Ti-Catalyzed Reaction of β -Pinene with BF 3 · THF †

: The reaction between β -pinene and BF 3 · THF in the presence of the catalytic system Cp 2 TiCl 2 /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.

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].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 Cp 2 TiCl 2 -catalyzed cycloboration of methylenecycloalkanes with PhBCl 2 [7], and when BF 3 •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 BF 3 •THF.

Results and Discussion
We found that the reaction between β-pinene and BF  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.

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]in an 86% yield (Scheme 2).No signals of a double bond of the methylene group С 2 =С 10 Н2 were observed in 1 Н and 13 С NMR spectra of the reaction mixture after the reaction termination.The signal of a C 7 bridge carbon atom was detected in a more high-frequency field (up to 33.01 ppm) of a 13 C NMR spectrum in comparison with that of a starting β-pinene (27.8 ppm), which indicated its complete consumption.In addition, the difference in 1 H NMR chemical shifts of C 7 H A and C 7 H 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 C 10 H2-B-C 2 (C 1 H)(C 3 H2)(Cq 6 ) group directly bound to a quadrupole boron atom or 2-3 chemical bonds away were expectedly not detected in 1 H and 13 C 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 11 B NMR spectrum of the compound 7 contains a broadened signal at δВ -0.97 ppm, and 19 F NMR spectrum shows a signal at δF −151.09ppm.Additional signals at δB -0.01 and δF -155.78 ppm in the 11 B and 19 F 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).No signals of a double bond of the methylene group C 2 =C 10 H 2 were observed in 1 H and 13 C NMR spectra of the reaction mixture after the reaction termination.The signal of a C 7 bridge carbon atom was detected in a more high-frequency field (up to 33.01 ppm) of a 13 C NMR spectrum in comparison with that of a starting β-pinene (27.8 ppm), which indicated its complete consumption.In addition, the difference in 1 H NMR chemical shifts of C 7 H A and C 7 H 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 ) group directly bound to a quadrupole boron atom or 2-3 chemical bonds away were expectedly not detected in 1 H and 13 C 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 11 B NMR spectrum of the compound 7 contains a broadened signal at δ B −0.97 ppm, and 19 F 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 11 B and 19 F NMR spectra, respectively, are assigned to BF 3 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).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.

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 С 2 =С 10 Н2 were observed in 1 Н and 13 С NMR spectra of the reaction mixture after the reaction termination.The signal of a C 7 bridge carbon atom was detected in a more high-frequency field (up to 33.01 ppm) of a 13 C NMR spectrum in comparison with that of a starting β-pinene (27.8 ppm), which indicated its complete consumption.In addition, the difference in 1 H NMR chemical shifts of C 7 H A and C 7 H 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 C 10 H2-B-C 2 (C 1 H)(C 3 H2)(Cq 6 ) group directly bound to a quadrupole boron atom or 2-3 chemical bonds away were expectedly not detected in 1 H and 13 C 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 11 B NMR spectrum of the compound 7 contains a broadened signal at δВ -0.97 ppm, and 19 F NMR spectrum shows a signal at δF −151.09ppm.Additional signals at δB -0.01 and δF -155.78 ppm in the 11 B and 19 F 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 C 5 -C 6 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 Ticatalyzed cycloboration with boron trifluoride.Scheme 3. Oxidation of 1-fluoro-substituted boraspirane 7 by oxygen with subsequent hydrolysis.
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 C 5 -C 6 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.

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′-borirane7, 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.

Conclusions
In summary, we performed the cycloboration of β-pinene for the first time using BF 3 •THF reagent in the presence of a Cp 2 TiCl 2 /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.

Experimental Part
All reactions with organometallic and organoboron compounds were performed using standard Schlenk techniques.β-Pinene, BF 3 •THF and Cp 2 TiCl 2 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 1 H, 13 C, 11  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).