Mild Epoxidation of Allylic Alcohols Catalyzed by Titanium(III) Complexes: Selectivity and Mechanism.

A novel methodology for the epoxidation of a broad range of primary, secondary, and tertiary allylic alcohols is described using tert-butyl hydroperoxide as oxidant and Ti(III) species generated by reduction of Ti(IV) complexes, with manganese (0) in 1,4-dioxane under mild reaction conditions. The reaction proceeded with wide substrate scope and high chemo- and diastereoselectivity. A mechanistic pathway for the reaction is also discussed.

Introduction

The epoxidation of allylic alcohols has attracted a considerable interest in the industry since chiral epoxy alcohols are considered useful building blocks for the synthesis of biologically active molecules.[1] Currently, sharpless epoxidation is the most efficient procedure for catalytic enantioselective epoxidation of allylic alcohols.[2] 2,3-Epoxyalcohols have also been synthesized by oxidation of allylic alcohols with alkylhydroperoxids, catalyzed by d0 transition metal complexes.[3,4]

Titanocene monochloride, Cp2TiIIICl,[5] has emerged as a useful reagent in organic chemistry because of its versatility to generate single-electron-transfer reactions.[6] It is involved in a wide range of organic transformations including reduction reactions, additions to alkenes or alkynes, pinacol couplings, Barbier-type reactions and C–C bond-forming reactions.[7]

Recently, our research group has reported new mild reaction methodologies mediated by the Ti(III) species, which have allowed us the cyclopropanation of allylic alcohols,[8] transesterification of alcohols and phenols,[9] and the protection of alcohols as their 2-O-tetrahydrofuranyl and 2-O-tetrahydropyranyl ethers.[10]

Although epoxidations catalyzed by metallocenes have been reported previously,[11] the use of the Ti(III) species for epoxidation of allylic alcohols has hitherto not been reported. As a part of our program for the development of new methods mediated by metallocenes that can be applied in organic synthesis,[8−10] in this article we report the first epoxidation of allylic alcohols mediated by the Ti(III) complexes using tert-butyl hydroperoxide (TBHP) as the oxygen donor.

Results and Discussion

Our initial efforts focused on the use of geraniol (1) as a model substrate for the epoxidation. Cp2TiIIICl was prepared in situ by reduction of commercial Cp2TiCl2 (0.5 equiv) with manganese powder (12 equiv) in deoxygenated tetrahydrofuran (THF). After the solution turned to dark green (15 min),[12] a solution of 1 (1 equiv) and anhydrous TBHP (1.5 equiv) were sequentially added at room temperature (r.t.) and the mixture was stirred overnight. However, the reaction only afforded 2,3-epoxygeraniol ((±)-1a) in 8% yield and with a poor conversion (entry 1, Table and Scheme ). Furthermore, the corresponding 2-O-tetrahydrofuranyl ether was also obtained (42%).[10]

Table 1

Optimization of the Reaction Conditions

entry	Cp2TiCl2 (equiv)	Mn (equiv)	oxidant (equiv)	solvent	T	yielda
1	0.5	12.0	TBHP (1.5)	THF	r.t.	8%
2	0.5	12.0	TBHP (1.5)	1,4-dioxane	r.t.	21%
3	0.5	12.0	TBHP (4.0)	1,4-dioxane	r.t.	40%
4	0.5	12.0	TBHP (2.0)	1,4-dioxane	45 °C	43%
5	0.5	12.0	TBHP (4.0)	1,4-dioxane	45 °C	86%
6	0.5	12.0	TBHP (4.0)	THF	45 °C	3%
7	0.5	12.0	TBHP (4.0)	1,2-dimethoxyethane	45 °C	42%
8	0.5	8.0	TBHP (4.0)	1,4-dioxane	45 °C	42%
9	1.0	12.0	TBHP (4.0)	1,4-dioxane	45 °C	53%
10	0.2	8.0	TBHP (4.0)	1,4-dioxane	45 °C	61%
11	0.5	12.0	H2O2 (4.0)	1,4-dioxane	45 °C	n.r.b

Yields were evaluated by gas chromatography (GC).

n.r. = no reaction.

Scheme 1

Preliminary Experiment

Consequently, different reaction conditions and solvents were evaluated using geraniol as a model substrate, with the aim of improving the yield of the epoxidation reaction. Formation of the Ti(III) species in dry and deoxygenated 1,4-dioxane gave an enhanced yield (entry 2, Table ). Further experiments showed that the yield of (±)-1a was increased to 40% by adding 4.0 equiv of TBHP (entry 3, Table ). The yield was highly enhanced when the reaction was performed at 45 °C affording (±)-1a in 86% yield (entry 5, Table ). However, smaller amounts of TBHP (2.0 equiv) gave a lower yield (43%) under the same reaction conditions (entry 4, Table ).

Interestingly, when these latter reaction conditions were applied but THF was used as a solvent, compound (±)-1a was only isolated in 3% yield (compare entries 4 and 6, Table ) together with a 55% yield of the corresponding 2-O-tetrafuranyl ether.[10] In the light of previous reports, this change in the reactivity may be explained by any free coordination site in the catalyst being occupied by a THF molecule.[10,13] DME was a poorer solvent, generating (±)-1a in moderate yield (entry 7, Table ).

The results showed that not only was 1,4-dioxane the best solvent for this reaction but also the amounts of both Cp2TiCl2 and manganese were essential. Thus, the use of a lower equivalent of Mn(0) (entry 8, Table ) or stoichiometric and catalytic (0.2 equiv) amounts of Cp2TiCl2 (entries 9 and 10, Table ) led to a decreased yield of (±)-1a. Finally, the reaction did not occur when the oxidant was changed to H2O2 (entry 11, Table ).

With the optimized reaction conditions to hand, the roles of the reagents in the course of the reaction were evaluated (Table ). Compound (±)-1a was only obtained in 7% yield when the reaction was carried out using just TBHP (entries 1 and 2, Table ). Besides, it was noted that 2,3-epoxygeraniol ((±)-1a) was also obtained in poor yield when the epoxidation was only performed either with Cp2TiCl2 or Mn(0), suggesting that the generation of a Ti(III) species is necessary for the success of the reaction (entries 3 and 4, Table ).

Table 2

Reagent Role Evaluation in the Epoxidation Reaction of 1

entry	Cp2TiCl2 (equiv)	Mn (equiv)	TBHP (equiv)	yield (%)a
1			4.0	8
2			8.0	8
3	0.5		4.0	12
4		12	4.0	7

Yields were evaluated by GC.

The optimized epoxidation conditions were then evaluated with a series of primary, secondary, and tertiary allylic alcohols and with different substitution patterns of the alkene to define the scope of the reaction (Table ).

Table 3

Substrate Scope for the Epoxidation of Allylic Alcohols Promoted by Cp2TiIIICl

Yields were evaluated by GC.

Eight equivalent of TBHP were used.

Ratios were determined by 1H NMR.

n.r. = no reaction.

The 2,3-epoxyalcohols (±)-1a–5a, (±)-8a–b, (±)-9a–b, and (±)-12 that contained 1,1,2- and 1,2,2-trisubstituted alkenes were all obtained in excellent yields (entries 1–5, 8, 9, and 12, Table ). Furthermore, the secondary allylic alcohols were slightly more reactive than the primary alcohols and the epoxides (±)-8a–b and (±)-9a–b were obtained almost quantitatively (entries 8 and 9, Table ). However, the sterically more congested allylic alcohol 11 only gave epoxide 11a in a moderate yield (entry 11, Table ). Disubstituted alkenes were epoxidized in moderate yields (entries 6, 7, 10, and 13, Table ). A larger amount of TBHP (8 equiv) was required to increase the conversion of the primary disubstituted allylic alcohols 6 and 7 (entries 6 and 7, Table ). The reaction was also applicable to tertiary allylic alcohols. Thus, 2,3-epoxyalcohol (±)-14a was obtained in 34% yield from the tertiary monosubstituted alkene 14 (entry 14, Table ). Finally, the epoxidation did not proceed with nonallylic hydroxyl groups (entry 15, Table ) or with protected hydroxyl groups (entry 16, Table ). Thereby, a free hydroxyl group that coordinates to the titanium complex is demanded for this epoxidation.

The reaction is chemoselective for the proximal double bond (entries 1–3, 10, and 11, Table ). A remarkable feature of the reaction is its diastereoselectivity achieving the isomer with syn orientation to the hydroxyl group. Thus, the epoxide 11a obtained was enantiomerically pure from cis-carveol (11) and the epoxides (±)-12a and (±)-13a obtained were the only diastereoisomers (entries 11–13, Table ). A good erythroselectivity was observed for the A[1,2] strained substrates (±)-8 and (±)-10, typical of Ti(OiPr)4-catalyzed epoxidations (entries 8 and 10, Table ).[14] The A[1,3] strained substrate (±)-9 reacted with high threoselectivity (entry 9, Table ).

An unexpected product accompanied all of these epoxidations. Analysis of its NMR spectroscopic data led to its identification as 2-hydroxy-1,4-dioxane, which has been previously reported.[15] The formation of this oxidation product may be explained by hydrogen bonding of TBHP to the solvent facilitating a radical hydroxylation adjacent to the oxygen of the 1,4-dioxane. This has been reported in the presence of other metals such as Cu and Ni.[16] Consequently, it is necessary to use higher amounts of TBHP to obtain good yields in the presence of electron-poorer alkenes.

To obtain a deeper insight into the reaction mechanisms, the enantioselectivity of the reaction was explored with Brintzinger’s ansa-titanocene catalyst A(17) and the chiral titanium complex B(10) (Figure ), using geraniol as a model substrate. These complexes were reduced by manganese powder in dry and deoxygenated 1,4-dioxane to obtain a green solution of the corresponding Ti(III) species. Unfortunately, the reaction did not proceed with any enantioselectivity.

Figure 1

Structures of chiral titanium complexes A and B.

Nevertheless, epoxyalcohol (±)-1a was obtained in a slightly higher yield using a catalytic amount of complex B (0.1 equiv) and milder reaction conditions (r.t. and only 2.0 equiv of TBHP) (entry 1, Table ). Consequently, representative examples of allylic alcohols with different substitution patterns (3, 5, 6, (±)-8, (±)-9, 11, and 14) were subjected to these reaction conditions and to our delight, the corresponding 2,3-epoxyalcohols were also obtained in better yields compared to those in the Cp2TiIIICl reaction (entries 3, 5–8, 10, and 11, Table ). Compounds (±)-5a–6a, (±)-8a–b, and (±)-9a–b were obtained almost quantitatively. There was also a remarkable enhancement in diastereoselectivity of the reaction with the substrates (±)-8 and (±)-9 compared with epoxidation in the presence of Cp2TiIIICl (entries 7 and 8, Table ). The use of a stoichiometric amount of TBHP also led to compound (±)-9b in excellent yield (entry 9, Table ), and only traces of 2-hydroxy-1,4-dioxane were detected. However, this result could not be extended to the less reactive alkenes 1 and 3 (entries 2 and 4, Table ) probably due to their slower rate of reaction. In these cases, an extra equivalent of TBHP was required to obtain a good conversion.

Table 4

Epoxidation of Allylic Alcohols Catalyzed by B

Yields were evaluated by GC.

Ratios were determined by 1H NMR.

On the basis of the experimental results and observed chemoselectivity and diasteroselectivity, we propose the following mechanism. In the first step, Cp2TiCl2 in 1,4-dioxane is reduced by Mn(0) to Cp2TiIIICl and this complexes with the allylic alcohol to give complex C.[6b,8−10] Then, homolysis of the O–H bond affords an activated alkyloxytitanium(IV) species (D), which has been established in other reports.[7e] Reduction of D by an excess of Mn(0) would achieve E. Then, TBHP is added, which is coordinated to E, obtaining the Ti(III)–TBHP species (F). The reaction with the oxygen from TBHP produces the corresponding epoxyalcohol complex (G), with the concomitant loss of a tert-butyl alcohol (t-BuOH) molecule. Finally, the epoxyalcohol is released by coordination of a new molecule of the allylic alcohol. Thereby, complex E is again regenerated (Scheme ). It is worth noting that the characteristic green color of a Ti(III) species is retained throughout the reaction after the addition of TBHP, confirming the involvement of this species in the epoxidation reaction. Besides, the high coordination ability of allylic alcohols to form the complex E would imply that the amounts of unbounded Cp2TiIIICl are so low that the epoxide opening was not detected.[18] Finally, the formation of t-BuOH in the epoxidation was confirmed by GC–MS analysis of the reaction mixture.

Scheme 2

Proposed Mechanism for Allylic Alcohol Epoxidation

Accordingly, the epoxidation promoted by complex B could be explained following an analogous mechanism. The higher reactivity of this complex could be explained by its greater steric rigidity and lower conformational mobility.[10]

Conclusions

A new mild and highly chemoselective and diastereoselective method for the epoxidation of allylic alcohols has been developed using either bis(cyclopentadienyl)titanium chloride or the reduced form of complex B and TBHP in 1,4-dioxane. This latter complex has been shown to be a more efficient catalyst and the corresponding 2,3-epoxyalcohols were obtained in higher yields at r.t. When the reaction was performed in THF, the major reaction product was the corresponding 2-O-tetrafuranyl ether. Interestingly, 1,4-dioxane played a crucial role in the accomplishment of the reaction since it was poorly bonded to the free coordination site of the catalyst. Then, the allylic alcohol and TBHP can be coordinated to the catalyst to yield the epoxide instead of the protected alcohol.

Epoxides from electron-rich alkenes were obtained in excellent yields, whereas the epoxidation of disubstituted and monosubstituted alkenes proceeded with moderate yields. The major advantage of the reaction is its substrate scope taking place with epoxidation not only from primary and secondary allylic alcohols but also from tertiary allylic alcohols, which do not react under Sharpless epoxidation conditions, this methodology being an alternative to other widely known allylic alcohol epoxidation methods.

Experimental Section

All reactions were carried out in flame-dried flasks under argon atmosphere. The starting materials were obtained from commercial suppliers, and solvents used for column chromatography were purchased in reagent grade. THF, DME, and 1,4-dioxane were dried from Na-benzophenone and degassed for 30 min under argon before use. 1H NMR spectra were recorded on an Agilent 500 MHz spectrometer (tetramethylsilane at δH 0 ppm, CHCl3 at δH 7.25 ppm as an internal reference), and 13C NMR spectra were recorded with an Agilent 125 MHz spectrometer (CHCl3 at δC 77.00 ppm as an internal reference). Coupling constants (J) are reported in hertz (Hz). IR spectra were obtained on a Fourier transform infrared instrument. High resolution mass spectrometry (HRMS) analysis was performed on a quadrupole time-of-flight mass spectrometer using atmospheric pressure chemical ionization (APCI) in positive mode at 20 V cone voltage. GC analysis was performed using a CycloSil-B chiral column. Column chromatography was carried out on silica gel (Merck, 0.05–0.20 mesh), and thin-layer chromatography was carried out with 0.25 mm Merck silica gel plates (F254) and visualized either under UV light or by staining with vanillin solution followed by heating. High performance liquid chromatography was performed on a Hitachi/Merck L-6270 equipment using a LiChrospher Si 60 (5 μm) column.

Synthetic Procedures

Synthesis of Compound 4

Sodium borohydride (450.1 mg, 11.9 mmol) was added at r.t. to a solution of trans-2-methylbut-2-enal (1000 mg, 11.9 mmol) and CeCl3·7H2O (4433.3 mg, 11.9 mmol) in methanol (144 mL) and THF (72 mL) and stirred for further 15 min until consumption of the aldehyde. Then, it was poured with 10 mL of a solution of 1 M HCl and 50 mL of water. The solvent was evaporated in vacuo, and the aqueous phase was extracted with ethyl acetate (3 × 100 mL). The combined organic layers were washed with saturated aqueous NaCl (100 mL) and then dried over anhydrous Na2SO4. Lastly, the solvent was removed in vacuo and the residue was purified by flash chromatography using hexane/ethyl acetate (90:10) to afford trans-2-methylbut-2-enol (4) (891.7 mg, 87% yield). Physical data of 4 were consistent to those previously reported for this compound.[19]

General Procedure for the Preparation of Compounds (±)-8 and (±)-9

To a solution of the corresponding aldehydes (6 mmol) in THF (15 mL) at 0 °C was added dropwise pentylmagnesium bromide (6 mL, 2 M solution in Et2O). After 3 h at r.t., saturated NH4Cl (20 mL) was added. The layers were separated and the aqueous layer was extracted with ethyl acetate (3 × 30 mL). The organic layers were combined, washed with brine (70 mL), and then dried over Na2SO4. The corresponding alcohols, (±)-8 and (±)-9, were isolated after evaporation of the solvent by flash chromatography column on silica gel (hexane/ethyl acetate 90:10).

(±)-(E)-4-Methyldec-3-en-5-ol ((±)-8)

(841.5 mg, 82%). Colorless oil; IR (film) νmax 3357, 2960, 2932, 2872, 1668, 1459, 1378, 1259, 1016, 857 cm–1; 1H NMR (500 MHz, CDCl3) δ 5.32 (1H, t, J 7.2 Hz), 3.92 (1H, t, J 6.8 Hz), 1.99 (2H, quint, J 6.8 Hz), 1.77 (OH, s), 1.55 (3H, s), 1.51–1.44 (2H, m), 1.30–1.16 (6H, m), 0.92 (3H, t, J 7.2 Hz), 0.85 (3H, t, J 6.8 Hz); 13C NMR (125 MHz, CDCl3) δ 136.5, 128.3, 77.9, 34.7, 31.7, 25.5, 22.6, 20.7, 14.0, 13.9, 10.8; HRMS (APCI+): calcd for C11H23O [M + H]+, 171.1749; found 171.1756.

(±)-2-Methylnon-2-en-4-ol ((±)-9)

(749.7 mg, 80%). Colorless oil; IR (film) νmax 3340, 2957, 2929, 2858, 1677, 1448, 1376, 1020, 915, 843 cm–1; 1H NMR (500 MHz, CDCl3) δ 5.03 (1H, m), 4.17 (1H, q, J 6.5 Hz), 2.51 (OH, s), 1.58 (3H, s), 1.54 (3H, s), 1.46–1.40 (1H, m), 1.29–1.14 (7H, m), 0.76 (3H, t, J 7.0 Hz); 13C NMR (125 MHz, CDCl3) δ 133.6, 128.4, 68.2, 37.5, 31.7, 25.4, 24.9, 22.4, 17.8, 13.7; HRMS (APCI+): calcd for C10H21O [M + H]+, 157.1592; found 157.1599.

Preparation of Compound 11

This compound was prepared following a procedure reported in the literature. NMR data were identical to those described in the literature.[20]

Representative Procedure for Epoxidation Promoted by the Ti(III) Species

A solution of the Ti(IV) species, A or B (81.5 mg, 0.32 mmol) and Mn powder (406.9 mg, 7.68 mmol) in rigorously degassed THF, DME, or 1,4-dioxane (12.7 mL) was stirred at r.t. until a color change from red to dark green (15 min for THF and DME; 3 h for 1,4-dioxane) under inert atmosphere. Allylic alcohol (0.64 mmol) was added via syringe and stirred for further 15 min. TBHP (0.42 mL, 5.0 M solution in nonane) was added and the reaction crude was heated at 45 °C overnight. The mixture was filtered through a pad of celite after pouring water (0.5 mL). Evaporation of the solvent followed by purification of the crude product by column chromatography on silica gel gave the corresponding epoxy alcohols in the yields shown in the manuscript.

(±)-((2S*,3S*)-3-Methyl-3-(4-methylpent-3-enyl)oxiran-2-yl)methanol ((±)-1a)

NMR data of (±)-1a were identical to the previously reported data.[21]

(±)-((2S*,3R*)-3-Methyl-3-(4-methylpent-3-enyl)oxiran-2-yl)methanol ((±)-2a)

Colorless oil; IR (film) νmax 3418, 2968, 2920, 1453, 1380, 1034, 913, 865, 746 cm–1; 1H NMR (500 MHz, CDCl3) δ 5.05 (1H, m), 3.77 (1H, dd, J 12.0, 4.0 Hz), 3.59 (1H, dd, J 12.0, 7.0 Hz), 2.93 (1H, dd, J 7.0, 4.0 Hz), 2.59 (OH, s), 2.12–1.99 (2H, m), 1.64 (3H, s), 1.61 (1H, ddd, J 14.0, 10.0, 5.5 Hz), 1.57 (3H, s), 1.44 (1H, ddd, J 14.0, 10.0, 7.0 Hz), 1.30 (3H, s); 13C NMR (125 MHz, CDCl3) δ 132.3, 123.2, 64.4, 61.5, 61.1, 33.1, 25.6, 24.1, 22.1, 17.5; HRMS (APCI+): calcd for C10H19O2 [M + H]+, 171.1385; found 171.1377.

(±)-((2S*,3S*)-3-((E)-4,8-Dimethylnona-3,7-dienyl)-3-methyloxiran-2-yl)methanol ((±)-3a)

NMR data of (±)-3a agree with those previously reported data.[22]

(±)-((2S*,3S*)-2,3-Dimethyloxiran-2-yl)methanol ((±)-4a)

Colorless oil; IR (film) νmax 3420, 2977, 2930, 1460, 1380, 1030, 855 cm–1; 1H NMR (500 MHz, CDCl3) δ 4.13 (1H, q, J 6.8 Hz), 3.85 (1H, d, J 11.0 Hz), 3.49 (1H, d, J 11.0 Hz), 1.54 (3H, d, J 6.8 Hz), 1.23 (3H, s); 13C NMR (125 MHz, CDCl3) δ 74.7, 67.3, 61.3, 19.0, 18.9; HRMS (APCI+): calcd for C5H9O2 [M – H]+, 101.0603; found 101.0609.

(±)-((2S*,3S*)-2-Methyl-3-phenyloxiran-2-yl)methanol ((±)-5a)

NMR data of (±)-5a were consistent with previously reported data.[23]

(±)-((2S*,3S*)-3-Phenyloxiran-2-yl)methanol ((±)-6a)

NMR data of (±)-6a agree with those previously reported in the literature.[24]

(±)-((2S*,3S*)-3-Butyloxiran-2-yl)methanol ((±)-7a)

NMR data of (±)-7a were identical to the reported data.[25]

(S*)-1-((2S*,3S*)-3-Ethyl-2-methyloxiran-2-yl)hexan-1-ol (±)-8a

NMR data of (±)-8a agree with those previously reported in the literature.[11b]

(R*)-1-((2S*,3S*)-3-Ethyl-2-methyloxiran-2-yl)hexan-1-ol (±)-8b

NMR data of (±)-8b agree with those previously reported.[11b]

(S*)-1-((S*)-3,3-Dimethyloxiranyl)hexan-1-ol (±)-9a

Colorless oil; tR = 54 min, petroleum ether/ethyl acetate (87:13), flow = 1.0 mL/min, inseparable mixture.

(R*)-1-((S*)-3,3-Dimethyloxiran-2-yl)hexan-1-ol (±)-9b

NMR data of (±)-9b were identical to the reported data.[11b]

(S*)-3-Methyl-1-((S*)-oxiran-2-yl)but-3-en-1-ol and (S*)-3-methyl-1-((R*)-oxiran-2-yl)but-3-en-1-ol ((±)-10a) and ((±)-10b)

Colorless oil; tR = 27 min, petroleum ether/ethyl acetate (75:25), flow = 1.0 mL/min, inseparable mixture; IR (film) νmax 3425, 2956, 2923, 1453, 1371, 1224, 1050, 917, 863, 749 cm–1; 1H NMR (500 MHz, CDCl3) δ 5.02 (1H, br s), 5.01 (1H, br s), 4.84 (2H, br s), 4.34 (1H, d, J 10.0 Hz), 4.12 (1H, d, J 11.0 Hz), 2.95 (1H, d, J 4.5 Hz), 2.72 (1H, d, J 5.0 Hz), 2.68 (1H, d, J 4.5 Hz), 2.67 (OH, d, J 2.0 Hz), 2.62 (1H, d, J 5.0 Hz), 2.46 (OH, d, J 2.0 Hz), 1.98 (1H, dd, J 14.5, 2.5 Hz), 1.94 (1H, dd, J 14.5, 2.5 Hz), 1.83 (1H, dd, J 14.5, 10.0 Hz), 1.74 (6H, s), 1.64 (1H, dd, J 14.5, 10.0 Hz), 1.42 (3H, s), 1.40 (3H, s); 13C NMR (125 MHz, CDCl3) δ 147.1 (2C), 110.89, 110.88, 72.8, 72.4, 56.9, 56.3, 53.9, 53.0, 41.7, 40.4, 22.6, 21.2, 18.1, 17.9; HRMS (APCI+): calcd for C8H15O2 [M + H]+, 143.1072; found 143.1076.

(1R,2R,4S,6S)-1-Methyl-4-(prop-1-en-2-yl)-7-oxabicyclo[4.1.0]heptan-2-ol (11a)

NMR data of 11a was in agreement with the reported data.[26]

(±)-(1S*,2S*,6R*)-6-Methyl-7-oxabicyclo[4.1.0]heptan-2-ol ((±)-12a)

Colorless oil; IR (film) νmax 3428, 2953, 2917, 1465, 1372, 1034, 877, 742 cm–1; 1H NMR (500 MHz, CDCl3) δ 4.00 (1H, br s), 3.14 (1H, d, J 3.4 Hz), 2.03 (OH, d, J 9.7 Hz), 1.87–1.82 (1H, m), 1.64 (1H, m), 1.54–1.44 (3H, m), 1.34 (3H, s), 1.28–1.22 (1H, m); 13C NMR (125 MHz, CDCl3) δ 66.4, 62.2, 61.5, 29.1, 28.7, 23.7, 17.5; HRMS (APCI+): calcd for C7H13O2 [M + H]+, 129.0916; found 129.0922.

(±)-(1S*,2S*,6R*)-7-Oxabicyclo[4.1.0]heptan-2-ol ((±)-13a)

NMR data of (±)-13a matched with those previously reported in the literature.[27]

(±)-(R*)-1-(Oxiran-2-yl)cyclohexan-1-ol ((±)-14a)

Colorless oil; IR (film) νmax 3421, 2954, 2923, 1469, 1373, 1212, 1035, 877, 758 cm–1; 1H NMR (500 MHz, CDCl3) δ 3.83 (1H, br d, J 12.0 Hz), 3.69 (1H, dd, J 12.0, 7.0 Hz), 2.96 (1H, dd, J 7.0, 4.5 Hz), 1.95 (OH, s), 1.76–1.69 (2H, m) 1.60–1.49 (8H, m); 13C NMR (125 MHz, CDCl3) δ 64.0, 63.5, 61.0, 35.4, 29.5, 25.5, 24.9 (2C); HRMS (APCI+): calcd for C8H15O2 [M + H]+, 143.1072; found 143.1067.