Tetrahedron Letters 57 (2016) 4845–4849

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Tetrahedron Letters

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Facile Pd-catalyzed chemoselective transfer hydrogenation of olefinsusing formic acid in water

http://dx.doi.org/10.1016/j.tetlet.2016.09.0590040-4039/� 2016 Elsevier Ltd. All rights reserved.

⇑ Corresponding author. Tel.: +86 15062271613.E-mail address: zym903@126.com (Y. Zeng).

+ HCOOHR2

R1 R3

Pd(OAc)2 (5 mol %)Xantphos (5 mol %)

H2O 90 oC 20 h R2

R1 R3

H

H

Scheme 1. Palladium-catalyzed transfer hydrogenation.

Tianxiang Liu a, Yongming Zeng a,b,⇑, Hongxi Zhang a, Ting Wei a, Xia Wu a, Nan Li a

aDepartment of Chemistry and Applied Chemistry, Changji University, Changji 831100, Xinjiang, Chinab State Key Laboratory of Coordination Chemistry, Nanjing University, Nanjing 210093, China

a r t i c l e i n f o a b s t r a c t

Article history:Received 1 July 2016Revised 11 September 2016Accepted 18 September 2016Available online 19 September 2016

Keywords:Transfer hydrogenationPalladiumChemoselectiveEnvironmentally friendly catalystWater

An effective Pd-catalyzed reduction of olefins in water using formic acid is disclosed. A wide range of sat-urated hydrocarbons are obtained with an excellent conversion and remarkable chemoselectivity undermild reaction conditions. This protocol is more advantageous and less cumbersome owing to the use ofHCOOH as a hydrogen source, water as a solvent, and simple workup procedure.

� 2016 Elsevier Ltd. All rights reserved.

Introduction

The chemoselective hydrogenation of double bond of olefins is awell-known protocol in organic chemistry, which has been used inthe synthesis of pharmaceutical, fine chemicals, and functionalmaterials.1 While different approaches have been developed forthe synthesis of this class of molecules, metal catalyzed transferhydrogenations is most commonly used both in laboratory and inindustry, which avoid some of the technical and safety concernsassociated with using molecular hydrogen gas in the presence ofPd/C under high pressure and high temperatures.1,2 Several transi-tion-metal catalyzed transfer hydrogenation with alcohol,3 amine,4

formate,5 and silicon hydride6 as the hydrogen donor has been con-tinuously explored. Recently, a number of formic acid as a environ-mental-friendly hydrogen donor have been widely studied.7 Inparticular, Brunel8 reported work on a homogeneous catalytic pal-ladium systems for chemoselective transfer hydrogenation usingformic acid. Nevertheless, the functional group compatibility andlow yields are still challenges. Therefore, the development of a verypromising alternative method for effective transfer hydrogenationexhibiting the necessary selectivity and mildness is still desirable.9

Herein, we wish to report a simple, economical, and effective wayto chemoselectively reduce the olefins in the presence of Pd cata-lyst using formic acid as hydrogen source in water (Scheme 1).

Results and discussion

To explore the reaction conditions of the transfer hydrogenationreaction of olefins with formic acid as a hydrogen source, chalcone(1a) was selected as the test substrate and the results are listed inTable 1. For the optimization study, a range of ligands were initiallyexamined. In the presence of the ligand such as PPh3, dppe, dppp,dppb, and dppf, treating 1a with HCOOH, and 5 mol % Pd(OAc)2 intoluene at 90 �C for 20 h gave saturated ketone 2a in low yield(Table 1, entries 1–5). Noteworthy, when the reaction was per-formed using bidentate ligand Xantphos (Table 1, entry 6), anincrease in yield (92%) for the corresponding ketone 2a wasobserved. The reduction was ineffective without any phosphorusligands (Table 1, entry 7). Among the solvents examined to testthe solvent effect, ethanol and water were found to be optimalfor chemoselective transfer hydrogenation, giving the product 2ain 99% yield (Table 1, entries 6, 8–13). However, water was selectedas solvent, due to its being more environmentally friendly, andcheaper. The effects of various Pd catalysts were investigated, Pd(OAc)2 has been proved more effective (Table 1, entries 12, 14,and 15). On decreasing the ratio of Pd(OAc)2 and Xantphos, a poor

Table 1Studies of the reaction conditionsa

O O

H

H

+ HCOOHPd(OAc)2. Ligand

aSolvent

Entry [Pd] Ligand Solvent Yieldb (%)

1 Pd(OAc)2 PPh3 Toluene Trace2 Pd(OAc)2 dppe Toluene 723 Pd(OAc)2 dppp Toluene 784 Pd(OAc)2 dppb Toluene 815 Pd(OAc)2 dppf Toluene 756 Pd(OAc)2 Xantphos Toluene 927 Pd(OAc)2 — Toluene 08 Pd(OAc)2 Xantphos DMF 629 Pd(OAc)2 Xantphos THF 7110 Pd(OAc)2 Xantphos DCM 7811 Pd(OAc)2 Xantphos Ethanol 9912 Pd(OAc)2 Xantphos Water 9913 Pd(OAc)2 Xantphos Dioxane 6514 Pd(PPh3)4 Xantphos Water 815 PdCl2 Xantphos Water 4316c Pd(OAc)2 Xantphos Water 8517d Pd(OAc)2 Xantphos Water 8818e Pd(OAc)2 Xantphos Water 019f Pd(OAc)2 Xantphos Water 7220g Pd(OAc)2 Xantphos Water 9321h Pd(OAc)2 Xantphos Water 58

a The reactions were carried out with substrate 1a (0.50 mmol), HCOOH (1.00 mmol), [Pd] (0.025 mmol), and ligand (0.025 mmol, P/Pd = 2:1) in toluene (0.50 mL) at 90 �Cfor 20 h unless otherwise stated.

b Isolated yield.c With Pd(OAc)2 (0.025 mmol) and Xantphos (0.050 mmol).d With Pd(OAc)2 (0.020 mmol) and Xantphos (0.020 mmol).e The absence of HCOOH.f 1.0 equiv of HCOOH.g 3.0 equiv of HCOOH.h At 80 �C.

Table 2Pd-catalyzed chemoselective transfer hydrogenation of olefinsa

+ HCOOH

R2

R1 R3

Pd(OAc)2 (5 mol %)Xantphos (5 mol %)

H2O 90 oC 20 h R2

R1 R3

H

H

Entry Substrate Product Yieldb (%)

Ph

O

XPh

O

H

H

X

1 X = p-H 1a 2a 992 X = p-Me 1b 2b 993 X = p-OMe 1c 2c 98

Ph R

O

Ph R

OH

H4 R = CH3 1d 2d 955 R = H 1e 2e 966 R = OH 1f 2f 997 R = OMe 1g 2g 97

8 OPh

O

1hOPh

OH

H 2h91

RH

HR

9 R = p-H 1i 2i 9910 R = p-OMe 1j 2j 9711 R = p-NH2 1k 2k 91

4846 T. Liu et al. / Tetrahedron Letters 57 (2016) 4845–4849

Table 2 (continued)

Entry Substrate Product Yieldb (%)

12 N 1lN

H

H 2l89

13Ph

Ph1m

PhPh

H

H 2m95

14

CN

1n

H

H

CN

2n95

15 1o

HH

2o90

16 HO OMe1p

HH

HO OMe 2p89

17

O

O

1q O

OH

H 2q92

18

O

1r

O

H

H 2r75

19

O

1s

OHH

2s90

20 OH

O

1tOH

OH

H 2t99

21 OH

O

1uOH

OH

H 2u99

22 HOOH

O

O

1v HOOH

O

O H

H 2v94

23 OPh

O

1wOPh

OH

H 2w 88

24 H2N

O

1x H2N

O

H

H

2x94

25c OH

1y

H

H

H

HOH2y

92

a The reactions were carried out with substrate 1 (0.50 mmol), HCOOH (1.00 mmol), Pd(OAc)2 (0.025 mmol), and Xantphos (0.025 mmol) in water (0.50 mL) at 90 �C for20 h.

b Isolated yield.c With HCOOH (2.00 mmol).

(10 mmol)

Pd(OAc)2 (5 mol %)

HCOOH (2.0 equiv) H2O, 90 oC, 20 h

Xantphos (5 mol %)

91 % yield

OH

O

OH

OH

H

Scheme 2. Gram scale transfer hydrogenation reaction.

T. Liu et al. / Tetrahedron Letters 57 (2016) 4845–4849 4847

conversion was obtained (85%, Table 1, entry 16). Only moderateyield was isolated using catalyst in lower loading (4 mol % Pd(OAc)2 and 4 mol % Xantphos) (88%, Table 1, entry 17). No desired

adduct was formed in the absence of HCOOH (Table 1, entry 18),suggesting that HCOOH maybe decisive in the reaction. Notably,lower yield (72%) was achieved in the presence of 5 mol % Pd(OAc)2 and 5 mol % Xantphos in water at 90 �C for 20 h when theamount of HCOOH was reduced to 1.0 equiv (Table 1, entry 19).However, the product 2a was obtained in 93% yield when the reac-tion could proceed in the presence of 3.0 equiv of HCOOH (Table 1,entry 20). This reaction was assessed at a relatively lower reactiontemperature and also proceeded smoothly, giving ketone 2a in 58%yield (Table 1, entry 21).

PdPP

PdPH2P

HOH

HO

H OH

O

R1

R2R1

R2

H

PdPP

OH

O

PdPP

OH

O

CO2

R1

R2

H

H

H

R1

R2

H

PdPP

H

R1

R2

R1

R2

PdPP

HH

CO2

R1

R2

H

H

1

2

3

4

2'

4'

5 5'

0 PdPP

0

Scheme 3. Proposed catalytic cycle for transfer hydrogenation.

4848 T. Liu et al. / Tetrahedron Letters 57 (2016) 4845–4849

To evaluate the general applicability of this methodology, awide variety of carbon–carbon double bonds were investigated(Table 2). The transfer hydrogenation reaction was conducted, pro-viding the corresponding desired in 75–99% yields with remark-able chemoselective (Table 2, entries 1–25). Various unsaturatedketones were smoothly reduced in good yields (Table 2, entries1–4, 17–19). Electron-donating aromatic and alkyl substituted a-enones were effective substrates, giving their corresponding satu-rated ketones in 95–99% yield (Table 2, entries 2–4), whereas sub-strates with halogen or nitro group in the aromatic ring wereunsuccessful under the current reaction conditions. Cyclic enoneswere also reduced in excellent yield of 75% and 90%, respectively(Table 2, entries 18 and 19), implying that the steric hindrancehad no clear effect. The transfer hydrogenation can be extendedto terminal and disubstituted alkenes to afford the correspondingproducts in good yields (Table 2, entries 9–13, 15, and 16). Note-worthy, the reaction of 4-amino styrene also proceeded smoothly.A wide variety of functional groups such as aldehyde, ester, acid,and amide were not affected by this protocol, and only olefinicwas successfully converted to their saturated forms in 80–90%yields (Table 2, entries 5–8 and 20–25). Particularly, for isolatedand conjugated olefins were all tolerable under the optimized con-ditions (Table 2, entries 20, 21, and 25). Moreover, when phenyles-ters was subjected to the present chemoselective reduction, thesaturated esters 2h and 2wwere obtained in 88–91% yield (Table 2,entries 8 and 23). The transfer hydrogenated process can alsoapplied to a,b-unsaturated cyanide without difficulty, providingproduct 2z in 95% yield (Table 2, entry 14). It is noteworthy thatthe procedure can even be performed under air. Furthermore, thechemoselective reduction of olefin was carried out on gram scalewith the use of sealed reaction vessel, and saturated product wasobtained in 91% yield (Scheme 2).

A precise understanding of the reaction mechanism awaits fur-ther study. According to literature data,8 a plausible catalytic cycleis proposed in Scheme 3. The oxidative addition of formic acid onPd(0) led to the formation of key intermediate palladium hydridecomplex 3, which hydropalladated the olefin substrate 1 to affordnew hydrido palladium complex 5. Upon reduction elimination,complex 5 gave the expected saturated compound 2 with regener-ation of Pd(0) catalyst.

Conclusion

In conclusion, an effective Pd-catalyzed reduction of olefins inwater using formic acid is disclosed. A wide range of saturated

hydrocarbons are obtained with an excellent conversion andremarkable chemoselectivity under mild reaction conditions. Thisprotocol is more advantageous and less cumbersome owing tothe use of readily available HCOOH as a hydrogen source, wateras a solvent, and simple operation. Furthermore, the asymmetricreaction of Pd-catalyzed transfer hydrogenation is currently inprogress.

Acknowledgment

We are grateful to the Natural Science Foundation of XinjiangProvince (2016D01C009) for the financial help.

Supplementary data

Experimental procedures, characterization data of NMR spectraare available free of charge via the Internet. Supplementary dataassociated with this article can be found, in the online version, athttp://dx.doi.org/10.1016/j.tetlet.2016.09.059.

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