Cp 2 TiCl 2 —Catalyzed Synthesis of Tertiary Alcohols by the Reaction of AlCl 3 with Ketones and Aryl Oleﬁns †

: We have previously obtained signiﬁcant results in the cycloalumination of oleﬁns with EtAlCl 2 in the presence of magnesium and a Cp 2 ZrCl 2 or Cp 2 TiCl 2 catalyst. Here we report the development of an efﬁcient one-pot catalytic method for the synthesis of tertiary alcohols from AlCl 3 , aryl oleﬁns, and ketones under the action of Cp 2 TiCl 2 . The developed method for producing tertiary alcohols has a general character and allows the conversion of styrene and substituted styrenes ( ortho -, para -methylstyrenes) into aryl-substituted tertiary alcohols with yields of up to 76% in the reaction with acetone or methyl ethyl ketone. We assume that the reaction proceeds through the formation of a titanacyclopropane intermediate.


Introduction
Tertiary alcohols are widely used in medicine and industry [1,2]. One of the best methods for the preparation of tertiary alcohols is the reaction of ketones with organomagnesium compounds [1,3,4]. We have previously obtained significant results in the cycloalumination of olefins with EtAlCl 2 in the presence of magnesium and a Cp 2 ZrCl 2 or Cp 2 TiCl 2 catalyst [5][6][7]. Here we report the development of an efficient one-pot catalytic method for the synthesis of tertiary alcohols from AlCl 3 , aryl olefins, and ketones under the action of Cp 2 TiCl 2 .

Results and Discussion
We found that the reaction of styrene with AlCl 3 and methyl ethyl ketone in the presence of metallic Mg as an acceptor of halide anions and Cp 2 TiCl 2 as a catalyst (10 mol%) in THF (tetrahydrofuran) solvent at 20 • C for 8 h leads to the formation of 3-methyl-1phenylpentan-3-ol 1a in a 76% yield (Scheme 1).

Introduction
Tertiary alcohols are widely used in medicine and industry [1,2]. One of the best methods for the preparation of tertiary alcohols is the reaction of ketones with organomagnesium compounds [1,3,4]. We have previously obtained significant results in the cycloalumination of olefins with EtAlCl2 in the presence of magnesium and a Cp2ZrCl2 or Cp2TiCl2 catalyst [5][6][7]. Here we report the development of an efficient one-pot catalytic method for the synthesis of tertiary alcohols from AlCl3, aryl olefins, and ketones under the action of Cp2TiCl2.

Results and Discussion
We found that the reaction of styrene with AlCl3 and methyl ethyl ketone in the presence of metallic Mg as an acceptor of halide anions and Cp2TiCl2 as a catalyst (10 mol%) in THF (tetrahydrofuran) solvent at 20 °C for 8 h leads to the formation of 3-methyl-1-phenylpentan-3-ol 1a in a 76% yield (Scheme 1). In non-ether solvents (hexane, DMSO (dimethyl sulfoxide), DMF (N,N-dimethylformamid), and methylene chloride), the yield of reaction product 1a is less than 11%. Carrying out the reaction at ~0 °C reduces its rate and the conversion of the  In non-ether solvents (hexane, DMSO (dimethyl sulfoxide), DMF (N,N-dimethylformamid), and methylene chloride), the yield of reaction product 1a is less than 11%. Carrying out the reaction at~0 • C reduces its rate and the conversion of the initial styrene, which does not exceed 20% for 15 h. With an increase in temperature to~65 • C, the reaction is completed in almost 2 h, but it is less selective. The best results were obtained when the reaction was carried out in tetrahydrofuran in the presence of Ti-containing catalysts. The reaction does not proceed in the absence of a catalyst.

Ph
The developed method for producing tertiary alcohols has a general character and allows the conversion of styrene and substituted styrenes (ortho-, para-methylstyrenes) into aryl-substituted tertiary alcohols with 66-73% yields in the reaction with acetone or methyl ethyl ketone (Scheme 2). initial styrene, which does not exceed 20% for 15 h. With an increase in temperature to ~65 °C, the reaction is completed in almost 2 h, but it is less selective. The best results were obtained when the reaction was carried out in tetrahydrofuran in the presence of Ti-containing catalysts. The reaction does not proceed in the absence of a catalyst.
The developed method for producing tertiary alcohols has a general character and allows the conversion of styrene and substituted styrenes (ortho-, para-methylstyrenes) into aryl-substituted tertiary alcohols with 66-73% yields in the reaction with acetone or methyl ethyl ketone (Scheme 2).

Scheme 2.
Cp2TiCl2-Catalyzed synthesis of tertiary alcohols by the reaction of AlCl3 with ketones and aryl olefins.

Conclusions
Thus, we have developed a new one-pot method for the production of substituted tertiary alcohols from aryl olefins and ketones in the presence of AlCl3 and catalytic amounts of Cp2TiCl2.
Experimental Procedures. A 50 mL glass reactor equipped with a magnetic stirrer under a dry argon atmosphere at 0 °C was charged under stirring with 5 mL of THF, 2 mmol aryl olefin, 4 mmol AlCl3, 2 mmol ketone, 4 mmol Mg (powder), and 0.2 mmol Cp2TiCl2. The temperature was brought to room temperature (20-21 °C) and the reaction mixture was stirred for 8 h. The reaction mixture was treated with a 7-10% HCl aqueous solution, the reaction products were extracted with diethyl ether, dried over calcined The structures of compounds 1a-d were identified using one-dimensional ( 1 H, 13 C, DEPT135) and two-dimensional (HSQC (heteronuclear single quantum correlation), HMBC (heteronuclear multiple bond correlation) and HHCOSY (HH correlation spectroscopy) NMR (nuclear magnetic resonance spectroscopy, HRMS (high resolution mass-spectrometry).

Conclusions
Thus, we have developed a new one-pot method for the production of substituted tertiary alcohols from aryl olefins and ketones in the presence of AlCl 3 and catalytic amounts of Cp 2 TiCl 2 .
Experimental Procedures. A 50 mL glass reactor equipped with a magnetic stirrer under a dry argon atmosphere at 0 • C was charged under stirring with 5 mL of THF, 2 mmol aryl olefin, 4 mmol AlCl 3 , 2 mmol ketone, 4 mmol Mg (powder), and 0.2 mmol Cp 2 TiCl 2 . The temperature was brought to room temperature (20-21 • C) and the reaction mixture was stirred for 8 h. The reaction mixture was treated with a 7-10% HCl aqueous solution, the reaction products were extracted with diethyl ether, dried over calcined MgSO 4 , and the solvent was evaporated on a rotary evaporator. The products were isolated by column chromatography (silica gel L, 180/250 µ, eluent-hexane:ethyl acetate (1:1)).