Ti-Catalyzed Reaction of β-Pinene with BF₃·THF ^†

Abstract

The reaction between β-pinene and BF₃·THF in the presence of the catalytic system Cp₂TiCl₂/Mg was carried out for the first time to obtain a 1-fluoro-substituted boraspirane, undescribed previously. The reaction proceeds stereoselectively, but is complicated by the rearrangement of the β-pinene under the Ti-catalyzed reaction conditions.

1. Introduction

The Cp₂TiCl₂-catalyzed cycloboration of α-olefins with boron halides BX₃ (X = F and Cl) or RBCl₂ (R = Alk, Ar) provides a convenient one-pot procedure for the conversion of olefinic structures into a rare class of organoboron compounds—boriranes 1–6 (Scheme 1) [1,2,3,4,5]. α,ω-Dienes can also be used as monomers to obtain 1,2-disubstituted boriranes [6].

Methylenecycloalkanes were used as monomers to expand the scope of this method to prepare three-membered cyclic organoboron compounds, which allowed one to obtain spiroboriranes. As an example, 1-Phenyl-substituted spiroboracarbocycles were formed with a yield of 70–80% after the Cp₂TiCl₂-catalyzed cycloboration of methylenecycloalkanes with PhBCl₂ [7], and when BF₃·THF was used as a boron reagent, target 1-fluoro-substituted spiroboracarbocycles were formed in a mixture with isomerization products of a starting monomer (1-methylcycloalk-1-enes) [8].

We explored the cycloboration reaction of β-pinene used as the starting material to continue these studies. Pinane terpenoids are attractive monomers in organic synthesis, which is due to their availability in nature and wide practical use as raw materials to produce organic polymers [9,10], insecticides, fragrant and medicinal substances [11,12]. The studies of new transformations of natural terpenoids to obtain known and new pharmacologically active low molecular bioregulators, therefore, are relevant and in demand.

As a part of an ongoing program in our laboratories aimed at the metall-catalyzed synthesis of new organoborane compounds we, for the first time, carried out the Ti-catalyzed reaction of β-pinene with BF₃·THF.

2. Results and Discussion

We found that the reaction between β-pinene and BF₃·THF in the presence of catalytic system Cp₂TiCl₂/Mg under the developed conditions (20 mol% Cp₂TiCl₂, 40 mol% Mg, THF, 4–6 h, 50−55 °C) gives the 1′-fluoro-substituted spiro[bicyclo [3.1.1]heptane-2,2′-borirane] 7 in an 86% yield (Scheme 2).

No signals of a double bond of the methylene group C²=C¹⁰H₂ were observed in ¹H and ¹³C NMR spectra of the reaction mixture after the reaction termination. The signal of a C⁷ bridge carbon atom was detected in a more high-frequency field (up to 33.01 ppm) of a ¹³C NMR spectrum in comparison with that of a starting β-pinene (27.8 ppm), which indicated its complete consumption. In addition, the difference in ¹H NMR chemical shifts of C⁷H^A and C⁷H^B diastereotopic protons of the reaction product 7 was 1.46 ppm, whereas it was 0.89 ppm in the starting β-pinene. The signals of carbon and hydrogen atoms of the C¹⁰H₂–B–C²(C¹H)(C³H₂)(C_q⁶) group directly bound to a quadrupole boron atom or 2–3 chemical bonds away were expectedly not detected in ¹H and ¹³C NMR time scales [13], which is typical for three-membered cyclic systems (a series of boriranes [1,2,3,4,5,6], [14] and borirenes [15,16]). The ¹¹B NMR spectrum of the compound 7 contains a broadened signal at δ_B −0.97 ppm, and ¹⁹F NMR spectrum shows a signal at δ_F −151.09 ppm. Additional signals at δ_B −0.01 and δ_F −155.78 ppm in the ¹¹B and ¹⁹F NMR spectra, respectively, are assigned to BF₃ that forms a complex with the boraspirane 7. The reaction product characterized with multinuclear NMR spectroscopy, therefore, was 1′-fluoro-substituted spiro[bicyclo[3.1.1]heptane-2,2′-borirane] 7 formed under the reaction conditions as a complex with boron trifluoride.

In the mass spectrum of the compound 7, the molecular ion peak is absent, but the oxidation product 8 yields a fragmentary ion peak with m/z 152 [M-BF]+ by loss of BF group (Scheme 3).

The fact that mirtanol 9 with its exclusively cis configuration is formed indicates that the reaction is stereoselective.

The o-ment-6-en-8-ol 10 was isolated as a byproduct in a 20% yield after the hydrolysis (Figure 1). It is known that β-pinene undergoes the skeletal rearrangements of a pinane backbone in the presence of acid catalysts (such as boron trifluoride or Ti compounds) to form monocyclic and acyclic products (derivatives of α-pinene, limonene, myrcene, etc.). It is obvious that the monocyclic o-ment-6-en-8-ol 10 is a product of double bond isomerization and C⁵–C⁶ bond cleavage of a four-membered fragment of β-pinene under the reaction conditions. We observed previously the isomerization of α-olefins to isomeric alk-2-enes [2] and methylenecycloalkanes to 1-methylcycloalk-1-enes [8] under the conditions of Ti-catalyzed cycloboration with boron trifluoride.

3. Conclusions

In summary, we performed the cycloboration of β-pinene for the first time using BF₃·THF reagent in the presence of a Cp₂TiCl₂/Mg two-component catalytic system to obtain 1′-fluoro-substituted spiro[bicyclo[3.1.1]heptane-2,2′-borirane 7, undescribed previously. Skeletal rearrangements of the bicyclic backbone of β-pinene are possible under the conditions of Ti-catalyzed reaction. The development of new methods and approaches to prepare boron-containing derivatives is of great practical interest from the point of view of creating new molecules with potential biological activity.

4. Experimental Part

All reactions with organometallic and organoboron compounds were performed using standard Schlenk techniques. β-Pinene, BF₃·THF and Cp₂TiCl₂ were obtained from commercial sources and used without further purification. THF was dried by distillation over sodium/benzophenone and stored under an argon atmosphere. The ¹H, ¹³C, ¹¹B, ¹⁹F and 2D homo- (COSY) and heteronuclear (HSQC, HMBC, DOSY) NMR spectra were measured in CDCl₃ on a Bruker Avance-400 spectrometer [400.13 (¹H), 100.62 (¹³C), 128.33 (¹¹B), 376.37 (¹⁹F) MHz]. The chemical shifts (δ) are given in parts per million (ppm) relative to Me₄Si (for ¹H and ¹³C NMR chemical shifts), BF₃·Et₂O (¹¹B NMR) and CCl₃F (¹⁹F NMR) standards. Multiplicity is given in br, s, d and m for broad, singlet, doublet and multiplet, respectively. Coupling constants (J) are given in Hz. Mass spectra were recorded on Shimadzu GCMS-QP2010 Ultra, capillary column Supelco PTE-5 (60 m × 0.25 mm, carrier gas helium, ramp from 40 to 280 °C at a rate 8 deg/min, ionizing electrons energy 70 eV, injector temperature 260 °C, ion source temperature 200 °C).

Chromatographic analysis was performed on a chromatograph using a 2000 × 2 mm column (SE-30 (5%) stationary phase on Chromaton N-AW-HMDS (0.125–0.160 mm), helium carrier gas (30 mL/min), and temperature programming from 50 to 300 °C at an 8 °C/min rate).

Cp₂TiCl₂-catalyzed reaction of β-Pinene with BF₃·THF. A glass reactor (20 mL) under a dry argon atmosphere at 0 °C was charged under stirring with Cp₂TiCl₂ (0.4 mmol, 0.10 g), magnesium (powder) (1.6 mmol, 0.04 g), THF (10 mL), β-pinene (2 mmol) and BF₃·THF (8 mmol, 1.12 g). The temperature was raised to ~50‒55 °C and the mixture was stirred about 4–6 h. Then the reaction mixture was cooled to room temperature and centrifuged, the excess of magnesium was filtered off, the solvent was evaporated, and boraspirane 7 was analyzed by NMR spectroscopy in an argon atmosphere in CDCl₃.

1′-Fluoro-spiro[bicyclo[3.1.1]heptane-2,2′-borirane] (7): Yield 86% (determined by ¹H NMR), ¹H NMR: δ 2.35–2.41 (m, 1H, CH^A), 2.00–2.05 (m, 1H, CH), 1.88–1.97 (m, 2H, CH, CH^A), 1.42–1.50 (m, 1H, CH^B), 1.21 (br s, 3H), 1.00 (br s, 3H), 0.91–0.96 (m, 1H, CH^B) ppm. ¹³C NMR: δ 42.7, 41.3, 33.0, 28.0, 23.1, 18.5 ppm. ¹¹B NMR: δ −0.97, −0.01 (BF₃) ppm. ¹⁹F NMR: δ −151.09, −155.78 (BF₃) ppm. GC-MS: m/z 152 [M−BF]⁺.

Cp₂TiCl₂-catalyzed reaction of β-Pinene with BF₃·THF after addition water. To a solution of boraspirane 7, synthesized according to above described procedures, water (2 mL) was added under oxygen atmosphere and the mixture was stirred for 1 h. The organic layer was separated, the aqueous layer was extracted with diethyl ether (2 × 10 mL), extracts were combined with the organic phase. The solvent was evaporated and the residue was distilled under reduced pressure.

cis-Myrtanol (9): Yield 63% (0.194 g), colorless oil, ${[\mathsf{\alpha }]}_{\mathrm{D}}^{21}$ = −8,6 (CHCl₃, c = 0.081), bp 85 °C (4 mm). ¹H NMR: δ 3.55–3.63 (m, 2H), 2.36–2.42 (m, 1H), 2.23–2.30 (m, 1H), 2.02–2.07 (m, 1H), 1.87–2.01 (m, 4H), 1.42–1.52 (m, 1H), 1.21 (s, 3H), 0.99 (s, 3H), 0.96 (d, J = 9.5 Hz, 1H) ppm. ¹³C NMR: δ 76.8, 44.4, 42.8, 41.4, 38.6, 33.1, 27.9, 25.9, 23.3, 18.7 ppm. GC-MS: m/z 136 (10%) [M−H₂O]⁺.

o-Menth-6-en-8-ol (10): Yield 25% (0.077 g), colorless oil, ${[\mathsf{\alpha }]}_{\mathrm{D}}^{21}$ = −78,1 (CHCl₃, c = 0.44), bp 70 °C (1 mm). ¹H NMR: δ 5.38–5.43 (m, 1H), 1.97–2.11 (m, 3H), 1.86–1.94 (m, 1H), 1.77–1.85 (m, 1H), 1.67 (s, 3H), 1.52 (m, 1H), 1.24–1.32 (m, 1H), 1.21 (s, 3H), 1.19 (s, 3H) ppm. ¹³C NMR: δ 134.0, 120.52, 72.7, 44.9, 30.9, 27.4, 26.8, 26.2, 23.9, 23.3 ppm. GC-MS: m/z 136 (4%) [M−H₂O]⁺.