CC BY-NC-ND 4.0 · SynOpen 2020; 04(04): 116-122
DOI: 10.1055/s-0040-1705980
paper

Ammonia–Borane-Mediated Reduction of Nitroalkenes

Chiara Faverio
,
Monica Fiorenza Boselli
,
Laura Raimondi
,
M.B. thanks MIUR for funding through project PRIN 2017 ‘NATURECHEM’. M.B. thanks Università degli Studi di Milano for the PSR 2019-financed project ‘Catalytic Strategies for the Synthesis of High Added-Value Molecules from Bio-Based Starting Materials’. M.B. thanks the ITN-EID project Marie Sklodowska-Curie Actions Innovative Training Network - TECHNOTRAIN H2020-MSCA-ITN-2018 Grant Agreement 812944. www.technotrain-ITN.eu.
 


Abstract

Ammonia borane (AB) has been successfully employed in the reduction of nitroalkenes. A variety of nitrostyrenes and alkyl-substituted­ nitroalkenes were chemoselectively reduced to the corresponding nitroalkanes, in short reaction time, with an atom-economic, simple experimental procedure that also works with α- and β-substituted nitroolefins.


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Ammonia borane (AB) is attracting considerable attention as a convenient material for hydrogen storage and release.[1] [2] However, considering atom economy principles, it is also a relatively inexpensive and useful reduction reagent for developing new green synthetic transformations.

Ammonia borane could act as a convenient replacement for the well-known metal hydrides (sodium borohydride and derivatives), and as a safer and greener replacement[3] of Hantzsch esters, which generate a significant amount of waste (the oxidized pyridine needs to be removed and separated from the reaction product). Reduction with ammonia borane of carbonyl derivatives, imines and amides has been described in detail.[4] One the other hand, the AB-mediated reduction of alkenes is less developed[5] and only highly electron-deficient alkenes bearing two electron-withdrawing groups (esters or nitriles) have been successfully reduced (Scheme [1]).[6] The presence of a catalytic additive is required to accomplish the reduction of unsaturated esters.[7]

Zoom Image
Scheme 1 Chemoselective AB-mediated reduction of nitroalkenes

Herein, we wish to report, for the first time, the use of ammonia borane in the reduction of nitroalkenes. A variety of nitrostyrenes and alkyl-substituted nitroalkenes can be chemoselectively reduced to the corresponding nitro­alkanes, without need for catalyst or additive, in a short time and with a straightforward experimental procedure that is applicable to both α- and β-substituted nitroalkenes. After a simple aqueous work up, the reaction product can be obtained by evaporation of the organic solvent, in many cases as the sole or major product (see the Supporting Information).

We decided to investigate the reaction of ammonia borane with β-nitrostyrene as a model reaction (Scheme [2]) in which experimental parameters, such as solvent, temperature, stoichiometry, and reaction time, were studied.

Zoom Image
Scheme 2 AB-mediated reduction of β-nitrostyrene

A detailed optimization work was performed to obtain the best yields under the most convenient experimental conditions, and to minimize the formation of the dimeric by-products 3a and 3b, thus simplifying the isolation procedure of the nitroalkane;[8] selected data are collected in Table [1].

Table 1 Nitrostyrene Reduction: Optimization Studiesa (Scheme [2])

Entry

Solvent

T (°C)

Time (h)

Concn (M)

Yield 2 (%)b

1

MeOH

25

18

0.01

61

2

MeOH

25

18

0.1

40

3

CH3CN

25

18

0.01

12

4

MeOH

60

4

0.1

53

5

EtOH

60

4

0.1

33

6

n-BuOH

60

4

0.1

41

7c

MeOH

60

4

0.1

43

8d

MeOH

60

4

0.1

55

9

MeOH

60

4

0.05

60

10e

THF

60

4

0.1

40

11f

MeOH

60

4

0.1

47

a Typical reaction conditions: AB (1 mol equiv), no additive. For the general procedure and work-up see the experimental section.

b Isolated yield after chromatographic purification.

c 2 mol equiv of AB were used.

d 4 mol equiv of AB were used.

e 0.2 mol equiv of urea was added.

f 0.2 mol equiv of Schreiner thiourea were added.

Ammonia borane was typically added to a solution of nitroalkene at 25 °C and then the reaction was stirred for 4–24 hours, depending on the experimental conditions. Initially, the reduction was carried out at 25 °C, in methanol at 0.01–0.1 M substrate concentration. After 18 hours, product 2 was isolated in 61% yield (Table [1], entry 1) with minor amounts of the dimer 3, as mixture of isomers (less than 15%). To accelerate the reaction and suppress by-product formation, the reaction was performed at 60 °C in methanol. After only 4 hours the product was obtained in 53% yield after chromatographic purification (entry 4). Lower yields were observed other alcohol solvents such as ethanol or n-butanol, whereas in solvents such as THF, DCM or acetonitrile, the reduction was inefficient. When the reduction was performed in more concentrated solutions, similar yields of nitroalkane were observed, but with increased amounts of the dimeric product. The use of excess of ammonia borane did not bring any significant improvement to the yield or the selectivity of the reaction. Ultimately, the best compromise was found using 0.05 M substrate concentration, with 1 mol equiv of AB for 4 hours at 60 °C; under these conditions the product 2 was isolated in 60% yield, with minor amounts of by-product 3.

Finally, the use of urea and thiourea derivatives was investigated, especially with the aim to suppress the formation of dimeric material. By employing urea as additive in methanol, low yields were observed, while somewhat better results were observed in THF. More interesting results were achieved by using Schreiner thiourea (1,3-bis(3,5-bis(trifluoromethyl)phenyl)thiourea). In this case, the reaction afforded 2 in good yield with very minor amounts of dimers 3. The use of (thio)urea derivatives opens the way towards the development of chiral catalysts that can be used to promote the enantioselective reduction of β-substituted β-nitrostyrenes to the corresponding nitroalkanes, which are valuable precursors of chiral amines (see below).

The scope of the reaction was then investigated with differently substituted aryl and alkyl nitroalkenes (for experimental details on nitroalkene preparation see the Supporting Information), reacting with 1 mol equiv of ammonia borane in methanol for 4 hours at 60 °C. The results obtained on the reduction of a range functionalized nitrostyrenes are summarized in Scheme [3].

Zoom Image
Scheme 3 AB-mediated reduction of functionalized β-nitrostyrenes

The reaction was successfully performed with a range of nitrostyrenes. Electron-rich nitroalkenes were reduced in fair to very good yields, up to 85% (see products 411 in Scheme [3]). The reduction of substrates bearing electron-withdrawing groups afforded the corresponding nitro­alkanes 1215 in yields typically ranging from 45 to 60%. The methodology was also extended to aliphatic nitro­alkenes (Scheme [4]).

Zoom Image
Scheme 4 AB-mediated reduction of β-nitroalkenes

Ammonia borane proved to be an efficient reagent for the reduction of both linear and branched aliphatic nitro­alkenes, affording the expected products in fair to excellent yields. Notably, the nitro derivative 20 was isolated in 63% yield, with complete chemoselectivity, by reduction of the corresponding nitrobutadiene.[9]

The reaction worked very well with either α- or β-substituted nitrostyrenes and improved yields for product 21 were obtained when 3 mol equiv of AB were employed; thus affording 21 in 66% yield after 6 hours. This result opens the way towards the development of new catalytic, asymmetric, atom-economical and convenient strategies for the synthesis of chiral nitroalkanes, which are valuable precursors of chiral amines.[10]

α-Substituted nitroalkane 22 was isolated in 80% yield and the reaction was conducted on a gram scale, without significant difference in yield (76%). It is worth noting that, for both compounds 21 and 22, after a simple aqueous work up, NMR analysis of the crude reaction mixture showed only the desired nitroalkane, without the need for chromatographic purification (see NMR spectra in the Supporting Information).

Based on previous reports,[11] a proposed reaction mechanism is shown in Scheme [5]. The first step is the transfer of a hydride from BH3 to the β-position of the nitroalkene, together with the hydroboration of the C–C double bond. The intermediate is then proposed to convert slowly into the product by intramolecular transfer of a H atom from the NH3 residue, thus realizing a BH2=NH2 species that might be involved in the reduction of another equivalent of the olefin.[12]

Zoom Image
Scheme 5 Proposed mechanism for the AB-mediated reduction of β-nitroalkenes

In conclusion, we have developed a chemoselective reduction of nitroalkenes to nitroalkanes, using ammonia borane in methanol. The methodology works with aryl- and alkyl-substituted nitroolefins, it affords the products after a simple aqueous work up, and relies on the use of the atom-economical, very convenient and inexpensive reagent BH3·NH3. The reaction proceeds smoothly with α- and β-substituted nitroalkenes, thus paving the way for development of enantioselective catalytic reduction of nitro­alkenes, which are valuable precursors of chiral amines.

Commercial grade reagents and solvents were used without further purification. trans-β-Nitrostyrene [CAS Reg. No. 5153-67-3], trans-β-methyl-β-nitrostyrene [CAS Reg. No. 705-60-2] and 1-nitro-1-cyclohexene [CAS Reg. No. 2562-37-0] were purchased from Sigma Aldrich and were used without further purification. Ammonia borane [CAS Reg. No. 13774-81-7] was purchased by Sigma Aldrich and was used without further purification.

1H, 19F, and 13C NMR spectra were recorded at 300 MHz with a Bruker AV 300 instrument. The chemical shifts are reported in ppm (δ) referenced to tetramethylsilane (TMS). Mass spectrometric and accurate mass analyses were carried out with a VG AUTOSPEC-M246 spectrometer (double-focusing magnetic sector instrument with EBE geometry­) equipped with an EI source. Reactions and chromatographic purifications were monitored by analytical thin-layer chromatography (TLC) using silica gel 60 F254 pre-coated glass plates and visualized using UV light, vanillin or KMnO4. Purification of the products was performed by flash column chromatography using silica gel 230–400 mesh. Dry solvents used were commercially available and they were stored under nitrogen over molecular sieves. Microwave reactions were conducted with a CEM Discover SP microwave with an irradiation power of 200 W and reaction temperature of 90 °C for 1 hour.

Aryl-substituted and alkyl-substituted nitroalkenes were prepared from the corresponding aldehydes and nitromethane according to published procedures and purified by crystallization from EtOH (see the Supporting Information).


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Reduction of Nitroalkenes; General Procedure

Caution : Readily reduced, flammable compounds (e.g., acetone) may combust upon contact with ammonia borane.

A solution of nitroalkene (0.4 mmol) in anhydrous MeOH (8 mL) was prepared in a 25 mL two-necked round-bottom flask fitted with a condenser. Ammonia borane (12 mg, 0.4 mmol) was added to the solution at r.t. and the reaction flask was placed in an oil bath (previously heated to 60 °C). After 4 hours, the reaction mixture was cooled to r.t. and the solvent was evaporated under reduced pressure. The residue was dissolved in dichloromethane (8 mL) and washed with water (5 mL). The aqueous phase was extracted once with dichloromethane (5 mL) and the combined organic phases were dried over Na2SO4, filtered and the solvent was evaporated under reduced pressure. If necessary, the crude product was purified by rapid filtration through silica.


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2-Phenylnitroethane (2)

The crude product was purified by column chromatography on silica gel, eluting with hexane/EtOAc 95:5 to afford the title product as a colorless oil. All analytical data are in agreement with the literature.[13]

1H NMR (300 MHz, CDCl3): δ = 7.37–7.19 (m, 5 H), 4.61 (t, J = 7.4 Hz, 2 H), 3.32 (t, J = 7.4 Hz, 2 H).

13C NMR (75 MHz, CDCl3): δ = 135.78, 129.00, 128.63, 127.47, 76.30, 33.46.


#

((2R,3S)-2,4-Dinitrobutane-1,3-diyl)dibenzene (3a)

Isolated as a pale-yellow oil.

1H NMR (300 MHz, CDCl3): δ = 7.47–7.38 (m, 3 H), 7.29– 7.24 (m, 5 H), 7.00 (dd, J = 7.1, 2.6 Hz, 2 H), 4.99 (td, J = 10.3, 3.5 Hz, 1 H), 4.83 (dd, J = 13.1, 10.2 Hz, 1 H), 4.64 (dd, J = 13.1, 4.3 Hz, 1 H), 4.08 (td, J = 10.1, 4.3 Hz, 1 H), 3.14 (dd, J = 14.6, 10.7 Hz, 1 H), 2.86 (dd, J = 14.6, 3.5 Hz, 1 H).

13C NMR (75 MHz, CDCl3): δ = 134.59, 134.11, 129.95, 129.46, 129.11, 128.67, 128.14, 127.95, 91.82, 77.00, 47.30, 38.32.

MS(EI+): m/z calcd for C16H16N2O4: 300.111007; found: 300.102000.


#

((2R,3R)-2,4-Dinitrobutane-1,3-diyl)dibenzene (3b)

Isolated as a pale-yellow solid.

1H NMR spectrum is in agreement with the literature, but the 13C NMR spectrum differs for some signals with respect to the literature.[14]

1H NMR (300 MHz, CDCl3): δ = 7.39–7.35 (m, 3 H), 7.33–7.28 (m, 3 H), 7.20–7.13 (m, 4 H), 5.14 (dt, J = 9.5, 5.5 Hz, 1 H), 4.99 (dd, J = 13.8, 6.6 Hz, 1 H), 4.83 (dd, J = 13.8, 7.9 Hz, 1 H), 4.11–4.05 (m, 1 H), 3.26 (dd, J = 14.5, 9.5 Hz, 1 H), 3.11 (dd, J = 14.5, 5.1 Hz, 1 H).

13C NMR (75 MHz, CDCl3): δ = 134.66, 133.31, 129.50, 129.41, 129.21, 128.94, 128.22, 127.93, 90.22, 76.36, 46.50, 36.99.


#

2-p-Tolylnitroethane (4)

The crude product was purified by column chromatography on silica gel, eluting with hexane/EtOAc 95:5 to afford the title product as a pale-yellow oil (64% yield). All analytical data are in agreement with the literature.[15]

1H NMR (300 MHz, CDCl3): δ = 7.17 (d, J = 8.2 Hz, 2 H), 7.12 (d, J = 8.2 Hz, 2 H), 4.61 (t, J = 7.4 Hz, 2 H), 3.30 (t, J = 7.4 Hz, 2 H), 2.36 (s, 3 H).

13C NMR (75 MHz, CDCl3): δ = 137.17, 132.68, 129.71, 128.52, 76.51, 33.16, 21.11.


#

2-(4-Hydroxyphenyl)-1-nitroethane (5)

The crude mixture was purified by column chromatography on silica gel, eluting with hexane/EtOAc 6:4 to afford the title product as a pale-orange oil (83% yield). All analytical data are in agreement with the literature.[16]

1H NMR (300 MHz, CDCl3): δ = 7.05 (d, J = 8.5 Hz, 2 H), 6.78 (d, J = 8.5 Hz, 2 H), 5.90 (brs, 1 H), 4.56 (t, J = 7.3 Hz, 2 H), 3.22 (t, J = 7.3 Hz, 2 H).

13C NMR (75 MHz, CDCl3): δ = 155.10, 129.89, 127.67, 115.92, 76.74, 32.74.


#

1-Methoxy-4-(2-nitroethyl)-benzene (6)

The crude product was purified by column chromatography on silica gel, eluting with hexane/EtOAc 8:2 to afford the title product as a yellow oil (58% yield). All analytical data are in agreement with the literature.[17]

1H NMR (300 MHz, CDCl3): δ = 7.12 (d, J = 8.6 Hz, 2 H), 6.85 (d, J = 8.7 Hz, 2 H), 4.56 (t, J = 7.3 Hz, 2 H), 3.78 (s, 3 H), 3.24 (t, J = 7.3 Hz, 2 H).

13C NMR (75 MHz, CDCl3): δ = 159.01, 129.71, 127.72, 114.44, 76.67, 55.36, 32.77.


#

1-Methoxy-2-(2-nitroethyl)benzene (7)

The crude mixture was purified by column chromatography on silica gel, eluting with hexane/EtOAc 85: 15 to afford the title product as a pale-yellow oil (78% yield). All analytical data are in agreement with the literature.[18]

1H NMR (300 MHz, CDCl3): δ = 7.27 (td, J = 7.8, 1.8 Hz, 1 H), 7.15 (dd, J = 7.4, 1.8 Hz, 1 H), 6.97–6.82 (m, 2 H), 4.61 (t, J = 7.3 Hz, 2 H), 3.85 (s, 3 H), 3.32 (t, J = 7.4 Hz, 2 H).

13C NMR (75 MHz, CDCl3): δ = 157.57, 130.78, 128.96, 123.97, 120.83, 110.50, 74.82, 55.33, 29.22.


#

1-Methoxy-3-(2-nitroethyl)benzene (8)

The crude mixture was purified by column chromatography on silica gel, eluting with hexane/EtOAc 8:2 to afford the title product as a pale-yellow oil (60% yield). All analytical data are in agreement with the literature.[19]

1H NMR (300 MHz, CDCl3): δ = 7.25 (t, J = 7.9 Hz, 1 H), 6.83–6.74 (m, 3 H), 4.60 (t, J = 7.4 Hz, 2 H), 3.80 (s, 3 H), 3.29 (t, J = 7.4 Hz, 2 H).

13C NMR (75 MHz, CDCl3): δ = 160.10, 137.29, 130.09, 120.86, 114.54, 112.79, 76.25, 55.31, 33.52.


#

2-Methoxy-4-(2-nitroethyl)phenol (9)

The crude mixture was purified by column chromatography on silica gel, eluting with hexane/EtOAc 65:35 to afford the title product as a yellow oil (76% yield). All analytical data are in agreement with the literature.[20]

1H NMR (300 MHz, CDCl3): δ = 6.85 (d, J = 8.5 Hz, 1 H), 6.71–6.67 (m, 2 H), 5.64 (s, 1 H), 4.57 (t, J = 7.3 Hz, 2 H), 3.86 (s, 3 H), 3.23 (t, J = 7.3 Hz, 2 H).

13C NMR (75 MHz, CDCl3): δ = 146.84, 145.02, 127.57, 121.40, 114.84, 111.23, 76.73, 56.02, 33.29.


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1,3-Dimethoxy-2-(2-nitroethyl)benzene (10)

Prepared according a reported procedure.[20] The crude mixture was purified by column chromatography on silica gel, eluting with hexane/EtOAc 8:2 to afford the title product as a pale-yellow oil (85% yield).

1H NMR (300 MHz, CDCl3): δ = 7.21 (t, J = 8.4 Hz, 1 H), 6.56 (d, J = 8.4 Hz, 2 H), 4.51–4.46 (m, 2 H), 3.83 (s, 6 H), 3.43–3.38 (m, 2 H).

13C NMR (75 MHz, CDCl3): δ = 158.54, 128.63, 111.82, 103.66, 74.05, 55.74, 21.69.

MS(EI+): m/z calcd. for C10H13NO4: 211.084458; found: 211.084720.


#

5-(2-Nitroethyl)benzo[1,3]dioxole (11)

The crude mixture was purified by column chromatography on silica gel, eluting with hexane/EtOAc 9:1 to afford the title product as a yellow oil (58 % yield). All analytical data are in agreement with the literature.[17]

1H NMR (300 MHz, CDCl3): δ = 6.75 (d, J = 7.8 Hz, 1 H), 6.68–6.63 (m, 2 H), 5.93 (s, 2 H), 4.55 (t, J = 7.3 Hz, 2 H), 3.22 (t, J = 7.3 Hz, 2 H).

13C NMR (75 MHz, CDCl3): δ = 148.15, 147.03, 129.36, 121.82, 109.00, 108.73, 101.25, 76.63, 33.31.


#

1-(4-Fluorophenyl)-2-nitroethane (12)

The crude mixture was purified by column chromatography on silica gel, eluting with hexane/EtOAc 9:1 to afford the title product as a pale-yellow oil (48% yield). All analytical data are in agreement with the literature.[16]

1H NMR (300 MHz, CDCl3): δ = 7.18 (dd, J = 8.7, 5.3 Hz, 2 H), 7.01 (t, J = 8.7 Hz, 2 H), 4.59 (t, J = 7.2 Hz, 2 H), 3.29 (t, J = 7.2 Hz, 2 H).

19F NMR (282 MHz, CDCl3): δ = –115.03 (s, 1 F).

13C NMR (75 MHz, CDCl3): δ = 162.25 (d, J = 245.9 Hz), 131.52 (d, J = 3.4 Hz), 130.28 (d, J = 8.1 Hz), 115.97 (d, J = 21.5 Hz), 76.39, 32.72.


#

1-(4-Chlorophenyl)-2-nitroethane (13)

Prepared according to the general procedure (two equivalents of ammonia borane were used). The crude mixture was purified by column chromatography on silica gel, eluting with hexane/EtOAc 95:5 to afford the title product as a yellow oil (61% yield). All analytical data are in agreement with the literature.[21]

1H NMR (300 MHz, CDCl3): δ = 7.30 (d, J = 8.4 Hz, 2 H), 7.14 (d, J = 8.4 Hz, 2 H), 4.59 (t, J = 7.2 Hz, 2 H), 3.29 (t, J = 7.2 Hz, 2 H).

13C NMR (75 MHz, CDCl3): δ = 134.26, 133.52, 130.05, 129.24, 76.10, 32.81.


#

1-(4-Bromophenyl)-2-nitroethane (14)

The crude mixture was purified by column chromatography on silica gel, eluting with hexane/EtOAc 95:5 to afford the title product as a pale-yellow oil (53% yield). All analytical data are in agreement with the literature.[16]

1H NMR (300 MHz, CDCl3): δ = 7.46 (d, J = 8.4 Hz, 2 H), 7.09 (d, J = 8.4 Hz, 2 H), 4.59 (t, J = 7.2 Hz, 2 H), 3.27 (t, J = 7.2 Hz, 2 H).

13C NMR (75 MHz, CDCl3): δ = 134.77, 132.24, 130.41, 121.61, 76.03, 32.91.


#

1-Nitro-4-(2-nitroethyl)benzene (15)

Prepared according to the general procedure (two equivalents of ammonia borane were used). The crude mixture was purified by column chromatography on silica gel, eluting with hexane/EtOAc 8:2 to afford the title product as a yellow solid (44% yield). All analytical data are in agreement with the literature.[22]

1H NMR (300 MHz, CDCl3): δ = 8.18 (d, J = 8.4 Hz, 2 H), 7.40 (d, J = 8.4 Hz, 2 H), 4.68 (t, J = 7.0 Hz, 2 H), 3.43 (t, J = 7.0 Hz, 2 H).

13C NMR (75 MHz, CDCl3): δ = 147.51, 143.34, 129.68, 124.25, 75.35, 32.97.


#

2-Cyclohexyl-1-nitroethane (16)

Prepared according to the general procedure (using 1.6 mL of anhydrous methanol). The crude mixture was purified by column chromatography on silica gel, eluting with hexane/EtOAc 95:5 to afford the title product as a pale-yellow oil (85% yield). All analytical data are in agreement with the literature.[23]

1H NMR (300 MHz, CDCl3): δ = 4.39 (t, J = 7.4 Hz, 2 H), 1.89 (q, J = 7.4 Hz, 2 H), 1.76–1.59 (m, 5 H), 1.39–1.11 (m, 4 H), 1.01–0.86 (m, 2 H).

13C NMR (75 MHz, CDCl3): δ = 73.98, 35.07, 34.79, 32.85, 26.35, 26.07.


#

Nitrocyclohexane (17)

The crude mixture was purified by column chromatography on silica gel, eluting with hexane/EtOAc 98:2 to afford the title product as a colorless oil (50% yield). All analytical data are in agreement with the literature.[23]

1H NMR (300 MHz, CDCl3): δ = 4.36 (tt, J = 10.6, 4.1 Hz, 1 H), 2.30–2.16 (m, 2 H), 1.97–1.77 (m, 4 H), 1.72–1.62 (m, 1 H), 1.45–1.16 (m, 3 H).


#

4-Methyl-1-nitropentane (18)

The crude mixture was purified by column chromatography on silica gel, eluting with pentane/diethyl ether 97:3 to afford the title product as a colorless oil (53% yield). All analytical data are in agreement with the literature.[24]

1H NMR (300 MHz, CDCl3): δ = 4.34 (t, J = 7.1 Hz, 2 H), 2.09–1.91 (m, 2 H), 1.58 (dp, J = 13.3, 6.6 Hz, 1 H), 1.27–1.19 (m, 2 H), 0.89 (d, J = 6.6 Hz, 6 H).


#

1-Nitro-4-phenylbutane (19)

Prepared according to the general procedure (using 1.6 mL of anhydrous methanol). The crude mixture was purified by column chromatography on silica gel, eluting with hexane/EtOAc 9:1 to afford the title product as a colorless oil (55% yield). All analytical data are in agreement with the literature.[25]

1H NMR (300 MHz, CDCl3): δ = 7.33–7.17 (m, 5 H), 4.38 (t, J = 7.0 Hz, 2 H), 2.69 (t, J = 7.5 Hz, 2 H), 2.04 (quint, J = 7.2 Hz, 2 H), 1.74 (quint, J = 7.7 Hz, 2 H).

13C NMR (75 MHz, CDCl3): δ = 141.15, 128.61, 128.45, 126.25, 75.59, 35.10, 27.97, 26.94.


#

(E)-(4-Nitrobut-1-en-1-yl)benzene (20)

Prepared according to the general procedure (1.5 equivalents of ammonia borane were used). The crude mixture was purified by column chromatography on silica gel, eluting with hexane/EtOAc 95:5 to afford the title product as a yellow oil (63% yield). All analytical data are in agreement with the literature.[26]

1H NMR (300 MHz, CDCl3): δ = 7.38–7.21 (m, 5 H), 6.53 (dt, J = 15.8, 1.5 Hz, 1 H), 6.12 (dt, J = 15.8, 7.0 Hz, 1 H), 4.50 (t, J = 7.0 Hz, 2 H), 2.90 (qd, J = 7.0, 1.4 Hz, 2 H).

13C NMR (75 MHz, CDCl3): δ = 136.60, 134.12, 128.72, 127.91, 126.39, 123.06, 75.08, 30.85.


#

1-Nitro-2-phenylpropane (21)

Prepared according to the general procedure (three equivalents of ammonia borane were used and the reaction was stirred for 6 hours). The crude mixture was purified by column chromatography on silica gel, eluting with hexane/EtOAc 95:5 to afford the title product as a yellow oil (66% yield). All analytical data are in agreement with the literature.[27]

1H NMR (300 MHz, CDCl3): δ = 7.37–7.22 (m, 5 H), 4.52 (qd, J = 12.0, 7.8 Hz, 2 H), 3.64 (h, J = 7.2 Hz, 1 H), 1.39 (d, J = 7.0 Hz, 3 H).

13C NMR (75 MHz, CDCl3): δ = 141.04, 129.09, 127.68, 127.03, 81.98, 38.77, 18.85.


#

2-Nitro-1-phenylpropane (22)

Prepared according to the general procedure (using 1.6 mL of anhydrous methanol). The crude mixture was purified by column chromatography on silica gel, eluting with hexane/EtOAc 95:5 to afford the title product as a pale-yellow oil (80% yield). All analytical data are in agreement with the literature.[19]

1H NMR (300 MHz, CDCl3): δ = 7.30 (dd, J = 9.8, 7.0 Hz, 3 H), 7.18 (d, J = 6.6 Hz, 2 H), 4.79 (h, J = 6.8 Hz, 1 H), 3.33 (dd, J = 14.0, 7.5 Hz, 1 H), 3.02 (dd, J = 14.0, 6.8 Hz, 1 H), 1.55 (d, J = 6.7 Hz, 3 H).

13C NMR (75 MHz, CDCl3): δ = 135.66, 129.11, 128.95, 127.54, 84.55, 41.30, 18.92.


#
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Supporting Information

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    • 5b Boom DH. A, Jupp AR, Slootweg JC. Chem. Eur. J. 2019; 25: 9133
    • 5c Melen RL. Chem. Soc. Rev. 2016; 45: 775
  • 6 Yang X, Fox T, Berke H. Chem. Commun. 2011; 47: 2053
  • 7 Chong CC, Rao B, Kinjo K. ACS Catal. 2017; 7: 5814
  • 8 The formation of the dimer 3a,b is due to the attack of a molecule of reduced nitroalkane on to a molecule of unreacted nitroalkene still present in solution. The two diastereoisomers are always formed as a 1:1 mixture.
  • 9 After chromatographic purification, the product was isolated in 63% yield; unreacted starting material (10%), the dimeric adduct (18%) and unidentified decomposition products were also obtained.
  • 10 Preliminary studies using (thio)urea derivatives of cinchona alkaloid derivatives afforded product 21 in good yields and up to 21% e.e. Further studies and the use of new, ‘ad hoc’ designed chiral catalysts are necessary to improve the enantioselectivity of the process, and studies are under way in our group.
  • 11 Yang X, Fox T, Berke H. Org. Biomol. Chem. 2012; 10: 852
  • 12 When the reduction to produce 2 and 22 was performed in CD3OD, in both cases the formation of the α,α-bisdeuterated nitroalkane was detected (see NMR spectra in the Supporting Information). However, these preliminary studies with deuterated solvents or reagents were not conclusive; the use of a protic solvent, such as methanol, and the acidity of the protons in a position of the nitroalkane make possible different scenarios for the protonation step and more carefully designed studies are needed to clarify the mechanistic details.
  • 13 Vojáčková P, Chalupa D, Prieboj J, Nečas J, Švenda J. Org. Lett. 2018; 20: 7085
  • 14 Dong X, Teng H, Wang C. Org. Lett. 2009; 11: 1265
  • 15 Marčeková M, Gerža P, Šoral M, Moncol J, Berkeš D, Kolarovič A, Jakubec P. Org. Lett. 2019; 21: 4580
  • 16 Mahesh S, Adebomi V, Muneeswaran ZP, Raj M. Angew. Chem. Int. Ed. 2020; 59: 2793
  • 17 Rezazadeh S, Devannah V, Watson DA. J. Am. Chem. Soc. 2017; 139: 8110
  • 18 Cai S, Zhang S, Zhao Y, Wang DZ. Org. Lett. 2013; 15: 2660
  • 19 Xianga J, Sunb E, Liana C, Yuana W, Zhua J, Wanga Q, Deng J. Tetrahedron 2012; 68: 4609
  • 20 Wangand J, Evano G. Org. Lett. 2016; 18: 3542
  • 21 McNamara YM, Cloonan SM, Knox AJ. S, Keating JJ, Butler SG, Peters GH, Meegan MJ, Williams DC. Bioorg. Med. Chem. 2011; 19: 1328
  • 22 Cai S, Zhao X, Wang X, Liu Q, Li Z, Wang DZ. Angew. Chem. Int. Ed. 2012; 51: 8050
  • 23 Zhang Z, Schreiner PR. Synthesis 2007; 2559
  • 24 Chandrasekhar S, Shrinidhi A. Synth. Commun. 2014; 44: 3008
  • 25 Matsubara R, Kim H, Sakaguchi T, Xie W, Zhao X, Nagoshi Y, Wang C, Tateiwa M, Ando A, Hayashi M, Yamanaka MTsuneda T. Org. Lett. 2020; 22: 1182
  • 26 Padilla-Salinas R, Walvoord RR, Tcyrulnikov S, Kozlowski MC. Org. Lett. 2013; 15: 3966
  • 27 Hostmann T, Molloy JJ, Bussmann K, Gilmour R. Org. Lett. 2019; 21: 10164

Corresponding Author

Maurizio Benaglia
Dipartimento di Chimica, Università degli Studi di Milano
Via Golgi, 19, 20133 Milano
Italy   

Publication History

Received: 21 September 2020

Accepted after revision: 09 October 2020

Publication Date:
25 November 2020 (online)

© 2020. This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial-License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/)

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  • References

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    • 5c Melen RL. Chem. Soc. Rev. 2016; 45: 775
  • 6 Yang X, Fox T, Berke H. Chem. Commun. 2011; 47: 2053
  • 7 Chong CC, Rao B, Kinjo K. ACS Catal. 2017; 7: 5814
  • 8 The formation of the dimer 3a,b is due to the attack of a molecule of reduced nitroalkane on to a molecule of unreacted nitroalkene still present in solution. The two diastereoisomers are always formed as a 1:1 mixture.
  • 9 After chromatographic purification, the product was isolated in 63% yield; unreacted starting material (10%), the dimeric adduct (18%) and unidentified decomposition products were also obtained.
  • 10 Preliminary studies using (thio)urea derivatives of cinchona alkaloid derivatives afforded product 21 in good yields and up to 21% e.e. Further studies and the use of new, ‘ad hoc’ designed chiral catalysts are necessary to improve the enantioselectivity of the process, and studies are under way in our group.
  • 11 Yang X, Fox T, Berke H. Org. Biomol. Chem. 2012; 10: 852
  • 12 When the reduction to produce 2 and 22 was performed in CD3OD, in both cases the formation of the α,α-bisdeuterated nitroalkane was detected (see NMR spectra in the Supporting Information). However, these preliminary studies with deuterated solvents or reagents were not conclusive; the use of a protic solvent, such as methanol, and the acidity of the protons in a position of the nitroalkane make possible different scenarios for the protonation step and more carefully designed studies are needed to clarify the mechanistic details.
  • 13 Vojáčková P, Chalupa D, Prieboj J, Nečas J, Švenda J. Org. Lett. 2018; 20: 7085
  • 14 Dong X, Teng H, Wang C. Org. Lett. 2009; 11: 1265
  • 15 Marčeková M, Gerža P, Šoral M, Moncol J, Berkeš D, Kolarovič A, Jakubec P. Org. Lett. 2019; 21: 4580
  • 16 Mahesh S, Adebomi V, Muneeswaran ZP, Raj M. Angew. Chem. Int. Ed. 2020; 59: 2793
  • 17 Rezazadeh S, Devannah V, Watson DA. J. Am. Chem. Soc. 2017; 139: 8110
  • 18 Cai S, Zhang S, Zhao Y, Wang DZ. Org. Lett. 2013; 15: 2660
  • 19 Xianga J, Sunb E, Liana C, Yuana W, Zhua J, Wanga Q, Deng J. Tetrahedron 2012; 68: 4609
  • 20 Wangand J, Evano G. Org. Lett. 2016; 18: 3542
  • 21 McNamara YM, Cloonan SM, Knox AJ. S, Keating JJ, Butler SG, Peters GH, Meegan MJ, Williams DC. Bioorg. Med. Chem. 2011; 19: 1328
  • 22 Cai S, Zhao X, Wang X, Liu Q, Li Z, Wang DZ. Angew. Chem. Int. Ed. 2012; 51: 8050
  • 23 Zhang Z, Schreiner PR. Synthesis 2007; 2559
  • 24 Chandrasekhar S, Shrinidhi A. Synth. Commun. 2014; 44: 3008
  • 25 Matsubara R, Kim H, Sakaguchi T, Xie W, Zhao X, Nagoshi Y, Wang C, Tateiwa M, Ando A, Hayashi M, Yamanaka MTsuneda T. Org. Lett. 2020; 22: 1182
  • 26 Padilla-Salinas R, Walvoord RR, Tcyrulnikov S, Kozlowski MC. Org. Lett. 2013; 15: 3966
  • 27 Hostmann T, Molloy JJ, Bussmann K, Gilmour R. Org. Lett. 2019; 21: 10164

Zoom Image
Scheme 1 Chemoselective AB-mediated reduction of nitroalkenes
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Scheme 2 AB-mediated reduction of β-nitrostyrene
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Scheme 3 AB-mediated reduction of functionalized β-nitrostyrenes
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Scheme 4 AB-mediated reduction of β-nitroalkenes
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Scheme 5 Proposed mechanism for the AB-mediated reduction of β-nitroalkenes