Cobalt-Catalyzed Synthesis of Unsymmetrically - ACS Publications

Jul 27, 2018 - fruit of Pandanus tectorius Parkinson ex Du Roi. Nat. Prod. Res. 2015,. 29, 1437−1441. (45) Besson, M.; Gallezot, P.; Pinel, C. Conve...
0 downloads 0 Views 619KB Size
Letter Cite This: Org. Lett. XXXX, XXX, XXX−XXX

pubs.acs.org/OrgLett

Cobalt-Catalyzed Synthesis of Unsymmetrically N,N‑Disubstituted Formamides via Reductive Coupling of Primary Amines and Aldehydes with CO2 and H2 Zhengang Ke,†,‡ Zhenzhen Yang,† Zhenghui Liu,†,‡ Bo Yu,† Yanfei Zhao,† Shien Guo,†,‡ Yunyan Wu,†,‡ and Zhimin Liu*,†,‡

Org. Lett. Downloaded from pubs.acs.org by UNIV OF SUNDERLAND on 10/22/18. For personal use only.



Beijing National Laboratory for Molecular Sciences, Key Laboratory of Colloid, Interface and Thermodynamics, CAS Research/Education Center for Excellence in Molecular Sciences, Institute of Chemistry, Chinese Academy of Sciences, Beijing 100190, China ‡ University of Chinese Academy of Sciences, Beijing 100049, China S Supporting Information *

ABSTRACT: Herein, a novel route to synthesize unsymmetrically N,N-disubstituted formamides is reported, which is achieved via reductive coupling of primary amine and aldehyde with CO2/H2 over a cobalt-based catalytic system composed of CoF2, P(CH2CH2PPh2)3 and K2CO3. The mechanism investigation indicates that a secondary amine is formed via hydrogenation of the imine originated from aldehyde and primary amine, which further reacts with HCOOH generated from CO2 hydrogenation, resulting in the formation of NNFA finally.

S

pounds,45−47 and hydroformylation of olefin,48−50 and has been widely applied in the organic synthesis. In our previous work,51 we presented an efficient approach to synthesize unsymmetrical NNFAs via hydroamination of aldehyde and amine to unsymmetrical secondary amine, followed by reductive N-formylation of this unsymmetrical secondary amine with CO2 in the presence of phenylsilane, and a series of unsymmetrical NNFAs were obtained via changing aldehydes and amines. Compared to hydrosilanes, molecular hydrogen is less expensive and more easily available, so it is more interesting to use H2 as a reductant in the CO2-involved reductive reactions. In particular, exploring inexpensive and Earth-abundant metal catalysts to synthesize versatile unsymmetrical NNFAs is of significance. We are inspired by our previously reported work regarding Co(BF4)2·6H2O/PP3/K2CO3 system-catalyzed methylation of ketones with menthol.52 Herein, we present a highly efficient cobalt-based catalytic system composed of CoF 2 , P(CH2CH2PPh2)3 (denoted as PP3) and K2CO3 for the synthesis of unsymmetrically NNFAs via reductive coupling of primary amine and aldehyde with CO2/H2. The optimized reaction conditions were explored, and the scopes of aldehydes and primary amines were also examined. It was demonstrated that the catalytic system was very effective for this reaction at 140 °C, affording various unsymmetrical NNFAs in good to excellent yields, together with good functional-group tolerance and broad substrate scope.

ince carbon dioxide (CO2) is nontoxic, abundant, and renewable, its utilization has been given much attention recently. In particular, as a C1 feedstock, CO2 has been widely applied in the synthesis of chemicals1−3 and fuels,4−6 providing various green synthetic routes. For example, N-formylation of amines to formamides using CO2 as a formyl reagent has been widely investigated in the presence of reductants, including H2, hydrosilanes,7−14 and boranes.15−17 Although the utilization of hydrosilanes and boranes could make the reaction proceed under mild conditions, it suffers from poor atom economy and production of organosilicone/organoborane wastes. The reductive formylation of amines with CO2/H2 provides a green strategy for the synthesis of formamides, because H2O is the sole byproduct. Since the pioneering work of catalytic Nformylation of amines with CO2/H2 over Raney nickel catalyst,18 various noble metal catalysts, such as Rh,19 Ru,20−24 Pd,25−28 Ir,29,30 Au,31 and Pd−Au,32 have been developed for the CO2-involved N-formylation of amines, with a focus on achieving high reaction efficiency. Although the noble-metal catalysts are effective for the N-formylation of amines, their high costs hamper their industrial applications. Recently, non-noble metal catalysts, including Mn-,33−35 Fe-,36,37 Co-,38,39 Ni-18 and Cu-based catalysts40−43 have been presented for the N-formylation of amines with CO2/H2, showing promising application potentials. Unsymmetrically N,N-disubstituted formamides (NNFAs) are a class of chemicals with widespread applications in organic and pharmaceutical synthesis, which are generally produced via the formylation of N,N-disubstituted amines. Aldehyde is a type of abundant and low-cost chemical that can be easily obtained from natural products,44 biomass platform com© XXXX American Chemical Society

Received: July 27, 2018

A

DOI: 10.1021/acs.orglett.8b02384 Org. Lett. XXXX, XXX, XXX−XXX

Letter

Organic Letters

(BF4)2·6H2O, Co(acac)2, and Co2(CO)8 were examined, and they were found to also be effective for this reaction, with most of them showing high activity (Table 1, entries 9−14). Fe(OAc)2, Ni(OAc)2·4H2O, and Cu(OAc)2·H2O were also able to catalyze this reaction; however, they displayed much lower activities, compared to most of the cobalt salts (Table 1, entries 15−17). As is well-known, a base is usually needed in the process catalytic hydrogenation of CO2 to HCOOH. Besides K2CO3, other bases including KOH, tBuOK, K3PO4, and Cs2CO3 were tested under the same other conditions (Table 1, entry 1, 18−21), and K2CO3 showed the best performance. The amounts of K2CO3 and PP3 also affected the reductive coupling reaction (see Table S2 in the SI), and 1.5 equiv of K2CO3, together with 5 mol % of PP3, was appropriate for the reaction to afford high product yield. In addition, the solvents had significant influence (Table 1, entries 22−29). Nonpolar solvents, e.g., n-heptane and toluene, almost suppressed the reaction (Table 1, entries 23 and 24), and weakly polar solvents such as THF, 1,4-dioxane, and CH3CN afforded very low yield of 1c (Table 1, entries 25−27). Highly polar aprotic solvents, such as EtOH, DMSO, and DMF, showed better performances, affording a relatively high yield of 1c (Table 1, entries 1, 28, and 29). Other phosphine- or nitrogen-containing ligands, instead of PP3, were tested in this reaction, and it was indicated that they hardly showed any activity (see Table S1 in the SI). This result suggests that PP3 played an important role in the reaction, which may chelate with Co2+ to form active hydrogen complexes, thus enhancing its catalytic activity.37,39 Based on the above results, the optimized reaction conditions were obtained as listed in Scheme 1, under which the generality of the reductive coupling of primary amines, aldehydes with CO2 and H2, was investigated. First, using aliphatic primary amines and aliphatic aldehydes as the substrates, a series of unsymmetrical N-alkyl-N-alkylformamides were obtained in high yields (see Scheme 1, 1c−22c). For example, the coupling of 1b and various chain aliphatic amines or cyclic aliphatic amines with CO2/H2 proceeded well, giving good to excellent product yields (Scheme 1, 1c−11c, 76%−99%). Three isomers of butyl amines showed reactivity in the following order: n-butylamine > iso-butylamine > tertbutylamine, which may be due to the steric effect (Scheme 1, 2c−4c). As expected, the chain length of the chain amines influenced their reactivity, and the product yields decreased with the chain length (Scheme 1, 1c and 5c−8c). The tested cyclic amines including c-hexylamine, c-pentylamine, and 1methylpiperidin-4-amine displayed high activity to react with 1b and CO2/H2, affording corresponding target products in yields of 84%, 84%, and 78%, respectively (see Scheme 1, 9c− 11c). Cyclopentanecarbaldehyde as the aldehyde substrate exhibited similar activity to 1b in this reductive coupling reaction, affording corresponding NNFAs in high yields (Scheme 1, 13c−22c). Encouraged by the above results, we extended the scopes of amines and aldehydes to aromatic aldehydes and primary amines with aromatic nucleus substituents (see Scheme 1, 23c−34c). First, the reaction of 1a and benzaldehyde with CO2/H2 was performed, and a product yield of 77% was obtained (Scheme 1, 23c). Next, more aromatic aldehydes were examined, and it was indicated that all the reductive coupling reactions proceeded well, producing target products in moderate yields of 64%−80% (Scheme 1, 24c−27c). In addition, other aromatic aldehydes, such as 5-methylfurfural, 4-

Hexylamine (1a) and cyclohexanecarboxaldehyde (1b) were selected as model substrates of amine and aldehyde, respectively, to explore the possibility to synthesize Ncyclohexylmethyl-N-hexylformamide (1c) via the reductive coupling of aldehyde and amine with CO2/H2. After screening the catalytic system and reaction conditions (see Table 1, as Table 1. Reductive Coupling of Cyclohexanecarboxaldehyde and n-Hexylamine with CO2 and H2a

entry

catalyst

base

solvent

yield (%)

1 2b 3 4 5c 6d 7e 8f 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29

CoF2 CoF2 CoF2 − CoF2 CoF2 CoF2 CoF2 Co(ClO4)2·6H2O Co(OAc)2·4H2O CoBr2 Co(BF4)2·6H2O Co(acac)3 Co2(CO)8 Cu(OAc)2·H2O Ni(OAc)2·4H2O Fe(OAc)2 CoF2 CoF2 CoF2 CoF2 CoF2 CoF2 CoF2 CoF2 CoF2 CoF2 CoF2 CoF2

K2CO3 K2CO3 − K2CO3 K2CO3 K2CO3 K2CO3 K2CO3 K2CO3 K2CO3 K2CO3 K2CO3 K2CO3 K2CO3 K2CO3 K2CO3 K2CO3 KOH K3PO4 tBuOK Cs2CO3 K2CO3 K2CO3 K2CO3 K2CO3 K2CO3 K2CO3 K2CO3 K2CO3

EtOH EtOH EtOH EtOH EtOH EtOH EtOH EtOH EtOH EtOH EtOH EtOH EtOH EtOH EtOH EtOH EtOH EtOH EtOH EtOH EtOH CH2Cl2 toluene n-heptane THF 1,4-dioxane CH3CN DMF DMSO

93 3 35