α-Hydroxy carboxylic acids as ligands for enantioselective diethylzinc additions to aromatic and aliphatic aldehydes

Tetrahedron 60 (2004) 9163–9170

a-Hydroxy carboxylic acids as ligands for enantioselective diethylzinc additions to aromatic and aliphatic aldehydes Tomasz Bauer* and Joanna Gajewiak Department of Chemistry, Warsaw of University, u1. Pasteura 1, PL-02-093 Warsaw, Poland Received 27 May 2004; revised 1 July 2004; accepted 23 July 2004 Available online 25 August 2004

Abstract—The first examples of the enantioselective titanium-mediated diethylzinc additions to aromatic and aliphatic aldehydes catalyzed by optically active a-hydroxy acids are presented. The reactions proceed with very good yield and good asymmetric induction. Enantioselectivities up to 90% are obtained depending on ligand and aldehyde used. A stereochemical model for the reaction is proposed. q 2004 Elsevier Ltd. All rights reserved.

1. Introduction The enantioselective organometallic addition to aldehydes is a valuable method for the synthesis of optically active secondary alcohols and several efficient catalysts have been developed, various types of chiral ligands can be used for such additions. Since 1986, when DAIB was introduced by Noyori,1 the amount of very useful and efficient dialkylamino alcohols has grown dramatically,2 and now includes not only dialkylamino alcohols but also amino thiols,3 oxazolines4–6 and even diols such as TADDOLs7,8 and BINOLs.9–11 Further progress in enantioselective additions to aldehydes was achieved, when Ohno and co-workers reported diethylzinc additions in the presence of titanium tetraisopropoxide and a chiral bissulfonamide.12 Since then, extensive synthetic studies were conducted and a-hydroxy sulfonamides and bissulfonamides were proven to be very efficient ligands for additions of dialkylzincs.13–17 Although the exact mechanism of the process is not known, recent structural and mechanistic investigations showed that the active catalytic intermediates could be an ethyltitanium species derived from the transfer of an ethyl group from zinc to titanium or a bimetallic species containing an ethylzinc compound.15 Both ligand accelerated diethylzinc additions and alkyltitanium additions to carbonyl compounds exhibit excellent chemoselectivity.18 For mixtures of aldehydes and ketones, only addition to the aldehyde carbonyl group is observed whilst ketones remain intact. This led us to the conclusion that carboxylic acids could serve as ligands in Ti(OiPr)4 catalyzed additions of diethylzinc to aldehydes. Keywords: Diethylzinc; Titanium tetraisopropoxide; a-Hydroxy acids; Aldehydes; Enantioselective. * Corresponding author. Tel.: C48-22-822-02-11x273; fax: C48-22-82259-96; e-mail: [email protected] 0040–4020/$ - see front matter q 2004 Elsevier Ltd. All rights reserved. doi:10.1016/j.tet.2004.07.060

For the second coordination site, we chose the hydroxy group so that our ligands belong to the readily accessible family of a-hydroxy acids 1. Recently we have presented a preliminary communication19 on the addition of diethylzinc to benzaldehyde (2) catalyzed by a-hydroxy acids 1 and the purpose of this paper is to give a full account on the enantioselective diethylzinc addition to aromatic and aliphatic aldehydes (Scheme 1). 2. Results and discussion 2.1. Synthesis of a-hydroxy acids 2.1.1. Synthesis by diazotisation of a-amino acids. One of the most straightforward, reliable and inexpensive methods for the synthesis of a-hydroxy acids is diazotisation of a-amino acids. The reaction proceeds with retention of configuration,20,21 and traces of the minor enantiomer, if present, can be removed by recrystallization.22 We have chosen six amino acids 4b–g, which were treated at 0 8C with excess of aqueous sodium nitrate(IV) in the presence of 0.5 M sulfuric acid. The reaction mixture was stirred

Scheme 1. Diethylzinc addition to benzaldehyde in the presence of ahydroxy acids as chiral ligands.

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Scheme 2. Synthesis of a-hydroxy acids by diazotisation.

overnight at room temperature, and after work-up, the resulting a-hydroxy acids 1b–g were crystallized from organic solvents (Scheme 2). For all thus prepared compounds, specific rotations were in good agreement with literature values, except the case of (S)-2-hydroxy-3,3dimethylbutanoic acid (1g). For the sample prepared by us we measured [a]22 D ZC4.1 (cZ1.83, H2O); commercially available (Aldrich) compound had [a]22 D ZC3.3 (c 2.25, 23 or H2O), while the literature value is [a]25 D ZC4.5 (cZ1 24 cZ4 , H2O). At this moment we are not able to say, whether the reason for this discrepancy is presence of the minor enantiomer or chemical impurities. The enantiomeric purity of (S)-2-hydroxy-3,3-dimethylbutanoic acid (1g), as well as rest of the a-hydroxy acids used, will be confirmed by other methods and the results will be reported in due course. This has to be taken into account during analysis of the results of diethylzinc addition. 2.1.2. Synthesis by diastereoselective Friedel–Crafts alkylation. In addition to a-hydroxy acids synthesized from a-amino acids we have also prepared two compounds bearing substituted phenyl rings. Lewis acid catalyzed addition of N-glyoxyloyl-(2R)-bornane-10,2-sultam (5) to methoxy- and isopropoxy tert-butyl benzene (6a and 6b, respectively) proceeded with good yield and diastereoselectivity. Hydrolysis of the chiral auxiliary under mild conditions gave hydroxy acids 1h and 1i (Scheme 3). The details of the synthesis are presented elsewhere.25

enantiomeric excess (77% ee in favor of the product with 1S configuration) was determined by HPLC using a Chiracel OD column. After this first successful experiment we started a systematic investigation of the factors influencing yield and asymmetric induction in this reaction. First, we noted that the reaction performed in the absence of Ti(OiPr)4 is very sluggish and proceeds with low asymmetric induction (Table 1, entry 1). On the other hand, increased bulkiness of the titanium reagent does not influence the reaction and in the presence of Ti(OtBu)4 we obtained similar yield and ee (Table 1, entry 3). Addition of zinc and titanium reagents in the reversed order did not influence enantioselectivity (Table 1, entry 2). To examine effect of the solvent the reaction was carried out in five typical solvents. Methylene chloride was the best one both for chemical yield and asymmetric induction (Table 1, entries 4–8). Once the best solvent was found, we studied the influence of the amount of the ligand and its concentration. The asymmetric induction was only slightly influenced by increased amount of ligand, while the chemical yield dropped from 95 to 80% (Table 2). For further experiments, a concentration of 0.044 mmol/mL and 0.2 equiv of ligand was chosen. The next parameter studied was reaction temperature. Table 3 shows the influence of the temperature and the optimum regarding both yield and enantiomeric excess was observed for room temperature (22 8C).

2.2. Enantioselective diethylzinc addition 2.2.1. Enantioselective diethylzinc addition to aldehydes in the presence of (S)-mandelic acid. In order to confirm considerations presented above, we decided to use commercially available (S)-mandelic acid 1a as a ligand and benzaldehyde 2 as a model carbonyl compound. The reaction was conducted at room temperature in methylene chloride in the presence of 0.2 equiv of mandelic acid, 3 equiv of diethylzinc and 1.4 equiv of titanium tetraisopropoxide. The reaction was stirred overnight, and after TLC showed complete conversion, quenched with aqueous hydrochloric acid. After work-up and chromatography 1-phenyl-1-propanol 3 was isolated in 88% yield. The

The so-called ‘aging’ of the catalyst can seriously influence the results of the reaction. In order to find out, whether our system is prone to such phenomena we performed two series of experiments in which we measured the enantiomeric excess against time of the complexation with titanium and zinc compounds. In the first series, showed that the optimum complexation time for titanium tetraisopropoxide lies between 1 and 1.5 h. Therefore, in the next experiments, the ligand was stirred with Ti(OiPr)4 for 1.5 h. For diethylzinc this optimum was found after 45 min of complexation. The results are presented in Tables 4 and 5. The last two parameters, the influence of which had to be

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Scheme 3. Synthesis of a-hydroxy acids by diastereoselective Friedel–Crafts reaction.

Table 1. Diethylzinc addition in various solvents Entry

Ligand

Solvent

Temperature (8C)

Time (h)

Yield (%)

ee (config.) (%)

1a 1a 1a 1a 1a 1a 1a 1a

CH2Cl2 CH2Cl2 CH2Cl2 CH2Cl2 Toluene n-Hexane THF Et2O

22 22 22 22 22 22 22 22

66 23 23 20 23 24 19 19

73 90 79 88 77 88 40 75

40 (S) 76 (S) 77 (S) 77 (S) 67 (S) 63 (S) 32 (S) 65 (S)

a

1 2b 3c 4 5 6 7 8 a b c

Reaction in the absence of Ti(OiPr)4. Addition order was reversed from Ti(OiPr)4/Et2Zn to Et2Zn/Ti(OiPr)4. Reaction in the presence of Ti(OtBu)4 instead of Ti(OiPr)4.

Table 2. Influence of the ligand amount on the enantiomeric excess Entry 1 2 3 4 5 6

Ligand

Amount (equiv)

Concentration (mmol/ml)

Temperature (8C)

Time (h)

Yield (%)

ee (config.) (%)

1a 1a 1a 1a 1a 1a

0.2 0.2 0.4 0.6 0.8 1.0

0.034 0.044 0.044 0.054 0.064 0.074

22 22 22 22 22 22

20 18 18 18 18 18

88 95 88 89 85 80

77 (S) 78 (S) 79 (S) 81 (S) 81 (S) 80 (S)

Table 3. Influence of the reaction temperature on the enantiomeric excess Entry 1 2 3 4

Ligand

Temperature (8C)

Time (h)

Yield (%)

ee (config.) (%)

1a 1a 1a 1a

22 0 K20 K78

18 19 19 72

95 87 62 —

78 (S) 80 (S) 76 (S) —

Table 4. Optimalization of the complexation time with Ti(OiPr)4 Entry 1 2 3 4 5

Ligand

Amount (equiv)

Complexation time (h)

Reaction time (h)

Yield (%)

ee (config.) (%)

1a 1a 1a 1a 1a

0.2 0.2 0.2 0.2 0.2

0.5 1 1.5 2 2.5

18 18 18 18 18

90 94 95 87 90

77 (S) 78 (S) 78 (S) 78 (S) 77 (S)

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Table 5. Optimalization of the complexation time with Et2Zn Entry 1 2 3 4 5 6

Ligand

Amount (equiv)

Complexation time (h)

Reaction time (h)

Yield (%)

1a 1a 1a 1a 1a 1a

0.2 0.2 0.2 0.2 0.2 0.2

0.5 0.75 1 1.5 2 2.5

18 18 19 18 18 18

95 96 94 95 87 90

ee (config.) (%) 78 79 78 75 75 75

(S) (S) (S) (S) (S) (S)

Table 6. Optimalization of amounts of Et2Zn and Ti(OiPr)4 sufficient for the efficient addition Entry 1 2 3 4 5 6 7 8 9

Ligand

Amount of 1a (equiv)

Et2Zn (equiv)

Ti(OiPr)4 (equiv)

Time (h)

Yield (%)

ee (config.) (%)

1a 1a 1a 1a 1a 1a 1a 1a 1a

0.2 0.2 0.2 0.2 0.2 0.2 0.2 0.2 0.2

3 2.5 2 1.5 1 2 2 2 2

1.4 1.4 1.4 1.4 1.4 1.2 1 0.8 0.6

18 18 18 42 42 18 18 18 18

96 97 92 55 41 86 88 90 85

79 (S) 79 (S) 80 (S) 80 (S) 80 (S) 80 (S) 80 (S) 80 (S) 78 (S)

established, were amounts of diethylzinc and titanium tetraisopropoxide sufficient for the good chemical yield and asymmetric induction. The optimum was found to be 2 equiv of Et2Zn and 0.8 equiv of Ti(OiPr)4 (Table 6, entry 8). It is important to stress that substochiometric amounts of titanium are sufficient to produce S-3 in 90% yield and 80% ee. Having established all the important parameters of the reaction we carried out the enantioselective addition of diethylzinc to some representative aromatic and aliphatic aldehydes. As shown in the Table 7, for all but one aldehyde (cinnamaldehyde, entry 7) enantioselectivities were at levels comparable with that obtained for benzaldehyde, even for aliphatic and cycloaliphatic aldehydes (entries 8 and 9). 2.2.2. Enantioselective diethylzinc addition to aldehydes in the presence of various a-hydroxy acids. The positive results presented above prompted us to synthesize and use series of aromatic and aliphatic a-hydroxy acids with various steric demands. The results are presented in Table 8. The increased bulkiness of the acid substituent is reflected in the increased asymmetric induction. The individual character of each ligand means that conditions optimized for each one of them (e.g., mandelic acid 1a) are not good for others (entry 1 vs 2, 3 vs 4, 10 vs 11), so we decided to use ‘typical’ (widely used in the literature) conditions K3 equiv of diethylzinc and 1.4 equiv of titanium tetraisopropoxide. The best results were obtained for two ligands 1g and 1h. Interestingly, ligand 1i with more bulky isopropyl substituent, gave lower asymmetric induction than 1h. Also, in this study, the bulkiness of the titanium reagent (entry 5) had an adverse effect on the asymmetric induction. For relatively inexpensive and readily available ligand 1c the influence of ligand amount and its concentration on ee was established (Table 9). The increased amounts of ligand 1c gives slightly better enantiomeric excess but this effect is

accompanied by longer reaction time and a serious drop of chemical yield (entry 1 vs entries 2–5 in Table 9). The reaction performed at 0 8C gave somewhat higher ee (entry 6), but the reaction stops at lower temperatures (entries 7 and 8). The enantioselective addition of diethylzinc to some representative aromatic and aliphatic aldehydes was performed in the presence of ligand 1h, which was easy to obtain in high chemical and enantiomeric purity, despite its multistep synthesis. The results are presented in Table 10. In general, the results obtained in the presence of ligand 1h were better than in the presence of 1a, with the exception of aliphatic aldehydes 16 and 17 that gave substantially lower enantiomeric excess. 2.2.3. Mechanistic considerations. The stereochemical outcome of the reaction performed in the presence of ahydroxy acids can be rationalized as follows. The variation of the addition order of titanium and zinc reagents, leading to virtually identical asymmetric induction indicates a monometallic transition state, which has been postulated several times in the literature for other ligands.26,27 We suggest that the reaction goes through one of the possible model transition states I–III depicted in Figure 1. For picture simplicity, addition of diethylzinc to benzaldehyde in the presence of mandelic acid is analyzed. In the model I re attack leads to products with the absolute configuration R,

Figure 1. Stereochemical models for an ethylation of aldehydes.

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Table 7. Et2Zn addition to selected aldehydes in the presence of 1a Entry

1a (equiv)

Aldehyde

Temperature (8C)

Time (h)

Product

Yield (%)

ee (%)

1

0.2

9

28

19

S-18

75

76

2

0.2

10

28

18

S-19

90

70

3

0.2

11

28

19

S-20

97

72

4

0.2

12

28

19

S-21

88

79

5

0.2

13

28

19

S-22

97

77

6

0.2

14

28

18

S-23

96

80

7

0.2

15

28

17

S-24

91

52

8

0.2

16

28

17

S-25

75

78

9

0.2

17

28

19

S-26

81

77

opposite to that observed in experiments. In models II and III the si attack leads to the observed configuration, but the apical position of the bulky isopropoxy group in the model II is not very likely, due to a steric clash with the aryl (or alkyl) moiety of the a-hydroxy acid. The model transition

state III in our opinion is the best explanation of the observed asymmetric induction. In all three we postulate the presence of hydrogen bonding between ligand’s a-oxygen and formyl hydrogen of the coordinated aldehyde. Such bonding was already postulated by Corey, and was proved

Table 8. Addition of Et2Zn to benzaldehyde in the presence of acids 1b–i Entry

1 2 3 4 5a 6 7 8 9 10 11 12 a

Ligand

Amount of 1b–i (equiv)

Amount of Ti(OiPr)4 (equiv)

Amount of Et2Zn (equiv)

Time (h)

Yield (%)

Ee (config.) (%)

1b 1b 1c 1c 1c 1d 1e 1f 1g 1h 1h 1i

0.2 0.2 0.2 0.2 0.2 0.2 0.2 0.2 0.2 0.2 0.2 0.2

1.4 0.8 1.4 0.8 1.4 1.4 1.4 1.4 1.4 1.4 0.8 1.4

3 2 3 2 3 3 3 3 3 3 2 3

19 24 19 24 45 19 20 20 20 20 18 20

80 90 85 95 67 73 71 88 95 95 74 95

85 (S) 83 (S) 85 (S) 80 (S) 78 (S) 80 (S) 83 (S) 77 (S) 88 (S) 87 (S) 79 (S) 79 (S)

Ti(OtBu)4 instead of Ti(OiPr)4

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Table 9. Influence of ligand amount on the enantiomeric excess in the addition of Et2Zn to benzaldehyde Entry

Ligand

Amount (equiv)

Concentration (mmol/ml)

Temperature (8C)

Time (h)

Yield (%)

1c 1c 1c 1c 1c 1c 1c 1c

0.2 0.4 0.6 0.8 1.0 0.2 0.2 0.2

0.044 0.044 0.054 0.064 0.074 0.044 0.044 0.044

22 22 22 22 22 0 K23 K78

19 24 40 42 42 20 48 48

85 79 56 54 27 82 — —

1 2 3 4 5 6 7 8

to be a very important factor influencing asymmetric induction in enantioselective reactions.28 Its presence substantially rigidifies transition states leading to good enantiomeric excess.

3. Conclusions We have proposed a new class of chiral ligands applicable

ee (%) 85 87 88 91 88 86 — —

(S) (S) (S) (S) (S) (S)

to enantioselective additions of diethylzinc to aldehydes. We have shown that reactions in the presence of a-hydroxy acids proceed with very good yield and good enantiomeric excess up to 90%. a-Hydroxy acids can catalyze the addition of diethylzinc to both aliphatic and aromatic aldehydes, are relatively inexpensive and are readily available. Further applications of a-hydroxy acids as ligands for enantioselective metalloorganic additions are under investigation and will be reported in due course.

Table 10. Et2Zn addition to selected aldehydes in the presence of 1h Entry

Amount of 1h (equiv)

Aldehyde

Temperature (8C)

Time (h)

Product

Yield (%)

ee (%)

1

0.2

9

21

24

S-18

95

76

2

0.2

10

21

19

S-19

94

77

3

0.2

11

21

24

S-20

83

82

4

0.2

12

21

19

S-21

85

89

5

0.2

13

21

18

S-22

96

78

6

0.2

14

21

18

S-23

95

83

7

0.2

15

21

18

S-24

87

59

8

0.2

16

21

23

S-25

70

65

9

0.2

17

21

23

S-26

70

68

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4. Experimental

Tiny, colorless needles; yield 52% (0.69 g, 5.2 mmol). Mp 50–52 8C (ether–hexane) lit.29: 52–54 8C. [a]20 D ZC21.9 (cZ1, CHCl3); lit.31 [a]22 D ZC22 (cZ1, CHCl3).

Melting points were determined using a Kofler hot stage apparatus and are uncorrected. Specific rotations were recorded using a Perkin–Elmer PE-241 polarimeter with a thermally jacketed 10-cm cell. 1H and 13C NMR spectra were recorded in CDCl3 using a Varian 200 Unity Plus and Varian 500 Unity Plus spectrometers. All chemical shifts are quoted in parts per million relative to tetramethylsilane (d, 0.00 ppm), and coupling constants (J) are measured in Hertz. Mass spectra were recorded on a Mariner instrument (Biosystem) using the LSIMS technique. Infrared spectra were recorded using a Beckmann IR-240 spectrometer. Reactions were carried under argon using Schlenk technique when necessary. Flash column chromatography was made on silica gel (Kieselgel-60, Merck, 230–400 mesh). High Performance Liquid Chromatography was conducted on Merck Hitachi D-7000 with diode array detector L-7455 using chiral column Diacel Chiracel OD. Gas Chromatography was conducted on Hewlett–Packard 5890 series II with FID detector using chiral column b-Dex, 30 m! 0.25 mm I.D. (Supelco, Bellefonte, USA). Retention time is given in minutes.

4.2.5. (S)-2-Hydroxyhexanoic acid (1f). White crystals; yield 30% (0.40 g, 3.0 mmol). Mp 59–60 8C (ether–hexane) 33 lit.32: 60–61 8C. [a]20 D ZK16.3 (cZ3.92, 1 M NaOH); lit. [a]25 ZK15.3 (cZ1.1, 1 M NaOH). D

4.1. General

4.2. Preparation of a-hydroxy acids form a-amino acids by diazotisation. General procedure a-Amino acid (10 mmol) was dissolved in 0.5 M H2SO4 (40 mL, 20 mmol). This solution was cooled to 0 8C and a solution of NaNO3 (4.14 g, 60 mmol) in H2O (13.5 mL) was added slowly with stirring, while temperature was maintained below 5 8C. The reaction was stirred at this temperature for a further 3 h, and than allowed to warm up to room temperature and left for 24 h. The reaction mixture was extracted 3 times with ethyl ether (3!50 mL), combined organic layers were washed with brine (50 mL) and dried over anhydrous sodium sulfate. The drying agent was filtered off, and ether was evaporated in vacuo. The residual mass was recrystallized from hexane–ether to give respective a-hydroxy acid. All compounds have been previously reported and were characterized by comparison with their reported physical and spectroscopic data. 4.2.1. (S)-2-Hydroxy-3-phenylpropanoic acid (1b). Tiny, colorless needles with characteristic pleasant smell; yield 65% (1.08 g, 6.2 mmol). Mp 123–123 8C (ether–hexane); 29 lit.22 123–124 8C. [a]20 D ZK21.3 (cZ2.35, H2O); lit. [a]DZK20.0 (cZ2, H2O). 4.2.2. (S)-2-Hydroxy-3-methylbutanoic acid (1c). Tiny, colorless needles with intensive unpleasant smell; yield 31% (0.37 g, 3.1 mmol). Mp 61–62 8C (ether–hexane) lit.30 29 62–63 8C. [a] 20 D ZC17.3 (cZ1.06, CHCl 3 ); lit. [a]DZC17.3 (cZ1, CHCl3). 4.2.3. (S)-2-Hydroxy-4-methylpentanoic acid (1d). Colorless needles yield; 40% (0.53 g, 4.0 mmol). Mp 76–77 8C (ether–hexane) lit.22 78–80 8C. [a]20 D ZK26.6 (cZ1.2, 1 M NaOH); lit.29 [a]DZK25.9 (cZ1, 1 M NaOH). 4.2.4. (2S,3S)-2-Hydroxy-3-methylpentanoic acid (1e).

4.2.6. (S)-2-Hydroxy-3,3-dimethylbutanoic acid (1g). Small colorless crystals; yield 47% (0.62 g, 4.7 mmol). Mp 47–48 8C (ether–hexane) lit.34: 49–51 8C. [a]22 D ZC4.1 24 (cZ1.83, H2O); lit.23 [a]25 D ZC4.5 (cZ1, H2O); lit. 25 [a]D ZC4.5 (cZ4, H2O). 4.3. General procedure for the addition of diethylzinc to aldehyde in the presence (S)-mandelic acid In the oven dried Schlenk tube filled with argon and equipped with the stirring bar was placed (S)-mandelic acid (30.2 mg, 0.2 mmol), followed by methylene chloride (4.5 mL), Ti(OiPr)4 (0.24 mL, 0.8 mmol). After 1.5 h the solution was cooled to 0 8C and diethylzinc (1.1 M in toluene, 1.8 mL, 2 mmol) was added. The stirring was continued at this temperature for 45 min, aldehyde (1 mmol) was added and after additional 30 min of stirring at 0 8C the reaction mixture was allowed to warm up to room temperature. The progress of the reaction was controlled with TLC using CH2Cl2:MeOH 70:2. After completion the reaction was quenched with slow addition of 1 M HCl (CAUTION! Exothermic reaction). The precipitate was filtered off using funnel with cotton plug and filtrate was extracted three times with ethyl acetate (3!20 mL), combined extracts were washed with brine (30 mL), dried over anhydrous MgSO4 and evaporated in vacuo. The resulting oil was purified by flash chromatography (CH2Cl2/MeOH 200:3 as eluent). All compounds have been previously reported and were characterized by comparison with their reported physical and spectroscopic data. 4.3.1. (S)-1-Phenyl-1-propanol (S-3). HPLC: tSZ12.1 tRZ13.2 (hexane/iPrOH 97:3, flow 1 mL/min). [a]20 DZ K42.0 (cZ1.0, CHCl3); for enantiomer S with eeZ90.4%. lit.35 [a]20 D ZK44.4 (cZ1.01, CHCl3) for enantiomer S with eeZ95.5%. 4.3.2. (S)-1-(2-Chlorophenyl)-1-propanol (S-18). GC: t RZ51.0, t SZ54.2 (TcolumnZ130 8C, PZ100 kPa). [a]20 D ZK48.6 (cZ1.25, benzene) for eeZ85%. 4.3.3. (S)-1-(3-Chlorophenyl)-1-propanol (S-19). HPLC: tSZ17.1 tRZ18.6 (hexane/iPrOH 96:4, flow 0.5 mL/min). [a]20 D ZK23.3 (cZ1.21, benzene) for enantiomer S with eeZ78.8%. lit.36 [a]20 D ZC26.6 (cZ2.36, benzene) for enantiomer R with eeZ97%. 4.3.4. (S)-1-(4-Chlorophenyl)-1-propanol (S-20). HPLC: tSZ22.4 tRZ24.3 (hexane/iPrOH 97:3, flow 0.5 mL/min). [a]20 D ZK23.6 (cZ1.77, benzene) for enantiomer S with eeZ88.5%. lit.35 [a]20 D ZK23.6 (cZ1.73, benzene) for enantiomer S with eeZ93%.

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4.3.5. (S)-1-(2-Metoxyphenyl)-1-propanol (S-21). HPLC: tSZ27.5 tRZ29.6 (hexane/iPrOH 97:3, flow 0.5 mL/min). [a]20 D ZK50.8 (cZ1.22, toluene) for enantiomer S with eeZ89.1%. lit.35 [a]22 D ZK52.9 (cZ1.02, toluene) for enantiomer S with eeZ91%. 4.3.6. (S)-1-(3-Metoxyphenyl)-1-propanol (S-22). HPLC: tSZ80.3 tRZ76.6 (hexane/iPrOH 97:3, flow 0.3 mL/min). [a]20 D ZK26.8 (cZ0.8, toluene)) for enantiomer S with eeZ 92%. 4.3.7. (S)-1-(4-Metoxyphenyl)-1-propanol (S-23). HPLC: tSZ38.1 tRZ33.6 (hexane/:iPrOH 97:3, flow 0.5 mL/min). [a]20 D ZK28.7 (cZ1, benzene)) for enantiomer S with eeZ 83%. lit.35 [a]20 D ZK25.8 (cZ1.1, benzene) for enantiomer S with eeZ74%. 4.3.8. (S)-1-Phenyl-1-penten-3-ol (S-24). HPLC: tSZ13.0 tRZ9.0 (hexane/iPrOH 90:10, flow 1.0 mL/min). [a]20 DZ K4.87 (cZ1, CHCl3) for enantiomer S with eeZ63%. lit.14 [a]20 D ZK6.3 (cZ1.73, CHCl3) for enantiomer S with eeZ 59%. 4.3.9. (S)-3-Octanol (S-25). HPLC (as benzoate): tSZ21.1 tRZ23.1 (hexane, flow 0.5 mL/min). [a]20 D ZC7.6 (cZ 1.03, CHCl3); for enantiomer S with eeZ77%. lit.35 [a]20 D ZC5.87 (cZ1, CHCl3), for enantiomer S with eeZ 60%. 4.3.10. (S)-1-Cyclohexyl-1-propanol (S-26). HPLC (as benzoate): tSZ37.8 tRZ35.9 (hexane/iPrOH 99.9:0.1, flow 0.2 mL/min). [a]20 D ZK5.43 (cZ1.14, CHCl3) for enantiomer S with eeZ82.5%. lit.35 [a]24 D ZK6.39 (cZ1.05, CHCl3), for enantiomer S with eeZ97%. Acknowledgements Financial support from the State Committee for Scientific Research (Grant 3 T09A 039 16) is gratefully acknowledged.

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