Phosphinoyl-aziridines as a new class of chiral catalysts for enantioselective Michael addition

Tetrahedron 75 (2019) 230e235

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Phosphinoyl-aziridines as a new class of chiral catalysts for enantioselective Michael addition Zuzanna Wujkowska, Anna Zawisza, Stanisław Le
sniak, Michał Rachwalski*
d
z, Tamka 12, 91-403 Ło
d
z, Poland Department of Organic and Applied Chemistry, University of Ło

a r t i c l e i n f o

a b s t r a c t

Article history: Received 6 September 2018 Received in revised form 22 November 2018 Accepted 24 November 2018 Available online 28 November 2018

A series of new optically pure phosphine oxides containing chiral aziridine subunit were synthesized in good yields and applied as organocatalysts in asymmetric Michael reaction of various aliphatic aldehydes with b-nitrostyrene. The corresponding organocatalysts were synthesized starting from optically pure aziridines in a few simple efficient steps. The appropriate Michael adducts were obtained in most cases in very high chemical yield (up to 97%), excellent enantioselectivity (up to 98% of ee) and diastereoselectivity (up to 95:5 of dr). © 2018 Elsevier Ltd. All rights reserved.

Keywords: Asymmetric synthesis Aziridines Chiral catalysts Michael addition Organocatalysis

1. Introduction Enantioselective construction of new carbon-carbon bonds using organocatalytic approaches is still one of the most important fields in modern synthetic organic chemistry [1e3]. The optical purity is the most important for the chiral substances being of particular interest for pharmaceutical or food industry. The choice of the appropriate chiral catalyst for any asymmetric transformation is crucial for the chemical yield and enantioselectivity of desired stereocontrolled process. Asymmetric Michael addition reaction constitutes one of the most powerful tools for generation of various valuable building blocks [4], and for the synthesis of natural products like e.g. strychnine, quinine, quinidine and other [5].Among a large variety of chiral organocatalysts, amines and their derivatives proved to be the most active systems, which can efficiently catalyze asymmetric Michael reaction. Typical examples of such catalysts are derivatives of proline, which were applied in the reaction of acetaldehyde and cyclohexanone with b-nitrostyrene [6,7], thiourea systems [8,9], primary amines and their salts [10,11], imines [12], and other [13e15]. Chiral phosphines and phosphine oxides bearing an aziridine ring are not explored extensively in chemical literature. There are

* Corresponding author. E-mail address: [email protected] (M. Rachwalski). https://doi.org/10.1016/j.tet.2018.11.052 0040-4020/© 2018 Elsevier Ltd. All rights reserved.

only a few examples describing the application of such phosphines in the enantioselective diethylzinc addition to imines [16], and the use of chiral phosphine oxides in the enantioselective direct aldol reactions [17], 1,3-dipolar cycloaddition [18], Abramov-type phosphonylation of aldehydes [19], and in the enantioselective allylsilane addition to aldehydes [20]. On the basis of our experience in the field of asymmetric synthesis in the presence of various heteroorganic chiral catalysts [21e25], and taking all the aforementioned circumstances into account, we decided to synthesize a series of chiral phosphine oxides bearing an aziridine subunit and to check their catalytic activity in asymmetric Michael addition of aliphatic aldehydes to bnitrostyrene. 2. Results and discussion 2.1. Synthesis of the chiral phosphine oxides L1-L5 Five chiral phosphine oxides L1-L5 (Fig. 1) were synthesized through a five-step synthetic pathway (Scheme 1). In the first step, 2-(diphenylphosphino)benzoic acid 1 was reduced with lithium aluminum hydride in boiling THF giving 2(diphenylphosphino)benzyl alcohol 2 in quantitative yield [26]. Next, phosphine 2 was oxidized with 10% hydrogen peroxide in acetone to phosphine oxide 3 in quantitative yield [26]. Then, primary alcohol 3 was converted to the corresponding bromide 4 (95%

Z. Wujkowska et al. / Tetrahedron 75 (2019) 230e235

231

Fig. 1. Chiral phosphine oxides L1-L5 bearing an aziridine subunit.

Scheme 1. Synthesis of chiral phosphine oxides L1-L5.

yield) using phosphorus tribromide in the mixture of THF and DCM according to literature protocol [27]. Finally, bromide 4 was treated with a series of enantiomerically pure aziridines 5 in the presence of potassium carbonate in DMF giving catalysts L1-L5 in yields from 73 to 87%. 2.2. Asymmetric Michael addition in the presence of catalysts L1-L5

Table 1 Asymmetric Michael addition in the presence of catalysts L1-L5. Entry

Catalyst

Yield [%]

ee [%]a

drb

Abs. conf.c

1 2 3 4 5

L1 L2 L3 L4 L5

42 57 62 54 52

40 54 58 49 47

55:45 60:40 60:40 60:40 60:40

(2R,3S) (2S,3R) (2R,3S) (2R,3S) (2R,3S)

a

The catalytic activity of systems L1-L5 was checked in asymmetric Michael addition of b-nitrostyrene to propanal in DCM at room temperature following a literature protocol (Scheme 2) [13]. The results are summarized in Table 1. All the results clearly demonstrate that compounds L1-L5 exhibited only moderate catalytic activity, leading to the desired product in chemical yields and enantioselectivities around 50%. It should be also noted that the use of catalysts L2 and L3 having opposite absolute configurations at stereogenic carbon atom located in the aziridine ring, led to the formation of addition products also with opposite configurations (Table 1, entries 2 and 3). 2.3. Synthesis of the chiral phosphine oxides L6-L9

b c

Determined by chiral HPLC. Determined from 1H NMR. According to literature data (for major product) [13].

reduce rigidity of transition state leading to the lowering of stereoselectivity. The synthetic route leading to systems L6-L9 comprises two steps (Scheme 3). In the first one, o-bromoanisole 11 was reacted with diphenylphosphinic chloride 12 in the presence of magnesium turnings and catalytic amount of iodine in THF to form the corresponding phosphine oxide 13 in 80% yield [28]. Finally, compound 13 was treated with a series of enantiomerically pure aziridines 5 in the presence of n-butyllithium solution to form the corresponding catalysts L6-L9 in yields from 70 to 75% [29]. To the best of our knowledge, this is one of the first examples of direct arylation on

In the light of these some unsatisfactory results, we decided to synthesize a series of analogous derivatives L6-L9 without a methylene group between phenyl ring and aziridinyl nitrogen atom (Fig. 2). In our opinion, methylene group in the studied catalyst may

Scheme 2. Asymmetric Michael addition in the presence of catalysts L1-L5.

N

N

N

N

PPh2 O L6

PPh2 O L7

PPh2 O L8

PPh2 O L9

Fig. 2. Chiral phosphine oxides L6-L9 bearing an aziridine subunit.

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R OCH3 + Br 11

OCH3

Mg, I2 ClPPh2 THF, reflux O 12

75%

13

PPh2 O

R

N H 5

N

n-BuLi, THF -80oC to rt

PPh2 O

14: R = ( R)-CH(CH3)2, (L6) (71%) 15: R = ( S)-CH(CH3)2, (L7) (59%) 16: R = ( S)-CH2CH(CH3) 2, (L8) (57%) 17: R = ( S)-C6H5, (L9) (67%) Scheme 3. Synthesis of chiral phosphine oxides L6-L9.

the nitrogen atom of aziridines using nucleophilic substitution reaction. 2.4. Asymmetric Michael addition in the presence of catalysts L6-L9 As previously, a catalytic activity of newly obtained derivatives L6-L9 was checked in asymmetric Michael reaction of propanal and b-nitrostyrene (Scheme 4) [13]. The results are collected in Table 2. Inspection of Table 2 reveals that all the catalysts L6-L9 exhibited high activity in the model reaction, leading to the desired chiral product in good chemical yield and with high enantio- and diastereoselectivity. Moreover, as in previous studies, the use of systems L6 and L7 bearing opposite configurations at the aziridinyl stereogenic centre, led to the formation of opposite enantiomers of product. This may indicate that stereogenic centre located at aziridine subunit has a decisive influence on the stereochemical outcome of the title reaction. Having the most active catalytic system L7 in hand, we decided to extend a scope of substrates to another aliphatic aldehydes under analogous conditions (Scheme 5) [13]. The results are listed in Table 3. All the results clearly show that chiral phosphine oxide L7 is prone to efficiently catalyze a Michael addition of b-nitrostyrene to various aliphatic aldehydes leading to the desired chiral adducts in very good yields and with excellent enantio- and diastereoselectivity. From these results, we propose the plausible transition-state model, which reasonably explains the relative (syn) and absolute configuration of the obtained Michael adducts (Fig. 3). The newly designed catalysts L1-L9 comprise a chiral aziridine unit covalently adhered to a phosphine oxide moiety creating the dual activation model according to which, the two substrates involved in the reaction are activated simultaneously by catalyst. In order to test the efficacy of the above-mentioned catalyst, nitroolefins were chosen as Michael acceptors due to the polar nitro group and aliphatic aldehydes as a donor. The nitrogen atom of the aziridine ring first deprotonates an acidic proton of aldehyde generating the complex A. Assuming the trans configuration of the iso-propyl at C-2 of the ring and aryl substituent at N-1, and R-configuration on C-2 of aziridine it can be noticed that only Si-face of the enolate can act as Michael donor (the Re-face is crowded by the isopropyl group of aziridine) (complex A, Fig. 3). At this point, the crucial aspect of the stereochemical pathway of the reaction is the orientation of nitrostyrene in transition state, and more precisely, factors

Table 2 Asymmetric Michael addition in the presence of catalysts L6-L9. Entry

Catalyst

Yield [%]

ee [%]a

drb

Abs. conf.c

1 2 3 4

L6 L7 L8 L9

90 91 85 82

84 91 75 82

81:15 90:10 80:20 75:25

(2S,3R) (2R,3S) (2R,3S) (2R,3S)

a b c

Determined by chiral HPLC. Determined from 1H NMR. According to literature data (for major product) [13].

determining this orientation. Although the reasons for the high enantioselectivity are not clarified decisively at this stage, we assumed the dipole interactions of nitroolefin with the P-oxide group as well as the formed hydrogen bonds are important factors in controlling the stereochemistry. It is known that chiral catalysts based on phosphine oxides used as Lewis bases play important role in organocatalytic stereoselective reactions. However, in all of these reactions chlorosilanes derivatives are used as co-reagents. Tetra-coordinated silicon compounds and chiral Lewis bases can form five- or sixcoordinate hypervalent silicon species in situ and promote catalytic enantioselective reaction in good yields and enantioselectivities [17e20,30e33]. No chlorosilane derivatives have been used in our study, therefore, any models containing hypervalent silicate derivatives are useless. On the other hand, Zhong et al. described a highly stereoselective Michael addition to nitroolefines catalyzed by the systems which comprise chiral pyrrolidine unit adhered to phosphine oxide moiety [34]. In their conviction, the strong polar P]O group may interact with nitro group via dipole (ion) interactions (O
d ¼ Pþd)
dO2Nþd-). Based on above, we propose that the aziridine ring will first react with an aldehyde to give an enolate positioned as described above. Then, strong H-bonds between NH and O (enolate) and O (nitro group) orientate nitroolefine, so that, the enolate may attack the double bond of nitroolefine from Re-face to form syn Michael adduct (S, R) (Fig. 3, B) and also avoiding steric repulsion between phenyl group of nitrostyrene and phenyl group of phosphine oxide. Such orientation of nitroolefine can be furthermore stabilized by dipole-dipole (ion-ion) interactions of negative polarized oxygen atoms (from enolate and nitro group) with positive polarized phosphorus (polar P]O) and nitrogen atoms (NO2) as indicated on Fig. 3. Other conformation of nitrostyrene (attack from Si-face) This proposition is consistent with the experimental results. 3. Conclusions

Scheme 4. Asymmetric Michael addition in the presence of catalysts L6-L9.

The newly synthesized phosphine oxides bearing a chiral aziridine subunit have proven to be effective systems catalyzing asymmetric Michael addition of b-nitrostyrene to various aliphatic

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233

Scheme 5. Asymmetric Michael addition in the presence of catalyst L7.

as yellow oil was prepared according to literature [26] in quantitative yield. The spectroscopic data are in accordance with literature [26].

Table 3 Asymmetric Michael addition in the presence of catalyst L7. Entry

Aldehyde

Yield [%]

ee [%]a

drb

1 2 3 4 5

a b c d e

95 97 97 94 95

98 75 97 91 95

95:5 n.a.c 95:5 95:5 95:5

a b c

Determined by chiral HPLC. Determined from 1H NMR. Not applicable.

4.3. 2-(Diphenylphosphinoyl)benzyl alcohol (3) The synthesis and spectroscopic data for 2-(diphenylphosphinoyl)benzyl alcohol (3) are in accordance to literature [26]. Colorless solid, 100% yield; m.p. 162.7e164.3  C; Lit [26]. m.p. 163e164  C. 4.4. 2-(Diphenylphosphinoyl)benzyl bromide (4)

aldehydes leading to desired chiral adducts in good chemical yield and with high enantio- and diastereoselectivity. Moreover, each enantiomer of the desired product may be accessed by the application of the respective enantiomeric catalysts.

The synthesis and spectroscopic data for 2-(diphenylphosphinoyl)benzyl bromide (4) are in accordance to literature [27]. Colorless waxy solid, 95% yield; m.p. 116.7e118.5  C; Lit [28]. m.p. 118e120  C.

4. Experimental

4.5. General procedure of the synthesis of catalysts L1-L5

4.1. General

In a Schlenk tube, benzyl bromide 4 (0.56 g, 1.5 mmol), K2CO3 (0.83 g, 6 mmol) and dry DMF (3 mL) were mixed at 0  C. The mixture was stirred for 15 min under argon followed by the addition of appropriate aziridine 5 (1.5 mmol) dissolved in 2 mL of DMF. The ice bath was removed after the addition and the resulting solution was allowed to stir at room temperature for 12 h. Water (5 mL) was added in order to quench the reaction, which was extracted with Et2O (3  10 mL) and the combined organic layers were dried over anhydrous MgSO4, filtered and the solvents were evaporated in vacuo. The crude mixture was purified by column chromatography (silica gel, hexane/ethyl acetate/methanol, 3: 3: 0.5).

Tetrahydrofurane was distilled from sodium benzophenone ketyl radical. Dichloromethane was distilled over calcium chloride. 1 H, 13C and 31P NMR spectra were recorded on a Bruker instrument at 600 MHz and 150 MHz, respectively, with CDCl3 as solvent and TMS as internal standard. Data are reported as s ¼ singlet, d ¼ doublet, t ¼ triplet, q ¼ quartet, m ¼ multiplet, br. s ¼ broad singlet. Optical rotations were measured on a Anton Paar MCP500 polarimeter with a sodium lamp at room temperature (c 0.5). Column chromatography was performed using Merck 60 silica gel. TLC was performed on Merck 60 F254 silica gel plates. Visualization was accomplished with UV light (254 nm) or using iodine vapors. The enantiomeric excess (ee) values were determined by chiral HPLC (Chiralcel AD-H column). 4.2. 2-(Diphenylphosphino)benzyl alcohol (2) The analytically pure 2-(diphenylphosphino)benzyl alcohol (2)

4.5.1. (2S)-1-[2-(diphenylphosphinoyl)benzyl]-2-methylaziridine (L1) Slightly yellow oil (0.41 g, 79%); þ12.36 (c 0.5, CHCl3); 1H NMR (600 MHz, CDCl3): d ¼ 1.17 (d, 3H, J ¼ 5.5 Hz, CH3), 1.24 (d, 1H, J ¼ 6.4 Hz, CHN), 1.33e1.38 (m, 1H, CHN), 1.50 (d, 1H, J ¼ 3.5 Hz, CHN), 3.75 (d, 1H, J ¼ 16.3 Hz, CH2C6H4), 3.79 (d, 1H, J ¼ 16.3 Hz,

Fig. 3. Possible transition state model.

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CH2C6H4), 7.00 (dd, 1H, J ¼ 14.2, 7.6 Hz, Har), 7.19 (t, 1H, J ¼ 7.3 Hz, Har), 7.43e7.50 (m, 4H, Har), 7.52e7.58 (m, 3H, Har), 7.58e7.65 (m, 4H, Har), 8.02e8.05 (m, 1H, Har) ppm; 13C NMR (150 MHz, CDCl3): d ¼ 18.3 (CH3), 29.8 (CHN), 35.0 (CHN), 61.9 (d, J ¼ 4.9 Hz, CH2C6H4), 125.9 (d, J ¼ 13.0 Hz, Car), 128.6 (d, J ¼ 1.8 Hz, 2Car), 128.7 (d, J ¼ 1.5 Hz, 2Car), 128.8, 129.1, 129.8 (Car), 131.9 (d, J ¼ 2.4 Hz, Car), 132.0 (d, J ¼ 3.7 Hz, 2Car), 132.1 (d, J ¼ 4.1 Hz, Car), 132.4 (d, J ¼ 2.6 Hz, Car), 132.6, 133.1, 133.2, 133.3 (Car), 145.7 (d, J ¼ 7.3 Hz, Car) ppm; 31P NMR (243 MHz, CDCl3): d ¼ 31.75 ppm; Anal. calcd. for C22H22NOP: C 76.06, H 6.38, N 4.03; found: C 76.03, H 6.62, N 3.77. 4.5.2. (2R)-1-[2-(diphenylphosphinoyl)benzyl]-2isopropylaziridine (L2) Slightly yellow oil (0.41 g, 73%); -16.36 (c 0.5, CHCl3); 1H NMR (600 MHz, CDCl3): d ¼ 0.82 (d, 3H, J ¼ 6.8 Hz, CH3), 0.86 (d, 3H, J ¼ 6.8 Hz, CH3), 1.05e1.11 (m, 1H, CH(CH3)2, 1.15 (d, 1H, J ¼ 6.4 Hz, CHN), 1.21e1.28 (m, 1H, CHN), 1.55 (d, 1H, J ¼ 3.5 Hz, CHN), 3.62 (d, 1H, J ¼ 15.7 Hz, CH2C6H4), 3.89 (d, 1H, J ¼ 15.7 Hz, CH2C6H4), 7.00 (dd, 1H, J ¼ 14.2, 7.6 Hz, Har), 7.19 (t, 1H, J ¼ 7.4 Hz, Har), 7.43e7.50 (m, 4H, Har), 7.53e7.58 (m, 3H, Har), 7.58e7.63 (m, 4H, Har), 8.05e8.10 (m, 1H, Har) ppm; 13C NMR (150 MHz, CDCl3): d ¼ 19.4 (CH3), 20.5 (CH3), 31.3 (CHN), 33.0 (CHN), 46.4 (CH(CH3)2, 61.0 (d, J ¼ 5.0 Hz, CH2C6H4), 125.8 (d, J ¼ 12.6 Hz, Car), 128.5 (d, J ¼ 12.0 Hz, 4Car), 129.2 (Car), 129.5 (d, J ¼ 10.0 Hz, Car), 129.9 (Car), 131.8 (d, J ¼ 2.1 Hz, Car), 131.9 (d, J ¼ 9.7 Hz, 4Car), 132.1 (d, J ¼ 2.1 Hz, Car), 132.6 (d, J ¼ 9.4 Hz, Car), 133.0 (d, J ¼ 12.5 Hz, Car), 133.3 (d, J ¼ 9.0 Hz, Car), 145.6 (d, J ¼ 7.6 Hz, Car) ppm; 31P NMR (243 MHz, CDCl3): d ¼ 31.62 ppm; Anal. calcd. for C24H26NOP: C 76.78, H 6.98, N 3.73; found: C 77.67, H 7.27, N 3.57. 4.5.3. (2S)-1-[2-(diphenylphosphinoyl)benzyl]-2-isopropylaziridine (L3) Slightly yellow oil (0.49 g, 87%); þ20.22 (c 0.5, CHCl3); 1H NMR (600 MHz, CDCl3): d ¼ 0.81 (d, 3H, J ¼ 6.8 Hz, CH3), 0.84 (d, 3H, J ¼ 6.8 Hz, CH3), 1.02e1.08 (m, 1H, CH(CH3)2, 1.14 (d, 1H, J ¼ 6.4 Hz, CHN), 1.18e1.26 (m, 1H, CHN), 1.54 (d, 1H, J ¼ 3.5 Hz, CHN), 3.60 (d, 1H, J ¼ 15.7 Hz, CH2C6H4), 3.87 (d, 1H, J ¼ 15.7 Hz, CH2C6H4), 6.98 (dd, 1H, J ¼ 14.2, 7.6 Hz, Har), 7.17 (t, 1H, J ¼ 6.8 Hz, Har), 7.42e7.48 (m, 4H, HAr), 7.52e7.57 (m, 3H, Har), 7.57e7.63 (m, 4H, Har), 8.03e8.07 (m, 1H, Har) ppm; 13C NMR (150 MHz, CDCl3): d ¼ 19.5 (CH3), 20.6 (CH3), 31.4 (CHN), 33.2 (CHN), 46.5 (CH(CH3)2), 62.1 (d, J ¼ 4.6 Hz, CH2C6H4), 126.0 (d, J ¼ 13.0 Hz, Car), 128.6 (d, J ¼ 1.9 Hz, 2Car), 128.7 (d, J ¼ 1.9 Hz, 2Car), 129.4 (Car), 129.6 (d, J ¼ 9.9 Hz, Car), 130.0 (Car), 131.9 (d, J ¼ 2.5 Hz, Car), 132.1 (d, J ¼ 9.7 Hz, 4Car), 132.2 (d, J ¼ 2.7 Hz, Car), 132.8 (d, J ¼ 9.2 Hz, Car), 133.1 (d, J ¼ 13.0 Hz, Car), 133.4 (d, J ¼ 9.0 Hz, Car), 145.8 (d, J ¼ 7.6 Hz, Car) ppm; 31P NMR (243 MHz, CDCl3): d ¼ 31.64 ppm; Anal. calcd. for C24H26NOP: C 76.78, H 6.98, N 3.73; found: C 76.79, H 6.97, N 3.45. 4.5.4. (2S)-1-[2-(diphenylphosphinoyl)benzyl]-2-isobutylaziridine (L4) Slightly yellow oil (0.49 g, 87%); þ26.60 (c 0.5, CHCl3); 1H NMR (600 MHz, CDCl3): d ¼ 0.84 (d, 3H, J ¼ 6.7 Hz, CH3), 0.86 (d, 3H, J ¼ 6.7 Hz, CH3), 1.07e1.17 (m, 1H, CH(CH3)2, 1.24 (d, 1H, J ¼ 6.2 Hz, CHN), 1.33e1.40 (m, 1H, CHN), 1.40e1.46 (m, 1H, CH2CH(CH3)2), 1.51 (d, 1H, J ¼ 2.6 Hz, CHN), 1.59e1.67 (m, 1H, CH2CH(CH3)2, 3.66 (d, 1H, J ¼ 16.0 Hz, CH2C6H4), 3.87 (d, 1H, J ¼ 16.0 Hz, CH2C6H4), 6.94 (dd, 1H, J ¼ 14.3, 7.7 Hz, Har), 7.19 (t, 1H, J ¼ 7.4 Hz, Har), 7.19 (m, 4H, Har), 7.43e7.50 (m, 3H, Har), 7.52e7.58 (m, 4H, Har), 7.59e7.67 (m, 4H, Har), 8.00e8.07 (m, 1H, Har) ppm; 13C NMR (150 MHz, CDCl3): d ¼ 22.5 (CH3), 23.0 (CH3), 27.2 (CH(CH3)2, 34.7 (CHN), 38.5 (CHN), 42.3 (CH2CH(CH3)2, 61.9 (d, J ¼ 4.6 Hz, CH2C6H4), 126.0 (d, J ¼ 12.6 Hz, Car), 128.6 (d, J ¼ 12,0 Hz, 4Car), 129.1 (d, J ¼ 10.3 Hz, Car), 131.9 (d, J ¼ 2.0 Hz, 2Car), 132.0 (d, J ¼ 6.1 Hz, 2Car), 132.1 (d, J ¼ 6.1 Hz, 2Car), 132.3 (d, J ¼ 2.1 Hz, Car), 132.7 (d, J ¼ 5.7 Hz, Car),

133.1 (d, J ¼ 12.9 Hz, Car), 133.4 (d, J ¼ 5.6 Hz, Car), 145.7 (d, J ¼ 7.6 Hz, Car) ppm; 31P NMR (243 MHz, CDCl3): d ¼ 31.62 ppm; Anal. calcd. for C25H28NOP: C 77.10, H 7.25, N 3.60; found: C 77.11, H 7.47, N 3.70. 4.5.5. (2S)-1-[2-(diphenylphosphinoyl)benzyl]-2-phenylaziridine (L5) Colorless solid (0.51 g, 83%); m.p. 53.6e56.3  C; þ68.51 (c 0.5, CHCl3); 1H NMR (600 MHz, CDCl3): d ¼ 1.71 (d, 1H, J ¼ 6.5 Hz, CHN), 1.87 (d, 1H, J ¼ 3.3 Hz, CHN), 2.28e2.32 (m, 1H, CHN), 3.88 (d, 1H, J ¼ 16.1 Hz, CH2C6H4), 4.04 (d, 1H, J ¼ 16.1 Hz, CH2C6H4), 6.98 (dd, 1H, J ¼ 14.3, 7.6 Hz, Har), 7.13e7.22 (m, 4H, Har), 7.24e7.28 (m, 2H, Har), 7.44e7.51 (m, 5H, Har), 7.53e7.58 (m, 2H, Har), 7.59e7.65 (m, 4H, Har), 7.95e7.99 (m, 1H, Har) ppm; 13C NMR (150 MHz, CDCl3): d ¼ 38.4 (CHN), 41.6 (CHN), 62.1 (d, J ¼ 4.7 Hz, CH2C6H4), 126.0 (d, J ¼ 12.6 Hz, Car), 126.2 (3Car), 126.9, 128.4 (2Car), 128.7 (d, J ¼ 2.8 Hz, 2Car), 128.8 (d, J ¼ 2.9 Hz, 2Car), 129.2 (d, J ¼ 9.3 Hz, Car), 129.9 (Car), 132.0 (d, J ¼ 2.3 Hz, 2Car), 132.1 (d, J ¼ 9.5 Hz, 4Car), 132.5 (Car), 132.7 (d, J ¼ 14.8 Hz, Car), 133.2 (d, J ¼ 12.4 Hz, Car), 133.4 (d, J ¼ 14.7 Hz, Car), 140.5 (Car), 145.3 (d, J ¼ 7.4 Hz, Car) ppm; 31P NMR (243 MHz, CDCl3): d ¼ 31.62 ppm; Anal. calcd. for C27H24NOP: C 79.20, H 5.91, N 3.42; found: C 79.14, H 5.97, N 3.14. 4.6. Diphenyl(2-methoxyphenyl)phosphine oxide (13) The synthesis was performed according to literature [29]. Spectroscopic data are in accordance with literature [35]. Yellowish solid, 75% yield; m.p. 164e165.2  C; Lit [35]. m.p. 164.2e166.6  C. 4.7. General procedure of the synthesis of catalysts L6-L9 Compounds L6-L9 were prepared according literature protocol [36]. To the solution of the corresponding aziridine 5 (1.50 mmol) in anhydrous THF (2 mL) was added dropwise n-BuLi (0.82 mL, 1.6 mmol, 1.95 M solution in hexane) at
79  C under argon. The mixture was stirred at room temperature for 2 h under argon and phosphine oxide 13 (0.456 g, 1.48 mmol) was added at 0  C. The stirring was continued overnight at room temperature. Next, the mixture was diluted with ether and quenched with saturated aqueous solution of ammonium chloride. The organic phase was washed with brine, dried over anhydrous MgSO4 and concentrated in vacuo. The residue was purified via column chromatography (silica gel, hexane/ethyl acetate/methanol 3:3:0.25) to afford the catalysts L6-L9. 4.7.1. (2R)-1-[2-(diphenylphosphinoyl)phenyl]-2-isopropylaziridine (L6) Yellowish oil (0.51 g, 71%); -9.60 (c 0.5, CHCl3); 1H NMR (600 MHz, CDCl3): d ¼ 0.69 (d, 3H, J ¼ 6.8 Hz, CH3), 0.85 (d, 3H, J ¼ 6.8 Hz, CH3), 1.57e1.61 (m, 1H, CHN), 1.81 (d, 1H, J ¼ 3.7 Hz, CHN), 2.07 (d, 1H, J ¼ 6.8 Hz, CHN), 2.20e2.23 (m, 1H, CH(CH3)2, 6.92e6.98 (m, 2H, Har), 7.10e7.17 (m, 1H, Har), 7.39e7.51 (m, 6H, Har), 7.51e7.58 (m, 1H, Har), 7.72e7.79 (m, 2H, Har), 7.81e7.86 (m, 2H, Har) ppm; 13C NMR (150 MHz, CDCl3): d ¼ 18.3 (CH3), 19.8 (CH3), 29.6 (CHN), 36.1 (CHN), 45.7 (CH(CH3)2), 120.07 (d, J ¼ 7.7 Hz, Car), 121.5 (d, J ¼ 12.0 Hz, Car), 124.3 (Car), 124.9 (Car), 128.1 (d, J ¼ 12.0 Hz, Car), 128.3 (d, J ¼ 12.0 Hz, Car), 131.1 (d, J ¼ 3.2 Hz, Car), 131.4 (d, J ¼ 3.2 Hz, Car), 131.5 (d, J ¼ 9.8 Hz, Car), 131.6 (d, J ¼ 9.8 Hz, Car), 132.1 (d, J ¼ 9.8 Hz, Car), 133.2 (Car), 133.5 (Car), 133.7 (Car), 134.2 (Car), 134.7 (Car), 134.8 (d, J ¼ 9.8 Hz, Car), 158.1 (d, J ¼ 4.6 Hz, Car) ppm; 31P NMR (243 MHz, CDCl3): d ¼ 28.83 ppm; Anal. calcd. for C23H24NOP: C 76.45, H 6.65, N 3.88; found: C 76.57, H 6.38, N 3.78.

Z. Wujkowska et al. / Tetrahedron 75 (2019) 230e235

4.7.2. (2S)-1-[2-(diphenylphosphinoyl)phenyl]-2isopropylaziridine (L7) Yellowish oil (0.42 g, 59%); þ23.20 (c 0.5, CHCl3); 1H NMR (600 MHz, CDCl3): d ¼ 0.69 (d, 3H, J ¼ 6.8 Hz, CH3), 0.85 (d, 3H, J ¼ 6.8 Hz, CH3), 1.57e1.62 (m, 1H, CHN), 1.82 (d, 1H, J ¼ 3.7 Hz, CHN), 2.07 (d, 1H, J ¼ 6.8 Hz, CHN), 2.20e2.23 (m, 1H, CH(CH3)2, 6.92e6.98 (m, 2H, Har), 7.13e7.17 (m, 1H, Har), 7.40e7.50 (m, 6H, Har), 7.51e7.56 (m, 1H, Har), 7.75e7.79 (m, 2H, Har), 7.82e7.85 (m, 2H, Har) ppm; 13C NMR (150 MHz, CDCl3): d ¼ 18.3 (CH3), 19.8 (CH3), 29.6 (CHN), 36.1 (CHN), 45.7 (CH(CH3)2), 120.07 (d, J ¼ 7.7 Hz, Car), 121.5 (d, J ¼ 12.0 Hz, Car), 124.3 (Car), 124.9 (Car), 128.1 (d, J ¼ 12.0 Hz, Car), 128.3 (d, J ¼ 12.0 Hz, Car), 131.1 (d, J ¼ 3.2 Hz, Car), 131.4 (d, J ¼ 3.2 Hz, Car), 131.6 (d, J ¼ 9.8 Hz, Car), 132.1 (Car), 132.2 (Car), 133.2 (Car), 133.6 (Car), 133.8 (Car), 134.2 (Car), 134.5 (Car), 134.8 (d, J ¼ 9.8 Hz, Car), 158.1 (d, J ¼ 4.6 Hz, Car) ppm; 31P NMR (243 MHz, CDCl3): d ¼ 28.66 ppm; Anal. calcd. for C23H24NOP: C 76.45, H 6.65, N 3.88; found: C 76.53, H 6.32, N 3.75.

235

chemical yield, enantiomeric excess and dr values are presented in Tables 1e3. 1H and 13C NMR spectra of the Michael products are in agreement with literature [13]. Selected HPLC chromatograms of the products (racemic and enantiomeric) are presented in Supporting Information. Acknowledgement Financial support by the National Science Centre (NCN), Grant No. 2016/21/B/ST5/00421 for M. R., is gratefully acknowledged. Appendix A. Supplementary data Supplementary data to this article can be found online at https://doi.org/10.1016/j.tet.2018.11.052. References

4.7.3. (2S)-1-[2-(diphenylphosphinoyl)phenyl]-2-isobutylaziridine (L8) Yellowish oil (0.43 g, 57%); þ24.85 (c 0.5, CHCl3); 1H NMR (600 MHz, CDCl3): d ¼ 0.87 (d, 3H, J ¼ 6.7 Hz, CH3), 0.89 (d, 3H, J ¼ 6.7 Hz, CH3), 0.91e0.97 (m, 1H, CH(CH3)2, 1.49e1.54 (m, 1H, CHN), 1.60e1.67 (m, 1H, CH2CH(CH3)2), 1.76 (d, 1H, J ¼ 3.7 Hz, CHN), 2.13 (d, 1H, J ¼ 6.2 Hz, CH2CH(CH3)2, 3.33-2.37 (m, 1H), 6.94e6.96 (m, 2H, Har), 7.16e7.19 (m, 1H, Har), 7.41e7.49 (m, 5H, Har), 7.50e7.55 (m, 2H, Har), 7.73e7.77 (m, 2H, Har), 7.79e7.83 (m, 2H, Har) ppm; 13C NMR (150 MHz, CDCl3): d ¼ 22.7 (CH3), 22.9 (CH3), 27.0 (CH(CH3)2, 37.8 (CHN), 39.6 (CHN), 41.5 (CH2CH(CH3)2, 120.4 (d, J ¼ 8.5 Hz, Car), 121.7 (d, J ¼ 12,0 Hz, Car), 124.7 (Car), 125.4 (d, J ¼ 7.7 Hz, Car), 128.2 (d, J ¼ 6.1 Hz, Car), 128.3 (d, J ¼ 12.0 Hz, Car), 131.3 (d, J ¼ 2.1 Hz, Car), 131.4 (d, J ¼ 3.2 Hz, Car), 131.7 (d, J ¼ 9.8 Hz, Car), 132.1 (Car), 132.2 (Car), 132.9 (Car), 133.2 (d, J ¼ 2.1 Hz, Car), 133.6 (Car), 133.7 (Car), 134.4 (Car), 134.7 (d, J ¼ 9.8 Hz, Car), 157.8 (d, J ¼ 4.6 Hz, Car) ppm; 31P NMR (243 MHz, CDCl3): d ¼ 31.37 ppm; Anal. calcd. for C24H26NOP: C 76.80, H 6.93, N 3.73; found: C 76.71, H 6.97, N 3.78. 4.7.4. (2S)-1-[2-(diphenylphosphinoyl)phenyl]-2-phenylaziridine (L9) Yellowish oil (0.53 g, 67%); þ58.12 (c 0.5, CHCl3); 1H NMR (600 MHz, CDCl3): d ¼ 2.01 (d, 1H, J ¼ 3.5 Hz, CHN), 2.58 (d, 1H, J ¼ 6.5 Hz, CHN), 3.34e3.36 (m, 1H, CHN), 6.75e6.87 (4m, 5H, Har), 6.95e6.96 (m, 3H, Har), 7.06e7.28 (3m, 7H, Har), 7.37e7.38 (2m, 4H, Har) ppm; 13C NMR (150 MHz, CDCl3): d ¼ 41.6 (CHN), 42.4 (CHN), 120.5 (3Car), 122.1, 122.2 (2Car), 124.7 (Car), 125.4 (4Car), 126.0 (Car), 126.9 (d, J ¼ 4.3 Hz, Car), 128.2 (d, J ¼ 3.4 Hz, 2Car), 128.4 (d, J ¼ 3.4 Hz, Car), 131.3 (d, J ¼ 2.3 Hz, Car), 131.4 (d, J ¼ 9.7 Hz, 2Car), 131.7 (d, J ¼ 8.7 Hz, Car), 131.9 (d, J ¼ 9.7 Hz, Car), 133.4 (d, J ¼ 9.7 Hz, Car), 134.3 (Car), 135.0 (Car), 156.8 (d, J ¼ 4.3 Hz, Car) ppm; 31P NMR (243 MHz, CDCl3): d ¼ 35.52 ppm; Anal. calcd. for C26H22NOP: C 78.99, H 5.57, N 3.54; found: C 79.03, H 5.61, N 3.58. 4.8. Asymmetric Michael reaction e general protocol [13] An aldehyde (10.0 mmol) was added to a solution of b-nitrostyrene (0.149 g, 1 mmol) and catalyst (0.1 mmol) in dichloromethane (4 mL) at 0  C. The mixture was stirred overnight at this temperature and then concentrated in vacuo. The crude reaction mixture was purified via column chromatography (hexane and ethyl acetate in gradient) to obtain the Michael adducts. The

[1] [2] [3] [4] [5] [6] [7] [8] [9] [10] [11] [12] [13] [14] [15] [16] [17] [18] [19] [20] [21]

[22] [23] [24] [25] [26] [27] [28] [29] [30] [31] [32] [33] [34] [35] [36]

H. Pellissier, Tetrahedron 63 (2007) 9267e9331. A. Dondoni, A. Massi, Angew. Chem. Int. Ed. 47 (2008) 4638e4660. J. Alem
an, S. Cabrera, Chem. Soc. Rev. 42 (2013) 774e793. Y. Zhang, W. Wang, Catal. Sci. Technol. 2 (2012) 42e53. C. Hui, P. Pu, J. Xu, Chem. Eur. J. 23 (2017) 4023e4036.
pe
che, R. Halder, B. List, Angew. Chem. Int. Ed. 47 P. García-García, A. Lade (2008) 4719e4721. T. Ishii, S. Fujioka, Y. Sekiguchi, H. Kotsuki, J. Am. Chem. Soc. 126 (2004) 9558e9559. X. Li, Z.-G. Xi, S. Luo, J.-P. Cheng, Org. Biomol. Chem. 8 (2010) 77e82. J.-F. Bai, L.-L. Wang, L. Peng, Y.-L. Guo, L.-N. Jia, F. Tian, G.-Y. He, X.-Y. Xu, L.X. Wang, J. Org. Chem. 77 (2012) 2947e2953. F. Yu, H. Hu, X. Gu, J. Ye, Org. Lett. 14 (2012) 2038e2041. X. Du, D. Yin, Z. Ge, X. Wang, R. Li, RSC Adv. 7 (2017) 24547e24550.
le, F. Dumas, A. Guingant, Tetrahedron: Asymmetry 3 J. d`Angelo, D. Desmae (1992) 459e505. R.-S. Luo, J. Weng, H.-B. Ai, G. Lu, A.S.C. Chan, Adv. Synth. Catal. 351 (2009) 2449e2459. N. Prabagaran, S. Abraham, G. Sundararajan, Arkivoc vii (2002) 212e226. E. Emori, T. Arai, H. Sasai, M. Shibasaki, J. Am. Chem. Soc. 120 (1998) 4043e4044. € Dog an, E. Çag li, Turk. J. Chem. 39 (2015) 290e296. O. € Dogan, D. Tan, Tetrahedron: Asymmetry 26 (2015) 1348e1353. O. € € ksüz, O. Dogan, P.P. Garner, Tetrahedron: Asymmetry 21 (2010) S. Ero 2535e2541. € O. Dogan, M. Isci, M. Aygun, Tetrahedron: Asymmetry 24 (2013) 562e567. € Dogan, A. Bulut, M. Ali Tecimer, Tetrahedron: Asymmetry 26 (2015) O. 966e969.
ski, M. Rachwalski, M. Kwiatkowska, M. Mikołajczyk, P. Kiełbasin
, F.P.J.T. Rutjes, Tetrahedron: Asymmetry W.M. Wieczorek, M. Szyrej, L. Sieron 18 (2007) 2108e2112.
ski, Tetrahedron: Asymmetry 22 (2011) M. Rachwalski, S. Le
sniak, P. Kiełbasin 1087e1089.
ski, S. Le
sniak, M. Rachwalski, T. Leenders, S. Kaczmarczyk, P. Kiełbasin F.P.J.T. Rutjes, Org. Biomol. Chem. 11 (2013) 4207e4213. S. Le
sniak, M. Rachwalski, A.M. Pieczonka, Curr. Org. Chem. 18 (2014) 3045e3065.
ski, ChemCatChem 7 M. Rachwalski, Z. Wujkowska, S. Le
sniak, P. Kiełbasin (2015) 3589e3592. K. Tani, M. Yabuta, S. Nakamura, T. Yamagata, J. Chem. Soc. Dalton Trans. (1993) 2781e2789. B. Breit, G. Heckmann, S.K. Zahn, Chem. Eur. J. 9 (2003) 425e434. D. Tanner, P. Wyatt, F. Johansson, S.K. Bertilsson, P.G. Andersson, Acta Chem. Scand. 53 (1999) 263e268. S. Dorok, C. Rothe, O. Fadhel, F.Cardinali, EP2786434, 2015, B1. S. Kotani, Y. Shimoda, M. Sugiura, M. Nakajima, Tetrahedron Lett. 50 (2009) 4602e4605. M. Sugiura, N. Sato, S. Kotani, M. Nakajima, Chem. Commun. (2008) 4309e4311. S.E. Denmark, G.L. Beutner, Angew. Chem. Int. Ed. 47 (2008) 1560e1638. S. Rossi, M. Benaglia, R. Cirilli, T. Benincori, Asymmetric Catal. (2015) 17e25. B. Tan, X. Zeng, Y. Lu, P.I. Chua, G. Zhong, Org. Lett. 11 (2009) 1927e1930. M. Stankevi c, J. Pisklak, K. Włodarczyk, Tetrahedron 72 (2016) 810e824. Y. Tanaka, T. Mino, K. Akita, M. Sakamoto, T. Fujita, J. Org. Chem. 69 (2004) 6679e6687.