Enantioselective additions of diethylzinc to aldehydes catalyzed by titanate(IV) complex with chiral bidentate bis-amide ligands based on cyclopropane backbone

Abdullah M.A. Al Majid; Mohammad Shahidul Islam; Zeid Abdullah Al-Othman; Ahlam F. Al-Salhoob

doi:10.1016/j.arabjc.2012.12.036

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Original article

10 (

1_suppl

); S964-S970

doi:

10.1016/j.arabjc.2012.12.036

Enantioselective additions of diethylzinc to aldehydes catalyzed by titanate(IV) complex with chiral bidentate bis-amide ligands based on cyclopropane backbone

Abdullah M.A. Al Majid, Mohammad Shahidul Islam^⁎, Zeid Abdullah Al-Othman, Ahlam F. Al-Salhoob

Department of Chemistry, Faculty of Science, King Saud University, P.O. Box 2455, Riyadh 11451, Saudi Arabia

⁎Corresponding author. Tel.: +966 14675884; fax: +966 1 4675992. mislam@ksu.edu.sa (Mohammad Shahidul Islam), shahid.10amui@gmail.com (Mohammad Shahidul Islam),

Published: 2013-02-01

Disclaimer:
This article was originally published by Elsevier and was migrated to Scientific Scholar after the change of Publisher.

Peer review under responsibility of King Saud University.

Abstract

A set of chiral bis-amide ligands (4a–d and 5a–d) were obtained easily from readily available starting materials in a straightforward manner via acid chloride reaction of the parent Feist’s acid. These ligands have been tested as chiral catalysts for the enantioselective addition of diethylzinc to aromatic aldehydes in the presence of Ti(OⁱPr)₄ as a co-additive. Very good enantioselectivity was obtained for 4-bromobenzaldehyde while in the case of 2,4-dichlorobenzaldehyde very low enantioselectivity was observed. The influence of solvent, temperature and the alkyl group substituents has been studied, and in the best case, an enantiomeric excess upto 95% has been achieved by using only 10 mol % of the chiral bis-amides ligand 5b.

Keywords

C2 symmetric bis-amide ligand

Diethylzinc addition

Enantioselective catalysis

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1 Introduction

The enantioselective addition of organometallic reagents (Geng and Zhan, 2010) to prochiral carbonyl compounds in the presence of chiral catalysts, has drawn a great deal of attention to the synthetic organic chemists, because of its simple reaction conditions, low toxicity of the zinc metal, and the huge number of functional group tolerance. Addition of organozinc is one of the most reliable reactions for testing the effectiveness of newly developed chiral ligands (Pu and Yu, 2001; Reetz, 1999; Noyori, 1994 ). It is also a very useful reaction for the preparation of chiral secondary alcohols and tert-alcohols, which are the key building blocks in the fine chemical and pharmaceutical industries (Soai and Shibata, 1999). Furthermore, chiral alcohols are pervasive in the skeleton of drug molecules, natural products, and also important organic precursors for the preparation of many other functional organic entities (Ailing et al., 2006). Therefore an asymmetric C–C bond construction, generation of stereogenic center in molecules have led to its application in the preparation of optically active alcohols for the further synthesis of natural products, drug molecules and biologically active molecules (Zhi-Long et al., 2009; Belén et al., 2010). One of the most effective, convenient and useful methods for the asymmetric synthesis of sec- and tert-alcohols is the enantioselective addition of dialkylzinc to carbonyl compounds in the presence of a wide variety of chiral auxiliaries (Noyori and Kitamura, 1991; Soai and Niwa, 1992). A large number of chiral ligands have been reported in the literature and successfully have been employed in several asymmetric additions of diethylzinc to aldehydes, such as β-amino alcohols (Andres et al., 2010; Le-snik et al., 2009; Rodríguez-Escrich et al., 2008; Tanaka et al., 2006 ), amino thiols and disulfides (Braga et al., 2005, 2008; Mellah et al., 2007 ), aminonaphthols (Ko et al., 2002; Liu et al., 2001), imines (Mino et al., 2006; Qin et al., 2005), diamines and their derivatives (Gao et al., 2010; Burguete et al., 2008; Mastranzo et al., 2006; Brunel, 2005 ), diols (Roudeau et al., 2006; Sarvary et al., 2002), Binols (Shaohua and Zaher, 2009; Yan et al., 2008), diselenides, bisoxazolidines (Jacek et al., 2009; Devarajulu et al., 2007; Shen et al., 2000 ), disulfonamides (Hirose et al., 2011; Huang et al., 2007), and diamide (Bateman et al., 2008; Blay et al., 2007). Moreover, asymmetric addition of diethylzinc to aldehyde is the most successful and still vigorously pursued area in asymmetric C–C bond formation (Manabu et al., 2006; Noyori and Kitamura, 1991). Thus, the addition of diethylzinc to aldehyde has become a classical test in the design of new ligands for catalytic asymmetric synthesis. Thenceforth, with the development of diverse ligand structures and reaction conditions for the enantioselective catalytic reactions, chiral bis-amides would be an attractive choice of catalysts, as a result of their easy availability and simple reaction conditions.

Despite the enormous success of axial chiral ligands in asymmetric synthesis, a limited number of chiral diamide type ligands have been reported (Umesh et al., 2012; Nallamuthu et al.,2009). To the best of our knowledge, there are no reported ligands based on Feist’s acid in the long catalyst list of the asymmetric addition of diethylzinc to aldehydes. Therefore, it would be of great interest to explore the catalytic activity of C₂ symmetric bis-amide ligands with a scaffold of trans-3-methylenecyclopropane-1,2-dicarboxylic acid. Herein, we report the application of C₂ symmetric bis-amide ligands obtained from Feist’s acid, for the catalytic enantioselective addition of diethylzinc with 4-bromobenzaldehyde and 2,4-dichlorobenzaldehyde.

2 Experimental

2.1

2.1 General

All the moisture and air sensitive reactions were carried out under an inert atmosphere using an argon filled glove box and standard Schlenk-line techniques. All the reactions were monitored by thin layer chromatography (TLC). Flash chromatography purifications were performed using silica gel (100–200 mesh). Diethylzinc and Ti(OⁱPr)₄ were purchased from Aldrich. Triethylamine and diisopropylamine were dried over sodium hydroxide. Diethyl ether and tetrahydrofuran were distilled from sodium benzophenone ketyl. Chloroform, dichloromethane, benzene, toluene and dimethylformamide were dried using calcium hydride. Petroleum ether (PE), hexane and ethyl acetate were distilled for column chromatography prior to use. ¹H and ¹³C-NMR spectra were recorded on a Jeol-400 spectrometer (¹H 400 MHz, ¹³C 100 MHz): using CDCl₃ as solvent. The chemical shifts (δ in ppm) were referenced internally using residual non deuterated solvent resonance shift and reported to trimethylsilane (TMS). Coupling constants (J) are taken in Hertz (Hz). Optical rotation was recorded on a high sensitive automatic ‘A. KRÜSS OPTRONOCS' polarimeter. Elemental analyses were performed on a Perkin Elmer 2400 Elemental Analyzer. Enantiomeric excess (ee) determination was carried out using HPLC with a chiral Nucleosil^® column; Solvent, 90:10 acetonitrile/water; Flow rate 0.5 mL min⁻¹; 220 nm UV detection. IR spectra were recorded on a Model FTIR-800 Infrared FT-IR Spectrometer using neat for liquids. Mass spectrometric analysis was conducted by using ESI mode on AGILENT Technologies 6410-triple quad LC/MS instrument.

2.2

2.2 General procedure for enantioselective addition of diethylzinc to aromaticaldehydes

Ligand (10 mol%, 0.1 equiv.) and Ti(OⁱPr)₄ (922 mg, 3.24 mmol, 1.2 equiv.) were dissolved in dry toluene (5 ml) under argon atmosphere. The resulting mixture was heated at 60 °C for 20 min. Then it was cooled to 0–4 °C and a solution of diethylzinc (5.4 ml, 5.4 mmol, 2 equiv., 1M in hexane) was added drop wise to the reaction mixture. The resulting solution was stirred for 30 min at the identical condition. Aromaticaldehyde (2.7 mmol, 1 equiv.) dissolved in dry toluene (5 ml) was added slowly at this temperature. The reaction was stirred for the appointed time mentioned in Tables 1 and 2 for different conditions. The reaction mixture was then quenched with 1M hydrochloric acid and extracted with ethyl acetate (3 × 10 ml). The combined organics were extracts and dried over anhydrous Mg₂SO₄. The solvents were removed under reduced pressure to afford crude product. The crude alcohol was purified by flash column chromatography on silica gel (100–200 mesh) to afford the pure product. The enantiomeric excess was determined by chiral HPLC ‘Nucleosil® chiral-1' column.

2.3

2.3 Spectral data for 1-(4-bromophenyl) -1-propanol

IR (cm^–1): 3359 (bs, OH str.), 2965 (s), 1486 (s), 1071 (s), 1009 (s), 820 (s), 542 (m); ¹H-NMR (CDCl₃, 400 MHz) δ 0.88 (t, 3H, J = 7.32 Hz, CH₃), 1.69 – 1.74 (m, 2H, CH₂), 2.03 (s, 1H, OH), 4.54 (t, 1H, J = 6.60 Hz, CH), 7.18 – 7.20 (d, 2H, J = 8.04 Hz, ArH), 7.44 – 7.46 (d, 2H, J = 8.08 Hz, ArH); ¹³C-NMR (CDCl_3, 100 MHz): δ 10.05 (CH₃), 31.98 (CH₂), 76.80 (CH), 121.25 (ArCBr), 127 (ArC), 131.52 (ArC); Anal. Calcd. for C₉H₁₁BrO: C, 50.26; H, 5.15; Br, 37.17; Found: C, 50.38; H, 5.49; LC/MS (ESI): m/z = 215.12 {[M]⁺_, for ⁷⁹Br} and 217.1{ [M + 2]⁺, for ⁸¹Br}.

${[α]}_{D}^{25}$ = + 23.25 (c = 0.31, CHCl₃); % e.e. 60.69 (R) ; t_R = 5.047 min for (S) and t_R = 5.326 min for (R).
${[α]}_{D}^{25}$ = + 19.21 (c = 0.27, CHCl₃); % e.e. 71.53 (R) ; t_R = 5.073 min for (S) and t_R = 5.376 min for (R).
${[α]}_{D}^{25}$ = + 23.25 (c = 0.31, CHCl₃); % e.e. 71.70 (R) ; t_R = 5.023 min for (S) and t_R = 5.341 min for (R).
${[α]}_{D}^{25}$ = + 29.57 (c = 0.30, CHCl₃); % e.e. 80.72 (R) ; t_R = 5.034 min for (S) and t_R = 5.378 min for (R).
${[α]}_{D}^{25}$ = + 33.26 (c = 0.28, CHCl₃); % e.e. 84.69 (R) ; t_R = 5.019 min for (S) and t_R = 5.372 min for (R).
${[α]}_{D}^{25}$ = + 37.36 (c = 0.39, CHCl₃); % e.e. 60.69 (R) ; t_R = 5.040 min for (S) and t_R = 5.369 min for (R).
${[α]}_{D}^{25}$ = + 22.79 (c = 0.29, CHCl₃); % e.e. 58.63 (R) ; t_R = 5.078 min for (S) and t_R = 5.336 min for (R).
${[α]}_{D}^{25}$ = + 26.83 (c = 0.40, CHCl₃); % e.e. 81.00 (R) ; t_R = 5.036 min for (S) and t_R = 5.378 min for (R).

2.4

2.4 Spectral data for 1-(2,4-dichlorophenyl)-1-propanol

IR (cm^–1): 3351 (bs, OH str.), 2968 (s), 1467 (s), 1381 (s), 1097 (s), 1047 (s), 977 (s), 840 (s), 818 (s), 566 (s); ¹H-NMR (CDCl₃, 400 MHz) δ 0.95 (t, 3H, J = 7.32 Hz, CH₃), 1.67 – 1.71 (m, 2H, CH₂), 2.20 (s, 1H, OH), 4.98 (t, 1H, J = 2.20 Hz, CH), 7.31 – 7.32 (d, 2H, J = 2.2 Hz, ArH), 7.44 – 7.46 (d, 2H, J = 8.04 Hz, ArH); ¹³C-NMR (CDCl_3, 100 MHz): δ 9.98 (CH₃), 30.54 (CH₂), 71.53 (CH), 127.39 (ArC), 128.22 (ArC), 129.10 (ArC), 132.54 (ArC), 133.37 (ArC), 140.69 (ArC); Anal. Calcd. for C₉H₁₀Cl₂O: C, 52.71; H, 4.91; Cl, 34.57; O, 7.80; Found: C, 52.56; H, 5.18; LC/MS (ESI): m/z = 205.02 {[M]⁺, for ³⁵Cl} and 207.2 {[M + 2]⁺, for ³⁷Cl}.

${[α]}_{D}^{25}$ = + 6.72 (c = 0.30, CHCl₃); % e.e. 12.00 (R) ; t_R = 5.191 min for (S) and t_R = 7.441 min for (R).
${[α]}_{D}^{25}$ = + 3.80 (c = 0.28, CHCl₃); % e.e. 16.44 (R) ; t_R = 5.217 min for (S) and t_R = 7.472 min for (R).
${[α]}_{D}^{25}$ = + 8.52 (c = 0.24, CHCl₃); % e.e. 25.50 (R) ; t_R = 5.206 min for (S) and t_R = 7.434 min for (R).
${[α]}_{D}^{25}$ = + 7.94 (c = 0.31, CHCl₃); % e.e. 9.13 (R) ; t_R = 5.199 min for (S) and t_R = 7.403 min for (R).
${[α]}_{D}^{25}$ = − 5.59 (c = 0.25, CHCl₃); % e.e. 16.56 (S) ; t_R = 5.208 min for (R) and t_R = 7.416 min for (S).
${[α]}_{D}^{25}$ = − 4.79 (c = 0.41, CHCl₃); % e.e. 17.00 (S) ; t_R = 5.200 min for (R) and t_R = 7.421 min for (S).
${[α]}_{D}^{25}$ = − 2.46 (c = 0.32, CHCl₃); % e.e. 11.70 (S) ; t_R = 5.214 min for (R) and t_R = 7.408 min for (S).
${[α]}_{D}^{25}$ = − 6.08 (c = 0.25, CHCl₃); % e.e. 10.30 (S) ; t_R = 5.205 min for (R) and t_R = 7.424 min for (S).

3 Result and discussion

The reaction conditions and synthetic strategies, adopted in this work, have been described in Schemes 1 and 2.

Outline for the synthesis of ligands (4a–d and 5a–d).

Addition of diethylzinc to aldehydes using ligands 4a–d and 5a–d (10 mol%).

Scheme 1 shows the brief outline of synthetic routes leading to the formation of bis-amide ligands (4a–d) and (5a–d) based on chiral cyclopropane backbone, which is to be used as base catalysts. Synthesis of these chiral ligands initially requires the preparation and the resolution of chiral scaffold trans-3-methylene-1,2-dicarboxylic acid (Feist’s acid) reported by Almajid and coworkers (Al-Majid et al., 2012a,b).¹⁹ The catalytic activity of these ligands was investigated for the addition of diethylzinc to aldehydes (Scheme 2).

Since aromatic aldehydes are one of the most studied substrates in the enantioselective addition of diethylzinc to aldehydes, we have employed these ligands as a base catalyst to find the optimum reaction parameters such as the effect of solvents, the relative amount of catalyst loading and the temperature, for the enantioselective addition of diethylzinc to 4-bromobenzal-dehyde. The results of our initial investigation with (1R,2R)-4a and (1S,2S)-5a are shown in Table 1.

Using different reaction parameters, moderate to good chemical and low to high enantiomeric excesses were obtained. The optimum condition for both the chemical yields and enantiomeric excesses was achieved with the combination of the substrate, Et₂Zn, Ti(OⁱPr)₄ and the ligand (1:2:0.1.2:0.1) molar ratio in toluene at RT. for 24 h (Table 1; entry 8 and 9). The reaction carried out in different solvents such as benzene, Et₂O, CH₂Cl₂ and THF, afforded low yield with poor enantiomeric excess (Table 1; entries 3, 5, 7 and 4 accordingly). As compared to other solvents, toluene gave better yield and enantiomeric excess in all cases (Table 1; entries 1, 2, 6, 8 and 9). For achieving better enantioselectivity, some reactions were carried out in a mixture (1:1 ratio) of two solvents and for a longer time period (Table 1; entries 12–15), but neither enantioselectivity nor chemical yields were improved. Increasing the loading percentage of ligand from 5 to 10 mol% led to the improvement of yield from 48 to 63% and 51% to 61% ee (Table 1; entries 6 & 8). The yield of the reactions also could be improved on increasing the molar ratio of diethylzinc (Table 1; entries 2, 6, 8). Significantly, the effect of temperature was also observed, at lower temperature (0–10 °C for 3 h and then for 21 h at r.t.) high enantioselectivity upto 78% and poor chemical yields were observed as expected. While at higher temperature the reaction took only 6 h to complete and produced high chemical yield with poor enantiomeric excess (Table 1; entries 10^a and 11^b). Optimum conditions were achieved, using 10 mol% of the ligand, 2 eq. of diethylzinc, and 1.2 eq. of Ti(OⁱPr)₄ in toluene (Table 1; entry 8 & 9). Under the optimum parameters, all the chiral bis-amide ligands 4a–d & 5a–d were employed for the asymmetric addition of diethylzinc to 4-bromobenzaldehyde and 2,4-dichlorobenzaldehyde and the corresponding results are shown in Table 2.

On addition of diethylzinc to 4-bromobenzaldehyde under opyimized condition, all ligands produced (R)-1-(4-bromophenyl)-1-propanol with good chemical yield (43–70%) as well as enantioselectivity (59–95%) (Table 2, entries 1a–8a). However, ligand 5b gave highest chemical yield (70%) and 95% e.e. under the standard set of reaction conditions (Table 2, entry 6^a). But using the same parameters, 2,4-dichlorobenzaldehyde afforded 1-(2,4-dichlorophenyl)-1-propanol with very poor e.e (9–26%) and moderate chemical yield (52–65%). The possible reason for low chemical yield and poor enantioselectivity is due to chlorine atom at the ortho position of 2,4-dichloro benzalaldehyde. The proposed mechanism for the enantioselective addition of diethylzinc to aldehyde in the presence of Ti(OⁱPr)₄ has been shown in Fig. 1.

Proposed mechanism for the enantioselective addition of diethylzinc to aldehyde in the presence of Ti(OiPr)4.

The probable pathway has also been shown in Fig. 2, for the formation of both enantiomers. Fig. 3 shows both the difficult and easy way of co-ordination for the oxygen atom toward the metal center with proper orientation in the case of both aldehydes.

Probable mechanism for the formation of opposite enantiomer.

4 Conclusions

This asymmetric alkylation approach provides a useful route for the synthesis of some chiral secondary alcohols. We have conveniently applied the novel bis-amide ligands (4a–d & 5a–d) to the catalytic asymmetric addition of diethylzinc to aldehydes under several conditions. The bis-amide ligands provide excellent yield and good enantioselectivity. However, these ligands are less effective in the case of 2,4-dichlorobenzaldehyde. The oxygen atoms of aldehyde with ortho substituents, thought to direct to the metal center of the complex, were difficult and led to a decrease in both the yield and enantioselectivity. Further work is in progress in our laboratory with the aim of expanding the use of these inexpensive chiral compounds to other enantioselective processes.

Acknowledgment

The authors extend their appreciation to the Deanship of Scientific Research, at King Saud University for funding the work through the research group project No. RGP-VPP-044.

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Appendix A

Supplementary data

Supplementary data associated with this article can be found, in the online version, at http://dx.doi.org/10.1016/j.arabjc.2012.12.036.

Appendix A

Supplementary data

Supplementary data 1

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Introduction

Experimental

General
General procedure for enantioselective addition of diethylzinc to aromaticaldehydes
Spectral data for 1-(4-bromophenyl) -1-propanol
Spectral data for 1-(2,4-dichlorophenyl)-1-propanol

Result and discussion

Conclusions

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[1] Ailing H., Jintang Z.J.F., Zhiyong W., . Tetrahedron: Asymmetry. 2006;17:2101.

[2] Al-Majid A.M.A., Al-Othman Z.A., Islam M.S., . Helv. Chim. Acta.. 2012;95:268.

[3] Al-Majid A.M.A., Islam M.S., Al-Othman Z.A., Al-Salhoob A.F., Barakat A., . Molecules. 2012;17:5550.

[4] Andres C., Infante R., Nieto J., . Tetrahedron: Asymmetry. 2010;21:2230.

[5] Bateman L., Breeden S.W., O'Leary P., . Tetrahedron: Asymmetry. 2008;19:391.

[6] Belén A.M., Isabel B., Noèlia C., Jorge E., Santiago V.L., . Tetrahedron: Asymmetry. 2010;21:982.

[7] Blay G., Fernández I., Olmos V.H., Marco-Aleixandre A., Pedro J.R., . J. Mol. Catal. A: Chem.. 2007;276:235.

[8] Braga A.L., Alves E.F., Silveira C.C., Zeni G., Appelt H.R., Wessjohann L.A., . Synthesis. 2005;4:588.

[9] Braga A.L., Galetto F.Z., Rodrigues O.E.D., Silveira C.C., Paixao M.W., . Chirality. 2008;20:839.

[10] Brunel J.M., . Chem. Rev.. 2005;105:857.

[11] Burguete M.S., Escorihuela J., Luis S.V., Lledos A., Ujaque G., . Tetrahedron. 2008;64:9717.

[12] Devarajulu S., Thanikachalam G., Vadivelu S.C., . Tetrahedron Lett.. 2007;48:623.

[13] Gao Q., Yao Q.J., Zaher M.A.J., . Tetrahedron. 2010;66:4195.

[14] Geng Xu., Zhan Z.L., . Chin. Chem. Lett.. 2010;21:309.

[15] Gonzalo B., Isabel F., Alcia M.-A., Jose R.P., . Tetrahedron: Asymmetry. 2005;16:1207.

[16] Hirose T., Sugawara K., Kodama K., . J. Org. Chem.. 2011;76:5413.

[17] Huang Z., Lai H., Qin Y., . J. Org. Chem.. 2007;72:1373.

[18] Jacek S., Zbigniew R., Aleksandra S., Andrzej W., . Tetrahedron. 2009;65:10162.

[19] Javier G.-S., Vicente G., Francisca R., . Tetrahedron: Asymmetry. 2006;17:449.

[20] Ko D.H., Kim K.H., Ha D.C., . Org. Lett.. 2002;4:3759.

[21] Le-snik S., Rachwalski M., Sznajder E., Kiezbasi-nski P., . Tetrahedron: Asymmetry. 2009;20:2311.

[22] Liu D.-X., Zhang L.-C., Wang Q., Da C.-S., Xin Z.-Q., Wang R., Choi M.C.K., Chan A.S.C., . Org. Lett.. 2001;3:2733.

[23] Manabu H., Takashi M., Kazuaki I., . J. Org. Chem.. 2006;71:6474.

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Entry	Ligand	Ti(OⁱPr)₄/ ligand	Et₂Zn	Solvent	Time	Yield (%)^c	e.e. (%)^d
1	(1R,2R)-4a	1.0/0.05	1.2 eq	Toluene	10 h	32	44
2	(1S,2S)-5a	1.0/0.05	1.2 eq	Toluene	24 h	29	47
3	(1R,2R)-4a	1.0/0.05	1.2 eq	Benzene	30 h	15	13
4	(1S,2S)-5a	1.0/0.05	1.2 eq	THF	24 h	23	19
5	(1R,2R)-4a	1.0/0.05	1.2 eq	Ether	36 h	19	17
6	(1R,2R)-4a	1.2/0.05	1.5 eq	Toluene	24 h	48	51
7	(1S,2S)-5a	1.2/0.05	1.5 eq	CH₂Cl₂	24 h	13	67
8	(1R,2R)-4a	1.2/0.1	2.0 eq	Toluene	24 h	63	61
9	(1S,2S)-5a	1.2/0.1	2.0 eq	Toluene	24 h	70	85
10^a	(1R,2R)-4a	1.2/0.1	2.0 eq	Toluene	30 h	30	78
11^b	(1R,2R)-4a	1.2/0.1	2.0 eq	Toluene	6 h	83	15
12	(1R,2R)-4a	1.2/0.1	2.0 eq	Benzene/Hexane	30 h	7	10
13	(1R,2R)-4a	1.2/0.1	2.0 eq	Toluene/Hexane	30 h	10	35
14	(1R,2R)-4a	1.2/0.1	2.0 eq	Toluene/ CH₂Cl₂	24 h	24	43
15	(1R,2R)-4a	1.2/0.1	2.0 eq	Toluene/THF	24 h	31	41

Entry	Ligand	%Mol	Time	Yield ^c (%)	${[α]}_{D}^{25}$ ; (in CHCl₃)^d	e.e.^e (%)	Config.^f
1^a	(1R,2R)-4a	10	24 h	63	+23.25; (c, 0.31)	61	(R)
2^a	(1R,2R)-4b	10	24 h	71	+27.30; (c, 0.34)	72	(R)
3^a	(1R,2R)-4c	10	24 h	76	+19.21; (c, 0.27)	72	(R)
4^a	(1R,2R)-4d	10	24 h	43	+29.57; (c, 0.30)	81	(R)
5^a	(1S,2S)-5a	10	24 h	70	+33.26; (c, 0.28)	85	(R)
6^a	(1S,2S)-5b	10	24 h	70	+37.36; (c, 0.39)	95	(R)
7^a	(1S,2S)-5c	10	24 h	58	+22.79; (c, 0.29)	59	(R)
8^a	(1S,2S)-5d	10	24 h	51	+26.83; (c, 0.40)	81	(R)
9^b	(1R,2R)-4a	10	24 h	65	+6.78; (c, 0.30)	12	(R)
10^b	(1R,2R)-4b	10	24 h	68	+3.80; (c, 0.28)	16	(R)
11^b	(1R,2R)-4c	10	24 h	64	+8.52; (c, 0.24)	26	(R)
12^b	(1R,2R)-4d	10	30 h	56	+7.94; (c, 0.31)	9	(R)
13^b	(1S,2S)-5a	10	24 h	60	−5.59; (c, 0.25)	16	(S)
14^b	(1S,2S)-5b	10	24 h	64	−4.79; (c, 0.41)	17	(S)
15^b	(1S,2S)-5c	10	24 h	52	−2.46; (c, 0.32)	11	(S)
16^b	(1S,2S)-5d	10	30 h	49	−6.08; (c, 0.25)	10	(S)

Enantioselective additions of diethylzinc to aldehydes catalyzed by titanate(IV) complex with chiral bidentate bis-amide ligands based on cyclopropane backbone

Abstract

Keywords

C2 symmetric bis-amide ligand

Diethylzinc addition

Enantioselective catalysis

1 Introduction

2 Experimental

2.1 General

2.2 General procedure for enantioselective addition of diethylzinc to aromaticaldehydes

2.3 Spectral data for 1-(4-bromophenyl) -1-propanol

2.4 Spectral data for 1-(2,4-dichlorophenyl)-1-propanol

3 Result and discussion

4 Conclusions

Acknowledgment

References

Appendix A

Supplementary data

Appendix A

Supplementary data

Supplementary data 1

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