm−1, see Figure S-5) in the 1:1:1 triplet indicates that the electron spin is coupled to a single 14N nuclear spin (I = 1). This coupling is absent in LtBuFe(CO)3, which suggests that the coupling is to an isocyanide ligand. Furthermore, the Cs symmetry of the square pyramidal tris(isocyanide) complexes indicates that only the axial isocyanide ligand is unique, most strongly implicating this ligand as the source of the coupling. This is corroborated by the absence of coupling of the g3 signal in LtBuFe(CNtBu)2 (discussed below), which lacks the axial isocyanide ligand. Therefore, the EPR data indicate that the SOMO is the dz2 orbital that points at the axial ligand. Hyperfine coupling to 14N has been documented in other d7 M−CNR and M−CN complexes.41−43 The average g value is smaller for LtBuFe(CN-Aryl)3 (gav ≈ 2.04) than for LtBuFe(CN-Alkyl)3 (gav ≈ 2.05), which implies
carbodiimide products of these reactions were formed quantitatively by 1H NMR spectroscopy and were isolated in 70−91% yield (Table 1). The iron(I) synthons LMeFeNNFeLMe (2) and LPh3Fe (3) and the cobalt(I) synthon LtBuCoNNCoLtBu (4) were screened as precatalysts to compare their activity to LtBuFeNNFeLtBu for coupling N3Ad and CNtBu (Table 1, entries 7−10). Each of the precatalysts 2, 3, and 4 catalyzed the formation of AdNCNtBu (more than 1 equiv of product was generated per metal), but required higher temperatures (80 °C) and extended reaction times (10−20 h) compared to 1. Precatalyst 4 also afforded a significantly lower yield of carbodiimide. These results indicate that 1 gives the best performance of the four precatalysts, and it was thus chosen for B
dx.doi.org/10.1021/om400379p | Organometallics XXXX, XXX, XXX−XXX
Organometallics
Article
LtBuFe(CNXyl)3, with
