t BuOLi-Promoted Hydroboration of Esters and Epoxides.

Commercially available and inexpensive lithium tert-butoxide ( t BuOLi) acts as a good precatalyst for the hydroboration of esters, lactones, and epoxides using pinacolborane as a borylation agent. Functional groups such as cyano-, nitro-, amino-, vinyl, and alkynyl are unaffected under the presented hydroboration process, representing high chemoselectivity. This transformation has also been effectively applied to the synthesis of key intermediates of Erlotinib and Cinacalcet. Preliminary investigations of the mechanism show that the hydroboration proceeds through the in situ formed BH3 species.

Introduction

The reduction of esters to alcohols is a fundamental transformation in organic chemistry for the production of a wide range of bulk and fine chemicals. The typical reduction reagents of esters include metal hydride compounds such as LiAiH4, NaBH4, NaH, and KH. However, major drawbacks include poor functional group tolerance, the formation of stoichiometric amounts of metallic waste, the need for laborious workup procedures for metal alkoxide intermediates, and the hazards involved in handling these highly reactive substances, which have hampered their development.[1] Catalytic hydrogenation of esters employing H2 constitutes a completely atom-economic, waste-free, and environmentally benign transformation. However, it requires the use of flammable hydrogen gas under harsh reaction conditions such as high reaction temperature and pressure and/or costly dedicated catalysts.[2] The demanding conditions, along with frequent selectivity issues, strongly limit its synthetic applicability in the reduction of ester derivatives. Complementary to direct hydrogenation with molecular hydrogen, the transfer hydrogenation of esters using hydrogen donors such as alcohol is gaining a lot of attention because of its safety and operational simplicity. In this regard, several transition-metal-catalyzed transfer hydrogenations of esters have been reported.[3] The de Vries, Khaskin, Nikonov, and Clarke research groups independently developed transition-metal-catalyzed transfer hydrogenation of esters with cationic half-sandwich Ru complexes,[3a] Ru-SNS,[3b] Fe-PNP pincer complexes,[3c] and Mn-PNN pincer complexes.[3d] In addition, hydroelementation of unsaturated systems is becoming an issue of increasing importance to scientists.[4] Among them, catalytic hydrosilylation of esters has been extensively explored, with esters smoothly converted into the corresponding alcohol under catalysis with titanium,[5] iridium,[6] znic,[7] ruthenium,[8] manganese,[9] and iron.[10] Although each approach has merits, many of these hydrosilylation methods are offset by the requirement of excessive high-cost and air-sensitive silanes such as PhSiH3, which has adversely affected the application of these strategies. Compared with silanes, organoboranes are nontoxic; thus, they have become a preferable hydride choice. In contrast to the aforementioned ester hydrosilylation approaches, very limited examples regarding metal-catalyzed hydroboration of esters have been reported. Sadow et al. reported that the magnesium catalyst ToMMgMe (ToM = tris(4,4-dimethyl-2-oxazolinyl)phenylborate) rapidly and efficiently catalyzed ester hydroboration via an ester cleavage zwitterionic reaction pathway.[11] Subsequently, Nembenna’s group revealed the efficient hydroboration of esters using magnesium complexes bearing N,N′-chelated guanidinate and terminal amido ligands as a catalyst.[12] Next, homoleptic lanthanum complexes such as La[N(SiMe3)2]3 and La[C(SiHMe2)3]3 were independently reported as efficient precatalysts for the hydroboration of a wide range of esters by the Marks, Sadow, and Xue groups.[13] Findlater found that the efficient hydroboration of esters could be realized using polynuclear lanthanide–diketonato clusters.[14] Recently, Eisen reported an efficient hydroboration of esters promoted by the thorium and uranium amide complexes U[N(SiMe3)2]3 and [(Me3Si)2N]2An[κ2-(N,C)-CH2Si(CH3)2N(SiMe3)] (An = Th or U).[15] Owing to the complex nature of the reported ester hydroboration catalysts, these protocols have much room for improvement, particularly in terms of easily achieved simple catalysts and workup procedure.

Lithium compounds are frequently used in the dye, pigment, and pharmaceutical industries in preference to transition- or lanthanide-metal complexes.[16] Moreover, because most of the metal complexes are commonly prepared from the corresponding lithium reagents, direct use of lithium species in catalytic transformations would obviate the need for such additional synthesis of lithium reagents. The Sen group reported the efficient hydroboration of esters using two well-defined lithium complexes, 2,6-di-tert-butyl phenolate lithium and 1,1′-dilithioferrocene.[17] Recently, the Ding group reported the hydroboration of esters using a super hydride, LiHBEt3.[18] Apart from the aforementioned work, ester is the sole example of substrates that have been sporadically reported.[19] However, many of the reported lithium-catalyzed ester hydroboration protocols are marred by complexity and uncommercialized lithium catalysts. Recently, the hydroboration of unsaturated systems has been applied in synthetic solutions using main-group compounds as catalysts, as well as on catalyst-free approaches.[20] An’s research group developed an efficient transition-metal-free protocol for the hydroboration of carbonyl and alkene functionalities.[21a] Hreczycho and co-workers reported that hydroboration of carbonyl compounds could be achieved in the presence of potassium fluoride.[21b] Zhao et al. showed that catalytic hydroboration of nonpolarized unsaturated compounds, such as alkenes, could be carried out in the presence of NaOH as a precatalyst.[21c] In this study, based on our previous hydroboration studies,[22] we herein present the results of our research on the catalytic hydroboration of esters and epoxides with simple BuOLi and HBpin.

Results and Discussion

To optimize the reaction conditions for this BuOLi-promoted ester hydroboration process, we selected methyl benzoate 1a and pinacolborane as model reaction substrates. To our pleasure, the corresponding product 2a was obtained in 32% yield after base workup when this reaction was conducted with Li2CO3 (10 mol %) in 1,4-dioxane at 100 °C for 24 h (Table , entry 1). Subsequently, the reaction conditions were optimized using different lithium catalysts, such as LiOCH3, BuOLi, and lithium bis(trimethylsilyl)amide (LiHMDS), where BuOLi and LiHMDS were found to give better results (Table , entries 2–4). Furthermore, NaHMDS and KHMDS were investigated, showing poor catalytic performance (Table , entries 5–6). The reaction could not work well when the catalyst was absent (Table , entry 7). When the catalyst loadings of BuOLi and LiHMDS were reduced to 5 mol %, the yield of 2a decreased to 83 and 80%, respectively (Table , entries 8–9). Next, the reaction conditions were optimized using different solvents, and THF was found to give the best result (Table , entries 10–13). We also studied the influence of the reaction temperature on this ester hydroboration process and found that 100 °C was the optimal reaction temperature (Table , entries 14–15). The yield of 2a decreased to 82% when 2.2 equiv of HBpin was used (Table , entry 16). The yield of 2a decreased to 79% while the reaction was performed in 18 h (Table , entry 17). Therefore, the optimal reaction conditions can be summarized as follows: 0.4 mmol of methyl benzoate and 1.0 mmol of HBpin in THF (1.0 mL) with BuOLi catalyst (5 mol %), at 100 °C for 24 h.

Table 1

Optimization of Reaction Conditionsa

entry	catalyst (x mol %)	solvent	T (°C)	yield (%)
1	Li2CO3 (10 mol %)	1,4-dioxane	100	32
2	LiOCH3 (10 mol %)	1,4-dioxane	100	81
3	tBuOLi (10 mol %)	1,4-dioxane	100	86
4	LiHMDS (10 mol %)	1,4-dioxane	100	85
5	KHMDS (10 mol %)	1,4-dioxane	100	14
6	NaHMDS (10 mol %)	1,4-dioxane	100	17
7		1,4-dioxane	100	trace
8	tBuOLi (5 mol %)	1,4-dioxane	100	83
9	LiHMDS (5 mol %)	1,4-dioxane	100	80
10	tBuOLi (5 mol %)	toluene	100	76
11	tBuOLi (5 mol %)	hexane	100	78
12	tBuOLi (5 mol %)	DCE	100	81
13	tBuOLi (5 mol %)	THF	100	90
14	tBuOLi (5 mol %)	THF	80	71
15	tBuOLi (5 mol %)	THF	60	46
16b	tBuOLi (5 mol %)	THF	100	82
17c	tBuOLi (5 mol %)	THF	100	79

Reactions were conducted using 1a (0.4 mmol), HBpin (1.0 mmol) in 1.0 mL of solvent under N2 atmosphere for 24 h. The yield was determined by 1H NMR spectroscopy of the crude product after base workup with 1,3,5-trimethoxybenzene as an external standard.

2.2 equiv of HBpin was used.

18 h.

With the optimal conditions in hand, the substrate scope of the BuOLi-promoted hydroboration of esters was explored. As shown in Scheme , a series of substituted methyl benzoates were tested and the reaction exhibited good functional group tolerance. The influence of substitutions on the aryl ring was investigated first. The electronic effect of the substituents affected the yields of this transformation to some extent. For example, when esters bearing an electron-donating para-methoxyl group on the phenyl ring were examined, 2e was obtained in a lower yield of 52% compared to those substrates with alkyl-containing groups attached to the aryl ring (2b–2f), respectively. Electron-withdrawing groups, such as fluoro, chloro, bromo, iodo, and trifluoromethyl on the phenyl ring, were well tolerated in this transformation, affording the desired alcohol products 2g–2o in a higher yield, ranging from 84 to 96%. Functional groups, such as naphthyl and biphenyl, were also tolerated with observed yields of 2p and 2q in 97 and 93%, respectively. Next, aliphatic esters with alpha hydrogens (e.g., 1r–1u) were also successfully transformed to target products 2r–2u when subjected to the reaction conditions in moderate to good yield, ranging from 52 to 92%, with no Claisen condensation products formed, representing good chemoselectivity of the current catalytic system. To our delight, heteroaromatics such as furan, thiophene, and pyridine were found to be compatible, reaching 90% conversion with 10 mol % BuOLi catalyst (2v–2x). It is worth noting that one of the major drawbacks of catalytic hydrogenations of esters is the low selectivity in the presence of additional unsaturated bonds. When we manage challenging substrates that might undergo additional hydroboration transformations, the additional cyano, nitro, C=C double bonds, and C≡C triple bonds remained intact, with only the ester group reacted (2y–2zc), representing high chemoselectivity of the BuOLi catalytic system. To our delight, the catalytic system is effective for the transformation of amino-containing esters (2zd–2ze). In contrast, amino boranes can be easily formed via dehydrocoupling coupling reactions between the boranes and HBpin in the presence of alkaline-earth and alkali-metal catalysts,[23] and the amino group is usually incompatible in hydroboration reactions. Finally, when R2 is equal with ethyl, phenyl, 4-chlorophenyl, and vinyl, these benzoates (1a-1-1a-4) were also well compatible in current transformation, affording the desired product 2a in 81–91% isolated yield.

Scheme 1

Scope of the BuOLi-Promoted Hydroboration of Esters,

All of the experiments were carried out with 1 (1.0 mmol), HBpin (2.5 mmol), BuOLi (5 mol %), THF (1.0 mL), 100 °C, N2, 24 h, isolated yield after base workup.

BuOLi (10 mol %).

Other borylation agents such as catecholborane and 1,8-naphthalenediaminatoborane instead of HBpin were also tested under the current reaction conditions, affording the desired product 2a in 17–48% yield, respectively. The hydroboration of methyl benzoate failed when 9-borabicyclo[3.3.1]nonane was used as the borylation agent (Scheme ).

Scheme 2

Scope of the Borylation Agent

All of the experiments were carried out with 1 (1.0 mmol), borylation agent (2.5 mmol), BuOLi (5 mol %), THF (1.0 mL), 100 °C, N2, 24 h, isolated yield after base workup.

We next focused our attention on the reduction of lactones. Selective formation of diols was achieved from lactones with HBpin, as shown in Scheme . The δ-lactone 6-propyltetrahydro-2H-pyran-2-one (1zf) and β,γ-lactone 5-butyl-4-methyldihydrofuran-2(3H)-one (1zg) were fully converted into the corresponding nonane-1,5-diol (2zf) and 3-methyloctane-1,4-diol (2zg). Notably, isochroman-3-one (1zh) was converted selectively into 2-(2-(hydroxymethyl)phenyl)ethanol (2zh), which was isolated in 89% yield. Similarly, with isobenzofuran-1(3H)-one (1zi) as the starting substrate, 1,2-phenylenedimethanol (2zi) was obtained in 86% yield.

Scheme 3

Scope of the BuOLi-Promoted Hydroboration of Lactones

All of the experiments were carried out with lactones (1.0 mmol), HBpin (2.5 mmol), BuOLi (10 mol %), THF (1.0 mL), 100 °C, N2, 24 h, isolated yield after base workup.

On the basis of the high catalytic hydroboration reactivity of BuOLi toward esters and lactones, we next investigated the ring-opening of epoxides to alcohols, which would also involve a C–O bond-cleavage step. As expected, BuOLi is an active catalyst for this process, affording desired alcohol compounds 2zj–2zn in high yields (Scheme ).

Scheme 4

Scope of the BuOLi-Promoted Hydroboration of Epoxides

All of the experiments were carried out with epoxide (1.0 mmol), HBpin (2.5 mmol), tBuOLi (5 mol %), THF (1.0 mL), 100 °C, N2, 24 h, isolated yield.

To show the scalability of this protocol, methyl 4-chlorobenzoate (1h) and HBpin were used at the gram scale (Scheme a). Pure (4-chlorophenyl)methanol 2h was isolated in 91% yield (1.292 g). To demonstrate further the utility of our developed methodology in drug synthesis, some extended work was conducted. First, the key intermediate of tyrosine kinase inhibitor Erlotinib 2zo-1 was synthesized from the corresponding ester 1zo through a two-step process in 50% overall yield (Scheme b). Furthermore, the utility of the current methodology was applied to the synthesis of 3-(3-(trifluoromethyl)phenyl)propan-1-ol (2zp), which is the key intermediate of therapeutic agent Cinacalcet 2zp-1 (Scheme c).[24]

Scheme 5

Gram-Scale Transformation and Applications of the Developed Method for Biologically Active Molecules Synthesis

To gain insight into the mechanism of the reaction, some control experiments were performed. First, 1H NMR spectra for the progress of the model reaction were investigated and 1a was cleanly converted into the corresponding hydroboration product benzylOBpin (Figure ). According to the reported results, the hydroboration process is plagued by Trojan horse/hidden catalysis.[25] An’s research group has shown that potassium carbonate acts as a catalyst in the hydroboration of carbonyl compounds reactions.[21a] Thomas and co-workers found that nucleophiles could promote the decomposition of HBpin to release BH3.[26] The reaction of HBpin with a catalytic amount of BuOLi together with SMe2 in benzene-d6 at 100 °C for 30 min was performed to identify potential substrate–precatalyst complexes or catalyst intermediates with the aid of 11B NMR spectroscopy. The 11B NMR spectrum showed weak 11B signals at −13.50, −20.67, and −39.83 ppm (see Supporting Information Figure S1). The resonances at −13.50 and −20.67 ppm stem from BH3 and BH3·SMe2, respectively, whereas the −39.83 ppm signal most likely arises from the BH4– anion.[26a] This result of 11B NMR spectroscopy shows that BH3 was formed in situ. The same control experiments were also carried out for the other borylation agents with tBuOLi together with SMe2, monitored by 11B NMR (see Supporting Information Figures S2–S4). No BH3 species were formed when 9-borabicyclo[3.3.1]nonane was used as the borylation agent. The BH3 was also found to be efficient reagent and catalyst for ester hydroboration (Scheme a,b). N,N,N′,N′-Tetramethylethylenediamine (TMEDA) could form air- and moisture-stable mono- and bis-adducts with BH3.[26c] To distinguish whether the in situ formed BH3 species acts as a real catalyst to drive the reaction, the BuOLi-promoted hydroboration reaction of methyl benzoate with TMEDA was further performed (Table ). The addition of TMEDA significantly inhibited the hydroboration process, indicating that the in situ formed BH3 species was the key intermediate to drive the reaction. Finally, the ester hydroboration reaction failed to deliver the desired product 2a when the BuOLi was absent (Scheme c), indicating that the BuOLi could promote the decomposition of HBpin to BH3 species.

Figure 1

1H NMR spectra for the progress of the reaction of 1a and HBpin using BuOLi as a precatalyst in benzene-d6 at 100 °C.

Scheme 6

Mechanistic Studies

Table 2

Inhibition of Ester Hydroboration by TMEDA

entry	TMEDA: tBuOLi	yield of 2a (%)
1a	0:1	92
2a	2:1	78
3a	5:1	59
4a	20:1	0
5b	0:1	89
6b	5:1	47
7b	9:1	18

Conditions: 1a (1.0 mmol), BuOLi (0.05 mmol), HBpin (2.5 mmol), 100 °C, THF (1 mL), TMEDA, N2, isolated yield.

Conditions: 1a (1.0 mmol), BuOLi (0.4 mmol), HBpin (2.5 mmol), room temperature, solvent-free, TMEDA, N2, isolated yield.

Conclusions

A general and practical BuOLi-promoted hydroboration of esters has been developed. Furthermore, lactones and epoxides underwent direct hydroboration with HBpin to give the desired alcohol products in synthetically useful yield after basic workup. Utilizing this low-toxicity, commercially available, and low-cost BuOLi as the initiator instead of environmentally unfriendly transition metals is the salient feature of this system. Coupled with its remarkable substrate tolerance, high chemoselectivity, and good yields, this method will be appealing for organic synthesis. Practical applications were demonstrated in a large-scale synthesis. This transformation has also been effectively applied to the synthesis of key intermediates of Erlotinib and Cinacalcet. Preliminary investigations of the mechanism show that the hydroboration proceeds through the in situ formed BH3 species. We believe this catalytic process to be very user-friendly, and we are investigating the use of this system in other reduction processes.

Experimental Section

General Methods

All hydroboration reactions were carried out under a moisture- and oxygen-free nitrogen atmosphere. 1,4-Dioxane, 1,2-dichloroethane (DCE), toluene, hexane, and tetrahydrofuran (THF) were taken from a solvent purification system (PS-400-5, Unilab Mbraun, Inc.). Glassware was predried in an oven at 100 °C for several hours and cooled prior to use. BuOLi, esters, lactones, and epoxides were obtained commercially from Energy Chemical, J&K, Acros Organics, Alfa Aesar, or TCI without further purification. Melting points are uncorrected and recorded on Digital Melting Point Apparatus WRS-1B. Compounds 1zp, 2zo-1, and HBdan were synthesized according to ref (24). Deuterated solvents were obtained from Cambridge Isotope. 1H NMR, 13C NMR, and 11B NMR spectra were recorded on a JEOL ECA-500 NMR spectrometer (FT, 500 MHz for 1H; 125 MHz for 13C; 160 MHz for 11B) at room temperature. All chemical shift values are quoted in ppm referenced to an internal tetramethylsilane at 0.00 ppm for 1H NMR and relative to residual CHCl3 at 77.16 ppm for 13C unless otherwise noted. The following abbreviations were used to describe peak splitting patterns when appropriate: br = broad, s = singlet, d = doublet, t = triplet, q = quartet, m = multiplet. Coupling constant (J) was reported in hertz. GC-MS analyses were measured on a Focus GC-ISQ MS instrument.

General Procedure for BuOLi-Promoted Hydroboration of Esters

In a nitrogen-filled glovebox, to a 10 mL Schlenk reaction tube equipped with a magnetic stirrer, BuOLi (4.0 mg, 5 mol %), THF (1.0 mL), HBpin (320.0 mg, 2.5 mmol), and the corresponding esters (1 mmol) were added in sequence. The reaction mixture was then heated at 100 °C (oil bath) with vigorous stirring for 24 h. Thereafter, the reaction mixture was cooled down to room temperature and NaOH/MeOH (2 mL, 10% aq.) solution was added. The resulting mixture was stirred overnight for complete hydrolysis. Organic compounds were extracted from the mixture with CH2Cl2 (3 × 12 mL). The organic fraction was dried over Na2SO4, and all volatiles were removed using a rotary evaporator. The crude mixture was monitored by 1H NMR analysis using hexamethylbenzene or 1,3,5-trimethoxybenzene as the internal standard. The crude mixture was purified by flash column chromatography using PE/EtOAc (10/1) as the eluent to give the corresponding products.

Benzyl Alcohol (2a)

Purified by column chromatography using petroleum ether/EtOAc = 10:1 as eluent. Obtained as a colorless oil (97.2 mg, 90%). 1H NMR (500 MHz, CDCl3) δ 7.37–7.36 (m, 4H), 7.32–7.28 (m, 1H), 4.67 (s, 2H), 2.01 (s, 1H). 13C{1H} NMR (125 MHz, CDCl3) δ 141.0, 128.7, 127.8, 127.1, 65.4. Spectroscopic data for the title compound were consistent with those reported in the literature.[2d]

4-Methylbenzyl Alcohol (2b)

Purified by column chromatography using petroleum ether/EtOAc = 10:1 as eluent. Obtained as a white soild (107.4 mg, 88%), mp 61–62 °C. 1H NMR (500 MHz, CDCl3) δ 7.24 (d, J = 7.6 Hz, 2H), 7.16 (d, J = 7.7 Hz, 2H), 4.62 (s, 2H), 2.34 (s, 3H), 1.82 (s, 1H). 13C{1H} NMR (125 MHz, CDCl3) δ 138.1, 137.5, 129.4, 127.2, 65.4, 21.2. Spectroscopic data for the title compound were consistent with those reported in the literature.[3a]

4-tert-Butylbenzyl Alcohol (2c)

Purified by column chromatography using petroleum ether/EtOAc = 10:1 as eluent. Obtained as a colorless oil (142.7 mg, 87%). 1H NMR (500 MHz, CDCl3) δ 7.40 (d, J = 8.4 Hz, 2H), 7.31 (d, J = 8.5 Hz, 2H), 4.65 (s, 2H), 2.00 (brs, 1H), 1.34 (m, 9H). 13C{1H} NMR (125 MHz, CDCl3) δ 150.8, 138.1, 127.0, 125.6, 65.2, 34.7, 31.5. Spectroscopic data for the title compound were consistent with those reported in the literature.[27a]

2-Methylbenzyl Alcohol (2d)

Purified by column chromatography using petroleum ether/EtOAc = 10:1 as eluent. Obtained as a colorless oil (112.2 mg, 92%). 1H NMR (500 MHz, CDCl3) δ 7.36–7.34 (m, 1H), 7.23–7.19 (m, 3H), 4.67 (s, 2H), 2.35 (s, 3H), 2.08 (s, 1H). 13C{1H} NMR (125 MHz, CDCl3) δ 138.8, 136.2, 130.4, 127.8, 127.6, 126.1, 63.5, 18.7. Spectroscopic data for the title compound were consistent with those reported in the literature.[6a]

4-Methoxybenzyl Alcohol (2e)

Purified by column chromatography using petroleum ether/EtOAc = 10:1 as eluent. Obtained as a colorless oil (106.3 mg, 77%). 1H NMR (500 MHz, CDCl3) δ 7.26 (d, J = 8.1 Hz, 2H), 6.87 (d, J = 7.7 Hz, 2H), 4.57 (s, 2H), 3.79–3.78 (m, 3H), 2.15 (s, 1H). 13C{1H} NMR (125 MHz, CDCl3) δ 159.2, 133.3, 128.7, 114.0, 64.9, 55.4. Spectroscopic data for the title compound were consistent with those reported in the literature.[2d]

2-Methoxybenzyl Alcohol (2f)

Purified by column chromatography using petroleum ether/EtOAc = 10:1 as eluent. Obtained as a colorless oil (117.3 mg, 85% yield). 1H NMR (500 MHz, CDCl3) δ 7.27–7.25 (m, 2H), 6.95–6.92 (m, 1H), 6.87 (d, J = 8.5 Hz, 1H), 4.66 (s, 2H), 3.83 (s, 3H), 2.58 (s, 1H). 13C{1H} NMR (125 MHz, CDCl3) δ 157.5, 129.2, 129.0, 128.8, 120.7, 110.3, 61.9, 55.3. Spectroscopic data for the title compound were consistent with those reported in the literature.[3d]

4-Fluorobenzyl Alcohol (2g)

Purified by column chromatography using petroleum ether/EtOAc = 10:1 as eluent. Obtained as a colorless oil (114.7 mg, 91%). 1H NMR (500 MHz, CDCl3) δ 7.33–7.32 (m, 2H), 7.05–7.02 (m, 2H), 4.63 (s, 2H), 2.03 (s, 1H). 13C{1H} NMR (125 MHz, CDCl3) δ 163.5, 161.5, 136.8 (d, J = 3.1 Hz), 128.9 (d, J = 8.1 Hz), 115.5 (d, J = 21.4 Hz), 64.7. Spectroscopic data for the title compound were consistent with those reported in the literature.[3c]

4-Chlorobenzyl Alcohol (2h)

Purified by column chromatography using petroleum ether/EtOAc = 10:1 as eluent. Obtained as a white solid (133.5 mg, 94%), mp 74–75 °C. 1H NMR (500 MHz, CDCl3) δ 7.32 (d, J = 8.4 Hz, 2H), 7.27 (d, J = 8.4 Hz, 2H), 4.63 (s, 2H), 2.11 (s, 1H). 13C{1H} NMR (125 MHz, CDCl3) δ 139.4, 133.5, 128.8, 128.4, 64.6. Spectroscopic data for the title compound were consistent with those reported in the literature.[2d]

4-Bromobenzyl Alcohol (2i)

Purified by column chromatography using petroleum ether/EtOAc = 10:1 as eluent. Obtained as a white solid (178.6 mg, 96%), mp 76–77 °C. 1H NMR (500 MHz, CDCl3) δ 7.47 (d, J = 8.2 Hz, 2H), 7.22 (d, J = 8.1 Hz, 2H), 4.62 (s, 2H), 2.03 (brs, 1H). 13C{1H} NMR (125 MHz, CDCl3) δ 139.9, 131.8, 128.7, 121.6, 64.6. Spectroscopic data for the title compound were consistent with those reported in the literature.[3d]

4-Iodobenzyl Alcohol (2j)

Purified by column chromatography using petroleum ether/EtOAc = 10:1 as eluent. Obtained as a white solid (222.3 mg, 95%), mp 71–72 °C. 1H NMR (500 MHz, CDCl3) δ 7.65 (d, J = 8.1 Hz, 2H), 7.05 (d, J = 8.0 Hz, 2H), 4.56 (s, 2H), 2.60 (s, 1H). 13C{1H} NMR (125 MHz, CDCl3) δ 140.5, 137.6, 128.9, 93.0, 64.5. Spectroscopic data for the title compound were consistent with those reported in the literature.[3d]

3-Chlorobenzyl Alcohol (2k)

Purified by column chromatography using petroleum ether/EtOAc = 10:1 as eluent. Obtained as a colorless oil (119.3 mg, 84%). 1H NMR (500 MHz, CDCl3) δ 7.30 (s, 1H), 7.24–7.21 (m, 2H), 7.17 (d, J = 6.5 Hz, 1H), 4.59 (s, 2H), 2.60 (s, 1H). 13C{1H} NMR (125 MHz, CDCl3) δ 142.9, 134.5, 129.9, 127.7, 127.0, 124.9, 64.5. Spectroscopic data for the title compound were consistent with those reported in the literature.[9b]

3-Bromobenzyl Alcohol (2l)

Purified by column chromatography using petroleum ether/EtOAc = 10:1 as eluent. Obtained as a colorless oil (173.0 mg, 93%). 1H NMR (500 MHz, CDCl3) δ 7.49 (s, 1H), 7.40 (d, J = 7.6 Hz, 1H), 7.25–7.19 (m, 2H), 4.61 (s, 2H), 2.53 (s, 1H). 13C{1H} NMR (125 MHz, CDCl3) δ 143.2, 130.7, 130.2, 130.0, 125.4, 122.7, 64.4. Spectroscopic data for the title compound were consistent with those reported in the literature.[27a]

2-Chlorobenzyl Alcohol (2m)

Purified by column chromatography using petroleum ether/EtOAc = 10:1 as eluent. Obtained as a colorless oil (120.7 mg, 85%). 1H NMR (500 MHz, CDCl3) δ 7.47 (d, J = 7.3 Hz, 1H), 7.36–7.35 (m, 1H), 7.29–7.22 (m, 2H), 4.77 (s, 2H), 2.18 (brs, 1H). 13C{1H} NMR (125 MHz, CDCl3) δ 138.3, 132.9, 129.5, 129.0, 128.9, 127.1, 62.9. Spectroscopic data for the title compound were consistent with those reported in the literature.[6a]

2-Bromobenzyl Alcohol (2n)

Purified by column chromatography using petroleum ether/EtOAc = 10:1 as eluent. Obtained as a white solid (165.5 mg, 89%), mp 78–79 °C. 1H NMR (500 MHz, CDCl3) δ 7.54 (d, J = 8.0 Hz, 1H), 7.47 (d, J = 7.6 Hz, 1H), 7.34–7.31 (m, 1H), 7.17–7.14 (m, 1H), 4.73 (s, 2H), 2.33 (s, 1H). 13C{1H} NMR (125 MHz, CDCl3) δ 139.9, 132.7, 129.2, 129.0, 127.8, 122.7, 65.1. Spectroscopic data for the title compound were consistent with those reported in the literature.[2a]

4-(Trifluoromethyl)benzyl Alcohol (2o)

Purified by column chromatography using petroleum ether/EtOAc = 10:1 as eluent. Obtained as a colorless oil (161.9 mg, 92%). 1H NMR (500 MHz, CDCl3) δ 7.60 (d, J = 7.9 HZ, 2H), 7.45 (d, J = 7.9 Hz, 2H), 4.73 (s, 2H), 2.30 (s, 1H). 13C{1H} NMR (125 MHz, CDCl3) δ 144.9, 130.2 (q, J = 32.4 Hz), 127.0, 125.6 (q, J = 3.7 Hz), 123.2, 64.6. Spectroscopic data for the title compound were consistent with those reported in the literature.[2d]

2-Naphthalenemethanol (2p)

Purified by column chromatography using petroleum ether/EtOAc = 10:1 as eluent. Obtained as a white solid (153.3 mg, 97%), mp 79–80 °C. 1H NMR (500 MHz, CDCl3) δ 7.85–7.84 (m, 3H), 7.80 (s, 1H), 7.50–7.47 (m, 3H), 4.85 (s, 2H), 2.00 (s, 1H). 13C{1H} NMR (125 MHz, CDCl3) δ 138.5, 133.5, 133.1, 128.5, 128.0, 127.8, 126.3, 126.0, 125.6, 125.3, 65.6. Spectroscopic data for the title compound were consistent with those reported in the literature.[3d]

[1,1′-Biphenyl]-4-ylmethanol (2q)

Purified by column chromatography using petroleum ether/EtOAc = 3:1 as eluent. Obtained as a white solid (171.1 mg, 93%), mp 99–100 °C. 1H NMR (500 MHz, CDCl3) δ 7.61 (d, J = 7.4 Hz, 4H), 7.48–7.44 (m, 4H), 7.39–7.36 (m, 1H,), 4.73 (s, 2H), 2.20 (s, 1H). 13C{1H} NMR (125 MHz, CDCl3) δ 140.9, 140.7, 140.0, 128.9, 127.6, 127.4 (d, J = 4.2 Hz), 127.2, 65.1. Spectroscopic data for the title compound were consistent with those reported in the literature.[27b]

3-Phenyl-1-propanol (2r)

Purified by column chromatography using petroleum ether/EtOAc = 10:1 as eluent. Obtained as a colorless oil (125.1 mg, 92%). 1H NMR (500 MHz, CDCl3) δ 7.26–7.23 (m, 2H), 7.17–7.16 (m, 3H), 3.60 (t, J = 6.5 Hz, 2H), 2.82 (s, 1H), 2.65 (t, J = 7.7 Hz, 2H), 1.87–1.81 (m, 2H). 13C{1H} NMR (125 MHz, CDCl3) δ 141.9, 128.4, 128.4, 125.8, 62.0, 34.2, 32.1. Spectroscopic data for the title compound were consistent with those reported in the literature.[3c]

Phenethyl Alcohol (2s)

Purified by column chromatography using petroleum ether/EtOAc = 10:1 as eluent. Obtained as a colorless oil (100.3 mg, 82%). 1H NMR (500 MHz, CDCl3) 7.30–7.27 (m, 2H), 7.21–7.18 (m, 3H), 3.76 (t, J = 6.5 Hz, 2H), 2.80 (t, J = 6.7 Hz, 2H), 2.35 (s, 1H). 13C{1H} NMR (125 MHz, CDCl3) δ 138.6, 129.1, 128.5, 126.4, 63.6, 39.2. Spectroscopic data for the title compound were consistent with those reported in the literature.[7]

4-Chlorophenethylalcohol (2t)

Purified by column chromatography using petroleum ether/EtOAc = 10:1 as eluent. Obtained as a colorless oil (124.8 mg, 80%). 1H NMR (500 MHz, CDCl3) 7.26 (d, J = 7.9 Hz, 2H), 7.14 (d, J = 7.9 Hz, 2H), 3.78 (t, J = 6.4 Hz, 2H), 2.79 (t, J = 6.4 Hz, 2H), 2.09 (s, 1H). 13C{1H} NMR (125 MHz, CDCl3) δ 137.2, 132.2, 130.4, 128.7, 63.4, 38.5. Spectroscopic data for the title compound were consistent with those reported in the literature.[3e]

2-(Pyridin-3-yl)ethanol (2u)

Purified by column chromatography using petroleum ether/EtOAc = 10:1 as eluent. Obtained as a colorless oil (64 mg, 52%). 1H NMR (500 MHz, CDCl3) 8.41–8.40 (m, 1H), 7.57–7.54 (m, 1H), 7.13–7.07 (m, 2H), 4.51 (s, 1H), 3.95 (t, J = 5.6 Hz, 2H), 2.96 (t, J = 5.6 Hz, 2H). 13C{1H} NMR (125 MHz, CDCl3) δ 160.4, 148.7, 136.7, 123.5, 121.5, 61.7, 39.4. Spectroscopic data for the title compound were consistent with those reported in the literature.[6b]

2-Furanmethanol (2v)

Purified by column chromatography using petroleum ether/EtOAc = 10:1 as eluent. Obtained as a yellow oil (88.2 mg, 90%). 1H NMR (500 MHz, CDCl3) 7.37 (s, 1H), 6.32–6.31 (m, 1H), 6.26 (d, J = 2.9 Hz, 1H), 4.55 (s, 2H), 2.65 (s, 1H). 13C{1H} NMR (125 MHz, CDCl3) δ 154.1, 142.6, 110.4, 107.8, 57.3. Spectroscopic data for the title compound were consistent with those reported in the literature.[3c]

2-Thiophenemethanol (2w)

Purified by column chromatography using petroleum ether/EtOAc = 10:1 as eluent. Obtained as a colorless oil (98.0 mg, 86%). 1H NMR (500 MHz, CDCl3) δ 7.27–7.26 (m, 1H), 6.98–6.97 (m, 2H), 4.78 (s, 2H), 2.44 (s, 1H). 13C{1H} NMR (125 MHz, CDCl3) δ 144.1, 127.0, 125.7, 125.6, 60.1. Spectroscopic data for the title compound were consistent with those reported in the literature.[6a]

3-Pyridinemethanol (2x)

Purified by column chromatography using petroleum ether/EtOAc = 10:1 as eluent. Obtained as a colorless oil (95.9 mg, 88%). 1H NMR (500 MHz, CDCl3) δ 8.49 (s, 1H), 8.44–8.43 (m, 1H), 7.74 (d, J = 7.7 Hz, 1H), 7.30–7.27 (m, 1H), 4.71 (s, 2H), 3.59 (s, 1H). 13C{1H} NMR (125 MHz, CDCl3) δ 148.5, 148.2, 137.0, 135.3, 123.7, 62.4. Spectroscopic data for the title compound were consistent with those reported in the literature.[2a]

4-(Hydroxymethyl)benzonitrile (2y)

Purified by column chromatography using petroleum ether/EtOAc = 10:1 as eluent. Obtained as a colorless oil (121.0 mg, 91%). 1H NMR (500 MHz, CDCl3) δ 7.62 (d, J = 7.4 Hz, 2H), 7.46 (d, J = 7.5 Hz, 2H), 4.75 (s, 2H), 2.44 (s, 1H). 13C{1H} NMR (125 MHz, CDCl3) δ 146.5, 132.4, 127.1, 119.0, 111.1, 64.2. Spectroscopic data for the title compound were consistent with those reported in the literature.[2a]

4-Nitrobenzyl Alcohol (2z)

Purified by column chromatography using petroleum ether/EtOAc = 10:1 as eluent. Obtained as a white solid (90.3 mg, 59%), mp 94–95 °C. 1H NMR (500 MHz, CDCl3) δ 8.19 (d, J = 7.9 Hz, 2H), 7.52 (d, J = 7.9 Hz, 2H,), 4.82 (s, 2H), 2.30 (s, 1H). 13C{1H} NMR (125 MHz, CDCl3) δ 148.4, 147.3, 127.1, 123.8, 64.1. Spectroscopic data for the title compound were consistent with those reported in the literature.[6a]

4-Ethynylbenzyl Alcohol (2za)

Purified by column chromatography using petroleum ether/EtOAc = 10:1 as eluent. Obtained as a colorless oil (106.9 mg, 81%). 1H NMR (500 MHz, CDCl3) δ 7.46 (d, J = 8.0 Hz, 2H), 7.27 (d, J = 7.9 Hz, 2H), 4.62 (s, 2H), 3.08 (s, 1H), 2.54 (s, 1H). 13C{1H} NMR (125 MHz, CDCl3) δ 141.7, 132.4, 126.8, 121.3, 83.6, 77.3, 64.7. Spectroscopic data for the title compound were consistent with those reported in the literature.[27b]

3-Cyclohexene-1-methanol (2zb)

Purified by column chromatography using petroleum ether/EtOAc = 10:1 as eluent. Obtained as a colorless oil (94.1 mg, 84%). 1H NMR (500 MHz, CDCl3) δ 5.69–5.64 (m, 1H), 3.55–3.49 (m, 2H), 2.12–2.05 (m, 3H), 1.82–1.72 (m, 3H), 1.63 (s, 1H), 1.31–1.23 (m, 1H). 13C{1H} NMR (125 MHz, CDCl3) δ 127.3, 126.0, 67.9, 36.4, 28.2, 25.3, 24.7. Spectroscopic data for the title compound were consistent with those reported in the literature.[9a]

4-Vinylbenzyl Alcohol (2zc)

Purified by column chromatography using petroleum ether/EtOAc = 10:1 as eluent. Obtained as a colorless oil (121.9 mg, 91%). 1H NMR (500 MHz, CDCl3) δ 7.37–7.34 (m, 2H), 7.27–7.25 (m, 2H), 6.73–6.65 (m, 1H), 5.75–5.69 (m, 1H), 5.24–5.20 (m, 1H), 4.59–4.58 (m, 2H), 2.44 (s, 1H). 13C{1H} NMR (125 MHz, CDCl3) δ 140.5, 137.0, 136.6, 127.3, 126.4, 113.9, 64.9. Spectroscopic data for the title compound were consistent with those reported in the literature.[17]

4-Aminobenzyl Alcohol (2zd)

Purified by column chromatography using petroleum ether/EtOAc = 1:1 as eluent. Obtained as a colorless oil (43.1 mg, 35%). 1H NMR (500 MHz, CDCl3) δ 7.15 (d, J = 7.6 Hz, 2H), 6.67 (d, J = 7.4 Hz, 2H), 4.54 (s, 2H), 3.67 (brs, 2H). 13C{1H} NMR (125 MHz, CDCl3) 146.1, 131.2, 128.9, 115.3, 65.3. Spectroscopic data for the title compound were consistent with those reported in the literature.[3d]

4-Amino-3-iodo-phenyl-methanol (2ze)

Purified by column chromatography using petroleum ether/EtOAc = 1:1 as eluent. Obtained as a colorless oil (77.2 mg, 31%). 1H NMR (500 MHz, CDCl3) δ 7.64 (s, 1H), 7.13 (d, J = 8.1 Hz, 1H), 6.72 (d, J = 8.1 Hz, 1H), 4.51 (s, 2H), 4.10 (brs, 2H). 13C{1H} NMR (125 MHz, CDCl3) δ 146.4, 138.2, 132.7, 128.9, 114.7, 84.1, 64.4. Spectroscopic data for the title compound were consistent with those reported in the literature.[27c]

Nonane-1,5-diol (2zf)

Purified by column chromatography using petroleum ether/EtOAc = 2:1 as eluent. Obtained as a colorless oil (124.8 mg, 78%). 1H NMR (500 MHz, CDCl3) δ 3.59–3.54 (m, 3H), 3.28 (brs, 1H), 2.93 (brs, 1H), 1.56–1.27 (m, 12H), 0.88–0.85 (m, 3H). 13C{1H} NMR (125 MHz, CDCl3) δ 71.7, 62.4, 37.3, 36.9, 32.5, 28.0, 22.8, 21.9, 14.1. Spectroscopic data for the title compound were consistent with those reported in the literature.[9b]

3-Methyl-1,4-octanediol (2zg)

Purified by column chromatography using petroleum ether/EtOAc = 2:1 as eluent. Obtained as a colorless oil (132.8 mg, 83%). 1H NMR (500 MHz, CDCl3) δ 3.72–3.52 (m, 3H), 3.37–3.34 (m, 1H), 1.73–1.63 (m, 2H), 1.54–1.22 (m, 7H), 0.91–0.85 (m, 6H). 13C{1H} NMR (125 MHz, CDCl3) δ 75.8, 75.0 (d, J = 3.3 Hz), 60.5, 60.3, 36.5, 36.1, 36.1, 35.4, 34.2, 33.3, 28.8, 28.1, 22.9, 16.6, 14.2, 14.0. Spectroscopic data for the title compound were consistent with those reported in the literature.[9b]

2-[2-(Hydroxymethyl)phenyl]ethanol (2zh)

Purified by column chromatography using petroleum ether/EtOAc = 2:1 as eluent. Obtained as a colorless oil (135.3 mg, 89%). 1H NMR (500 MHz, CDCl3) δ 7.24 (d, J = 8.0 Hz, 2H), 7.18–7.15 (m, 2H), 4.51 (s, 2H), 4.32 (brs, 1H), 3.73 (t, J = 6.0 Hz, 2H), 2.83 (t, J = 5.9 Hz, 2H), 2.40 (brs, 1H). 13C{1H} NMR (125 MHz, CDCl3) δ 139.3, 138.3, 130.2, 129.8, 128.6, 126.8, 63.3, 63.0, 35.2. Spectroscopic data for the title compound were consistent with those reported in the literature.[27d]

1,2-Benzenedimethanol (2zi)

Purified by column chromatography using petroleum ether/EtOAc = 2:1 as eluent. Obtained as a colorless oil (118.7 mg, 86%). 1H NMR (500 MHz, CDCl3) δ 7.26 (s, 4H), 4.54 (s, 4H), 4.30 (s, 2H). 13C{1H} NMR (125 MHz, CDCl3) δ 139.2, 129.5, 128.4, 63.5. Spectroscopic data for the title compound were consistent with those reported in the literature.[2b]

1-Phenylethan-1-ol (2zj)

Purified by column chromatography using petroleum ether/EtOAc = 3:1 as eluent. Obtained as a colorless oil (106.2 mg, 87%). 1H NMR (500 MHz, CDCl3) δ 7.32–7.31 (m, 4H), 7.24 (m, 1H), 4.81 (q, J = 6.3 Hz, 1H), 2.55 (s, 1H), 1.44 (d, J = 6.5 Hz, 3H). 13C{1H} NMR (125 MHz, CDCl3) δ 145.9, 128.6, 127.6, 125.5, 70.5, 25.3. Spectroscopic data for the title compound were consistent with those reported in the literature.[3a]

1-Phenoxypropan-2-ol (2zk)

Purified by column chromatography using petroleum ether/EtOAc = 3:1 as eluent. Obtained as a colorless oil (141.4 mg, 93%). 1H NMR (500 MHz, CDCl3) δ 7.31–7.28 (m, 2H), 6.99–6.96 (m, 1H), 6.92 (d, J = 7.9 Hz, 2H), 4.20 (s, 1H), 3.95 (dd, J1 = 9.2 Hz, J2 = 3.1 Hz, 1H), 3.82–3.79 (m, 1H), 2.53 (s, 1H), 1.29 (d, J = 6.4 Hz, 3H). 13C{1H} NMR (125 MHz, CDCl3) δ 158.7, 129.6, 121.2, 114.7, 73.4, 66.4, 18.9. Spectroscopic data for the title compound were consistent with those reported in the literature.[27e]

1-(o-Tolyloxy)propan-2-ol (2zl)

Purified by column chromatography using petroleum ether/EtOAc = 3:1 as eluent. Obtained as a colorless oil (144.4 mg, 87%). 1H NMR (500 MHz, CDCl3) δ 7.17–7.15 (m, 2H), 6.91–6.88 (m, 1H), 6.82 (d, J = 8.4 Hz, 1H), 4.23 (s, 1H), 3.95 (dd, J1 = 9.2 Hz, J2 = 3.1 Hz, 1H), 3.82 (t, J = 8.0 Hz, 1H), 2.40 (s, 1H), 2.26 (s, 3H), 1.31 (d, J = 6.4 Hz, 3H). 13C{1H} NMR (125 MHz, CDCl3) δ 156.7, 130.9, 127.0, 126.9, 121.0, 111.4, 73.4, 66.6, 19.0, 16.4. Spectroscopic data for the title compound were consistent with those reported in the literature.[27e]

1-(2-Methoxyphenoxy)propan-2-ol (2zm)

Purified by column chromatography using petroleum ether/EtOAc = 3:1 as eluent. Obtained as a colorless oil (152.9 mg, 84%). 1H NMR (500 MHz, CDCl3) δ 6.98–6.89 (m, 4H), 4.20–4.17 (m, 1H), 4.00 (dd, J1 = 9.6 Hz, J2 = 2.6 Hz, 1H), 3.86 (s, 3H), 3.79 (t, J = 9.0 Hz, 1H), 3.24 (s, 1H), 1.24 (d, J = 6.5 Hz, 3H). 13C{1H} NMR (125 MHz, CDCl3) δ 150.1, 148.3, 122.3, 121.2, 115.5, 112.1, 76.0, 66.1, 55.9, 18.5. Spectroscopic data for the title compound were consistent with those reported in the literature.[27e]

1-([1,1′-Biphenyl]-2-yloxy)propan-2-ol (2zn)

Purified by column chromatography using petroleum ether/EtOAc = 3:1 as eluent. Obtained as a colorless oil (212.0 mg, 93%). 1H NMR (500 MHz, CDCl3) δ 7.52 (d, J = 7.6 Hz, 2H), 7.44–7.41 (m, 2H), 7.35–7.31 (m, 3H), 7.09–7.06 (m, 1H), 6.99 (d, J = 8.1 Hz, 1H), 4.07–4.04 (m, 1H), 3.98 (dd, J1 = 9.1 Hz, J2 = 2.8 Hz, 1H), 3.75 (t, J = 8.5 Hz, 1H), 2.05 (s, 1H), 1.19 (d, J = 6.4 Hz, 3H). 13C{1H} NMR (125 MHz, CDCl3) δ 155.5, 138.5, 131.6, 131.0, 129.5, 128.8, 128.2, 127.2, 121.8, 113.5, 74.4, 66.3, 18.7. Spectroscopic data for the title compound were consistent with those reported in the literature.[27e]

2-(3-Aminophenyl)ethan-1-ol (2zo)

Purified by column chromatography using petroleum ether/EtOAc = 1:1 as eluent. Obtained as a colorless oil (72.6 mg, 53%). 1H NMR (500 MHz, CDCl3) δ 7.11–7.08 (m, 1H), 6.62 (d, J = 7.5 Hz, 1H), 6.56–6.55 (m, 2H), 3.81 (t, J = 6.5 Hz, 2H), 2.90 (brs, 2H), 2.76 (t, J = 6.5 Hz, 2H). C{1H} NMR (125 MHz, CDCl3) δ 146.6, 139.9, 129.6, 119.4, 115.9, 113.4, 63.6, 39.3. Spectroscopic data for the title compound were consistent with those reported in the literature.[24a]

2-(3-((6,7-bis(2-Methoxyethoxy)quinazolin-4-yl)amino)phenyl)ethan-1-ol (2zo-1)

Purified by column chromatography using dichloromethane/methanol = 20:1 as eluent. Obtained as a light yellow solid (392.4 mg, 95%), mp 76–77 °C. 1H NMR (500 MHz, CDCl3) δ 8.45 (s, 1H), 8.15 (brs, 1H), 7.45 (d, J = 7.9 Hz, 1H), 7.40 (s, 1H), 7.29 (s, 1H), 7.17–7.14 (m, 1H), 7.06 (s, 1H), 6.87 (d, J = 7.5 Hz, 1H), 4.11–4.08 (m, 4H), 3.77–3.72 (m, 4H), 3.66 (m, 2H), 3.36 (s, 3H), 3.32 (s, 3H), 2.74 (t, J = 5.9 Hz, 2H). 13C{1H} NMR (125 MHz, CDCl3) δ 156.8, 154.3, 153.5, 148.6. 147.1, 139.9, 138.8, 129.0, 125.0, 123.1, 120.5, 109.4, 108.2, 102.9, 70.8, 70.4, 68.8, 68.2, 63.1, 59.2, 59.2, 39.2. Spectroscopic data for the title compound were consistent with those reported in the literature.[24a]

3-(3-Trifluoromethylphenyl)propionic Acid Methyl Ester (1zp)

Purified by column chromatography using EtOAc as eluent. Obtained as a colorless oil (183.3 mg, 79%). 1H NMR (500 MHz, CDCl3) δ 7.45–7.44 (m, 2H), 7.38–7.37 (m, 2H), 3.64 (s, 3H), 2.99 (t, J = 7.7 Hz, 2H), 2.63 (t, J = 7.8 Hz, 2H). 13C{1H} NMR (125 MHz, CDCl3) δ 172.9, 141.5, 131.9, 130.8 (q, J = 32 Hz), 129.0, 125.3, 125.1 (q, J = 3.6 Hz), 123.2 (q, J = 3.7 Hz), 51.6 (d, J = 5.1 Hz), 35.3, 30.7. Spectroscopic data for the title compound were consistent with those reported in the literature.[24b]

3-(3-Trifluoromethylphenyl)propan-1-ol (2zp)

Purified by column chromatography using petroleum ether/EtOAc = 10:1 as eluent. Obtained as a colorless oil (185.6 mg, 91%). 1H NMR (500 MHz, CDCl3) δ 7.46–7.44 (m, 2H), 7.41–7.38 (m, 2H), 3.67 (t, J = 6.4 Hz, 2H), 2.76 (t, J = 7.6 Hz, 2H), 1.95 (s, 1H), 1.93–1.87 (m, 2H). 13C{1H} NMR (125 MHz, CDCl3) δ 142.9, 132.0, 130.8 (q, J = 32 Hz), 128.9, 125.5, 125.2 (q, J = 3.7 Hz), 123.3, 122.9 (q, J = 3.8 Hz), 62.0, 34.0, 31.9. Spectroscopic data for the title compound were consistent with those reported in the literature.[24b]