Letter pubs.acs.org/acscatalysis
Palladium-Catalyzed Migratory Insertion of Isocyanides for Synthesis of C‑Phosphonoketenimines Qiang Yang,† Chong Li,† Ming-Xing Cheng,† and Shang-Dong Yang*,†,‡ †
State Key Laboratory of Applied Organic Chemistry, Lanzhou University, Lanzhou 730000, People’s Republic of China State Key Laboratory for Oxo Synthesis and Selective Oxidation, Lanzhou Institute of Chemical Physics, Chinese Academy of Sciences, Lanzhou, 730000, People’s Republic of China
‡
ACS Catal. 2016.6:4715-4719. Downloaded from pubs.acs.org by IOWA STATE UNIV on 01/21/19. For personal use only.
S Supporting Information *
ABSTRACT: An efficient method for the synthesis of Cphosphonoketenimines through palladium-catalyzed migratory insertion of isocyanides has been developed for the first time. This procedure tolerates wide functional groups and has a good atom economy. Further transformations of the products, which are useful building blocks for the β-aminophosphonates, β-aminovinylphosphonates, and C-phosphorylated tetrazoles, indicate potential synthetic utility. KEYWORDS: C-phosphonoketenimines, palladium, isocyanides, phosphonylated, synthetic method Scheme 1. Methods for the Synthesis of CPhosphonoketenimines
K
etenimines are an important class of compounds that are recognized as useful synthetic intermediates or synthons in chemistry. Since Staudinger reported the first ketenmines in 1920,1 much of the knowledge of these analogous compounds has flourished within the last hundred years.2 Because of their unique properties related to the presence of an ethylene-like C− C double bond and an azomethine-like C−N double bond, ketenimines have opened a wide range of available reaction paths. It has been proved that ketenimines can undergo many useful reactions such as nucleophilic additions, radical additions, biradical cyclizations, electrocyclizations, sigmatropic rearrangements, and cycloaddition reactions.2c,d,3 On the other hand, isocyanides,4 which may function as a nucleophile, an electrophile, and a radical, are ideal reagents for the synthesis of ketenimines.2d,5 Organophosphorus compounds,6 such as phosphonates and phosphine oxines, are useful in medicinal chemistry,7 agricultural chemistry,8 materials,9 biochemistry,10 and organic synthesis.11 Considering these diverse applications, the development of new and efficient methods to synthesize organophosphorus compounds has became an intensive topic of discussion in organic synthetic chemistry.12 A ketenimine bearing a phosphoryl group as a multifunctional substituent was reported years ago.13 Compared to partial ketenimines, which are difficult to isolate just as intermediates in reactions,2g,14 phosphonoketenimines are more stable and easier to control. Notably, the introduction of a phosphoryl group bonded to the ketenimine would be expected to improve not only the reactivity of the ketenimine but also its value as a synthetic reagent.13a However, such reports are particularly rare; for the transition-metal catalyst in particular, there are no reports. In 1979, Ohshiro and Motoyoshiya reported the first synthesis of C-phosphonoketenimines (Scheme 1, path © 2016 American Chemical Society
a).13a Then, an alternative preparation of C-phosphonoketenimines was reported by Kolodyazhnyi and Yakovlev in 1980 (Scheme 1, path b).13c These approaches suffer from limitations such as complicated procedures and narrow substrate scope. Considering the importance of ketenimines and continuing our research interest in synthesis of new-style organophosphorus compounds,15 for the first time, we report an efficient method to synthesize stable ketenimines bearing a phosphoryl group through palladium-catalyzed migratory insertion of isocyanides with α-halophosphonates and α-halophosphine oxides. The investigation was started from tert-butyl isocyanide (1a) with diethyl (bromo(phenyl)methyl)phosphonate (2aa) in the presence of 10 mol % Pd(OAc)2 and 2 equiv of K2CO3 in 1,4dioxane under argon atmosphere at 85 °C (see Table S1 (entry Received: May 4, 2016 Revised: May 31, 2016 Published: June 15, 2016 4715
DOI: 10.1021/acscatal.6b01253 ACS Catal. 2016, 6, 4715−4719
Letter
ACS Catalysis
indicated by the control experiments (Table 1, entries 16 and 17). Having the optimized reaction conditions in hand, the scope of various isocyanides was tested. As shown in Scheme 2, alkyl
1) in the Supporting Information). To our delight, diethyl (2(tert-butylimino)-1-phenylvinyl)phosphonate (4a) was isolated in 23% yield. Encouraged by this result, we further screened solvents, catalysts, and bases, and we used different ratios of 1a and 2aa under an argon atmosphere extensively. Unfortunately, we did our best to increase the yield of 4a but only observed 55% under the reaction conditions with [Pd(C3H5)Cl]2 (5 mol %), Cs2CO3 (1.4 equiv), and 1a/2aa (1.0/1.5) in 1,2-dichloroethane under an argon atmosphere at 85 °C (see Table S1 for details). While performing this reaction, we also detected the formation of some debrominated byproducts of diethyl benzylphosphonate that were produced simultaneously in the reaction system. This discovery prompted us to consider that the C−Br bond of 2aa is too active to decompose. In light of this initial finding, we switched 2aa to diethyl (chloro(phenyl)methyl)phosphonate (2ab), which had lower reaction activity. To our surprise, we were pleasant to get the yield of 4a in 84% (Table 1, entry 1)
Scheme 2. Investigation of Various Isocyanides and αChlorobenzylphosphonate 2aba,b
Table 1. Optimization of Reaction Conditionsa
entry
Pd (mol %)
base
solvent
1 2 3
[Pd(C3H5)Cl]2 (5) [Pd(C3H5)Cl]2 (5) [Pd(C3H5)Cl]2 (5)
Cs2CO3 Cs2CO3 Cs2CO3
4 5 6 7 8 9 10 11 12 13 14c 15d 16 17
[Pd(C3H5)Cl]2 (5) Pd(OAc)2 (10) Pd(PPh3)Cl2 (10) Pd(dba)2 (10) [Pd(C3H5)Cl]2 (5) [Pd(C3H5)Cl]2 (5) [Pd(C3H5)Cl]2 (5) [Pd(C3H5)Cl]2 (3) [Pd(C3H5)Cl]2 (1) [Pd(C3H5)Cl]2 (5) [Pd(C3H5)Cl]2 (5) [Pd(C3H5)Cl]2 (5)
Cs2CO3 Cs2CO3 Cs2CO3 Cs2CO3 K3PO4 K2CO3 KOAc Cs2CO3 Cs2CO3 Cs2CO3 Cs2CO3 Cs2CO3 Cs2CO3
DCE toluene 1,4dioxane CH3CN DCE DCE DCE DCE DCE DCE DCE DCE DCE DCE DCE DCE DCE
[Pd(C3H5)Cl]2 (5)
temp, T (°C)
yield (%)b
85 85 85
84 73 69
85 85 85 85 85 85 85 85 85 60 85 85 85 85
49 74 41 82 33 56
