HYDROSILANE/LEWIS ACID ADDUCT, PARTICULARLY ALUMINUM, IRON, AND ZINC, METHOD FOR PREPARING SAME, AND USE OF SAID SAME IN REACTIONS FOR REDUCING CARBONYL DERIVATIVES

Abstract

Disclosed is an adduct between a Lewis acid, preferably aluminum trichloride, iron trichloride, or zinc dichloride, and a hydrosilane;—a method for preparing same; and a method for for reducing, particularly, an aldehyde, a ketone, an α,β-unsaturated ketone, an imine, or an α,β-unsaturated imine.

Claims

1. A pre-formed adduct between a Lewis acid selected from the salts of zinc (II), tin (II) or (IV), iron (II) or iron (III), copper (I), palladium (II), titanium (III) or (IV), bismuth (III) or aluminium (III) and a hydrosilane.

2. An adduct according to claim 1, wherein the Lewis acid is a salt of zinc (II), especially zinc dichloride, a salt of iron (III), especially iron trichloride, or a salt of aluminium (III), especially aluminium trichloride.

3. An adduct according to claim 1, wherein the hydrosilane is selected from the trialkylsilanes, such as triethylsilane (Et.sub.3SiH) and tri(isopropyl)silane, tris(trimethylsilyl)silane, triphenylsilane, the polymethylhydrosiloxanes (PMHS), the polydimethylsiloxanes having a terminal Si—H group, such as tetramethyldisiloxane, the methylhydro-dimethylsiloxane copolymer, the methylhydrophenyl-methylsiloxane copolymer, the methylhydrocyanopropylsiloxane copolymer, the methylhydromethyloctylsiloxane copolymer, poly(1,2-dimethylhydrosilazane), the 1-methyl-hydrosilazane) (1,2-dimethylhydrosilazane) copolymer, and methylhydrocyclosiloxane.

4. An adduct according to claim 3, wherein the hydrosilane is selected from polymethylhydrosiloxane, tetramethyldisiloxane and triethylsilane.

5. An adduct according to claim 1, further comprising another Lewis acid, a metal salt, an alcohol, or a dihalogen.

6. An adduct according to claim 5, comprising an alcohol, advantageously iso-propanol or tert-butanol, especially in a molar ratio of Lewis acid/alcohol of 1:2.

7. An adduct AlCl.sub.3/triethylsilane/isopropanol in a molar ratio of 0.3:1:0.6.

8. An adduct FeCl.sub.3/triethylsilane/iso-propanol or FeCl.sub.3/triethylsilane/tert-butanol in a molar ratio of x:1:2x, where X varies from 0.01 to 1, advantageously from 0.05 to 0.3 and is preferably 0.05.

9. A method for performing a reaction of reduction of an aldehyde, an α,β-unsaturated aldehyde, a ketone, an α,β-unsaturated ketone, an imine, or an α,β-unsaturated imine, comprising providing the adduct of claim 1, and combining the adduct with the aldehyde, α,β-unsaturated aldehyde, ketone, α,β-unsaturated ketone, imine, or α,β-unsaturated imine.

10. The method according to claim 9, wherein the reduction is of a ketone or an α,β-unsaturated ketone, especially a compound comprising a cyclopentanone or cyclopentenone motif, such as jasmone and dihydrojasmone; cyclohexanone or cyclohexenone, such as pulegone or menthone; or an aryl-vinyl ketone motif, such as frambinone.

11. The method according to claim 10, wherein the reduction is of a ketone, an α,β-unsaturated ketone, an imine, or an α,β-unsaturated imine of formula (Ia): ##STR00035## in which: X is O or N R.sub.a, R.sub.a being selected from linear or branched alkyl having at most 12 carbon atoms, linear or branched alkylene having at most 6 carbon atoms, carbocyclic or heterocyclic aryl, an aralkyl radical, each of these alkyl, alkylene, aralkyl or aryl radicals being optionally substituted, is a single bond or a double bond, R.sub.1 is a linear or branched alkyl radical having at most 12 carbon atoms, linear or branched alkylene having at most 12 carbon atoms, a saturated or unsaturated cycloalkyl radical having 3 to 7 carbon atoms and optionally comprising one or more heteroatoms selected from nitrogen, sulfur or oxygen atoms, a carbocyclic or heterocyclic aryl radical, an aralkyl radical, each of these alkyl, alkylene, aralkyl or aryl radicals being optionally substituted, R.sub.2 is hydrogen, linear or branched alkyl having at most 12 carbon atoms, linear or branched alkylene having at most 6 carbon atoms, carbocyclic or heterocyclic aryl, an aralkyl radical, each of these alkyl, alkylene, aralkyl or aryl radicals being optionally substituted, R.sub.3 and R.sub.4, which are identical or different, are hydrogen, linear or branched alkyl having at most 12 carbon atoms, linear or branched alkylene having at most 6 carbon atoms, carbocyclic or heterocyclic aryl, an aralkyl radical, each of these alkyl, alkylene, aralkyl or aryl radicals being optionally substituted, and when is a single bond, R.sub.5 is hydrogen, linear or branched alkyl having at most 12 carbon atoms, linear or branched alkylene having at most 12 carbon atoms, carbocyclic or heterocyclic aryl, an aralkyl radical, each of these alkyl, alkylene, aralkyl or aryl radicals being optionally substituted, and R.sub.6 is hydrogen, linear or branched alkyl having at most 12 carbon atoms, linear or branched alkylene having at most 12 carbon atoms, carbocyclic or heterocyclic aryl, an aralkyl radical, each of these alkyl, alkylene, aralkyl or aryl radicals being optionally substituted, or a cyclic ketone, α,β-unsaturated ketone, imine or α,β-unsaturated imine of formula (Ib): ##STR00036## in which: n=0 or 1, X and are as defined above, R.sub.7 is a linear or branched alkyl radical having at most 12 carbon atoms, linear or branched alkylene having at most 12 carbon atoms, a saturated or unsaturated cycloalkyl radical having 3 to 7 carbon atoms and optionally comprising one or more heteroatoms selected from nitrogen, sulfur or oxygen atoms, a carbocyclic or heterocyclic aryl radical, an aralkyl radical, each of these alkyl, alkylene, aralkyl, aryl or cycloalkyl radicals being optionally substituted, advantageously an alkyl radical having at most 12 carbon atoms, R.sub.9 is a hydrogen, a linear or branched alkyl radical having at most 12 carbon atoms, linear or branched alkylene having at most 12 carbon atoms, a saturated or unsaturated cycloalkyl radical having from 3 to 7 carbon atoms and optionally comprising one or more heteroatoms selected from nitrogen, sulfur or oxygen atoms, a carbocyclic or heterocyclic aryl radical, an aralkyl radical, each of these alkyl, alkylene, aralkyl or aryl radicals being optionally substituted, or a CHR.sub.12—COOR.sub.13 group, in which R.sub.12 is hydrogen, a linear or branched alkyl radical having at most 12 carbon atoms, and R.sub.13 is a linear or branched alkyl radical having at most 12 carbon atoms, a saturated or unsaturated cycloalkyl radical having from 3 to carbon atoms and optionally comprising one or more heteroatoms selected from nitrogen, sulfur or oxygen atoms, a carbocyclic aryl radical, an aralkyl radical, each of these alkyl, alkylene, aralkyl or aryl radicals being optionally substituted, and when is a single bond, R.sub.8, and R.sub.10, which are identical or different, are a hydrogen, a linear or branched alkyl radical having at most 12 carbon atoms, linear or branched alkylene having at most 12 carbon atoms, a saturated or unsaturated cycloalkyl radical having from 3 to 7 carbon atoms and optionally comprising one or more heteroatoms selected from nitrogen, sulfur or oxygen atoms, a carbocyclic or heterocyclic aryl radical, an aralkyl radical, each of these alkyl, alkylene, aralkyl or aryl radicals being optionally substituted, or a CHR.sub.12—COOR.sub.13 group, in which R.sub.12 is hydrogen, a linear or branched alkyl radical having at most 12 carbon atoms, and R.sub.13 is a linear or branched alkyl radical having at most 12 carbon atoms, a saturated or unsaturated cycloalkyl radical having from 3 to carbon atoms and optionally comprising one or more heteroatoms selected from nitrogen, sulfur or oxygen atoms, a carbocyclic aryl radical, R.sub.11 is hydrogen, a linear or branched alkyl radical having at most 12 carbon atoms, linear or branched alkylene having at most 12 carbon atoms, a saturated or unsaturated cycloalkyl radical having from 3 to 7 carbon atoms and optionally comprising one or more heteroatoms selected from nitrogen, sulfur or oxygen atoms, a carbocyclic or heterocyclic aryl radical, an aralkyl radical, each of these alkyl, alkylene, aralkyl or aryl radicals being optionally substituted, advantageously an alkyl radical having at most 12 carbon atoms, or, when is a single bond, R.sub.7 and R.sub.8 are together a ═CH—R.sub.7a group where R.sub.7a is hydrogen, a linear or branched alkyl radical having at most 11 carbon atoms, a saturated or unsaturated cycloalkyl radical having from 3 to 7 carbon atoms and optionally comprising one or more heteroatoms selected from nitrogen, sulfur or oxygen atoms, a carbocyclic or heterocyclic aryl radical, an aralkyl radical, each of these alkyl, alkylene, aralkyl or aryl radicals being optionally substituted, advantageously an alkyl radical having at most 11 carbon atoms, or for the reduction of a compound of the following formula (IV): ##STR00037## in which R.sub.18 and R.sub.19 are, independently of one another, an optionally substituted linear or branched alkyl radical having at most 11 carbon atoms, R.sub.18 and R.sub.19 are linked together to form a saturated or unsaturated cycloalkyl radical having from 3 to 7 carbon atoms and optionally comprising one or more heteroatoms selected from nitrogen, sulfur or oxygen atoms.

12. A method for preparing a compound of formula (IIIb): ##STR00038## in which: R.sub.15 and R.sub.16 are, independently of one another, hydrogen, an optionally substituted linear or branched alkyl radical having at most 12 carbon atoms, advantageously selected from methyl, ethyl, propyl, advantageously isopropyl, and butyl, advantageously tert-butyl, an optionally substituted linear or branched alkylene radical having at most 12 carbon atoms, an optionally substituted linear or branched alkoxy radical having at most 12 carbon atoms, advantageously selected from methoxy, ethoxy, propoxy, advantageously isopropoxy, and butoxy, advantageously tert-butoxy, OH, COOR.sub.13 where R.sub.13 is as a linear or branched alkyl radical having at most 12 carbon atoms, a saturated or unsaturated cycloalkyl radical having from 3 to 7 carbon atoms, CF.sub.3, halogen selected from F, Cl, Br and I, said substituents R.sub.15 and R.sub.16 being positioned in the ortho, meta or para position of the ring, advantageously in the meta and para positions, R.sub.15 and R.sub.16 advantageously being selected from an optionally substituted linear or branched alkoxy radical having at most 12 carbon atoms, especially methoxy, ethoxy, propoxy, advantageously isopropoxy, and butoxy, advantageously tert-butoxy, and OH, R.sub.17 is a linear or branched alkyl radical having at most 12 carbon atoms, advantageously an alkyl group selected from methyl, ethyl, propyl, advantageously isopropyl, and butyl, advantageously tert-butyl, especially methyl, comprising a step of contacting a compound of formula (IIa) ##STR00039## with an adduct according to claim 1.

13. A method according to claim 12, in which the compound of the following formula (IIIa1): ##STR00040## in which R.sub.15 and R.sub.16, independently of one another, are an optionally substituted linear or branched alkoxy radical having at most 12 carbon atoms, especially methoxy, ethoxy, propoxy, advantageously isopropoxy, and butoxy, advantageously tert-butoxy, or OH, R.sub.17 is a linear or branched alkyl radical having at most 12 carbon atoms, advantageously selected from methyl, ethyl, propyl, advantageously isopropyl, and butyl, advantageously tert-butyl, especially methyl. comprising a step of contacting a compound of formula (IIa1) ##STR00041## with an adduct according to claim 1.

14. A method for preparing a compound of the following compound (IIIb): ##STR00042## in which: is a single bond or a double bond, R.sub.14 is hydrogen, a linear or branched alkyl radical having at most 11 carbon atoms, a linear or branched alkylene having at most 11 carbon atoms, especially a linear alkyl radical having at most 11 carbon atoms or a COOR.sub.13 group where R.sub.13 is a linear or branched alkyl radical having at most 12 carbon atoms, a saturated or unsaturated cycloalkyl radical having from 3 to 7 carbon atoms, advantageously in which R.sub.13 is a linear or branched alkyl radical having at most 12 carbon atoms, especially a methyl, ethyl, propyl, advantageously isopropyl, and butyl, advantageously tert-butyl, radical comprising a step of contacting a compound of formula (IIb) ##STR00043## with an adduct according to any claim 1.

15. A method for preparing a dialkylether of the following formula (V): ##STR00044## in which R.sub.18 and R.sub.19 are, independently of one another, an optionally substituted linear or branched alkyl radical having at most 11 carbon atoms, or R.sub.18 and R.sub.19 are linked together to form a saturated or unsaturated cycloalkyl radical having from 3 to 7 carbon atoms and optionally comprising one or more heteroatoms selected from nitrogen, sulfur or oxygen atoms, comprising a step of contacting a compound of the following formula (IV): ##STR00045## with an adduct according to claim 1.

16. A method for preparing a dicycloalkylether of the following formula (Va): ##STR00046## in which n=1 to 4, advantageously 2 or 3, and optionally comprising one or more heteroatoms selected from nitrogen, sulfur or oxygen atoms, comprising a step of contacting a cyclic ketone of the following formula (IVa): ##STR00047## with an adduct according to claim 1.

17. An adduct according to claim 2, wherein the hydrosilane is selected from the trialkylsilanes, such as triethylsilane (Et3SiH) and tri(isopropyl)silane, tris(trimethylsilyl)silane, triphenylsilane, the polymethylhydrosiloxanes (PMHS), the polydimethylsiloxanes having a terminal Si—H group, such as tetramethyldisiloxane, the methylhydro-dimethylsiloxane copolymer, the methylhydrophenyl-methylsiloxane copolymer, the methylhydrocyanopropylsiloxane copolymer, the methylhydromethyloctylsiloxane copolymer, poly(1,2-dimethylhydrosilazane), the 1-methyl-hydrosilazane) (1,2-dimethylhydrosilazane) copolymer, and methylhydrocyclosiloxane.

18. An adduct according to claim 2, further comprising another Lewis acid, a metal salt, an alcohol, or a dihalogen.

19. An adduct according to claim 3, further comprising another Lewis acid, a metal salt, an alcohol, or a dihalogen.

20. An adduct according to claim 4, further comprising another Lewis acid, a metal salt, an alcohol, or a dihalogen.

Description

DESCRIPTION OF THE DRAWINGS

[0167] FIG. 1 shows the infrared spectrum of an adduct between aluminium trichloride and tetramethyldisilane (top curve) in comparison with that of methyl-THF (bottom curve) and of tetramethyldisilane (middle curve). In the spectrum of the adduct, the intensity of the peaks of the tetramethyldisilane is reduced and some peaks have appeared in different locations, indicating the presence of a new species in the adduct between aluminium trichloride and tetramethyldisilane

EXAMPLES

Example 1

Preparation of the Adduct PMHS-AlCl.SUB.3

[0168] 133 mg (1 mmol) of anhydrous AlCl.sub.3, then 500 μL of Me-THF are introduced into a flask equipped with a magnetic stirrer. The mixture is stirred at 25° C. for 10 minutes. Moderate heating is observed due to the dissolution of AlCl.sub.3 in the Me-THF. A clear pale pink to red solution is obtained. 300 μL (volume equivalent to 5 mmol hydride) of PMHS are then introduced under stirring at 25° C. A cloudy solution is obtained, this being formed of two immiscible phases. Heating to 70° C. for 30 minutes causes the solution to clear, which then becomes colourless, clear and perfectly homogeneous. The adduct PMHS-AlCl.sub.3 is ready to use in this form. It is stored in a closed container with no need for an inert atmosphere.

[0169] Other hydrosilanes can be used instead of PMHS.

[0170] For example, tetramethyldisiloxane (TMDS) was also used to prepare an adduct TMDS-AlCl.sub.3 which is just as reactive as the adduct PMHS-AlCl.sub.3 without the need for an excess of hydrosiloxane during the preparation of said adduct.

Example 2

Preparation of the Adducts

Example 2.1

Preparation of the Adduct Triethylsilane-AlCl.SUB.3

[0171] 133 mg (1 mmol) of anhydrous AlCl.sub.3 are added to 250 ml of Me-THF. Once the AlCl.sub.3 has dissolved, 800 μl (5 mmol) of triethylsilane are added. A cloudy solution is obtained having two immiscible phases. After 2 hours of heating to 80° C., a clear and homogeneous solution is obtained. The adduct Et.sub.3SiH-AlCl.sub.3 is then ready to use. Its concentration of Al is 1.086 mol/L.

Example 2.2

Preparation of the Adduct Triethylsilane-AlCl.SUB.3.-iPrOH

[0172] ##STR00025##

TABLE-US-00001 Mass n Vol. Total vol. Product M d (g) (mmol) (mL) (mL) AlCl.sub.3 133.34 — 1.000 7.5 — — 2-MeTHF 86.13 0.860 5.375 62.4 6.250 6.250 Et.sub.3SiH 116.28 0.728 2.912 25.0 4.000 10.250 i-PrOH 60.10 0.785 0.902 15.0 1.149 11.399

[0173] The 2-MeTHF is introduced into a 25 mL ground neck flask, equipped with a magnetic stirrer and internal thermometer. The 2-MeTHF is cooled to 0° C. by means of an ice bath, with stirring at 800 rpm (stirring maintained for the entire period of preparation of the adduct).

[0174] At 0° C., AlCl.sub.3 is added in 10 portions at a rate of one portion every 3 minutes. After each addition, an increase in temperature of 5 to 8° C. is observed. When the temperature of the reaction mixture has returned to 0° C., a new addition can be performed. A clear pale yellow solution is obtained. Once the 10 additions have been performed, the temperature of the reaction medium is left to return to 25° C.

[0175] Et.sub.3SiH is then added all at once with the aid of a syringe. The temperature remains stable at 25° C. The mixture obtained is stirred for 10 minutes at 25° C. The i-PrOH is then added all at once with the aid of a syringe. The temperature remains stable at 25° C. The mixture obtained is stirred for 30 minutes at 25° C. The mixture loses its colour progressively until it becomes very pale yellow. The clear solution of the adduct Et.sub.3SiH/AlCl.sub.3/i-PrOH (1:0.3:0.6) thus obtained is stored under argon at 25° C. and can be used in this form. The adduct can be stored for a number of months with no variation in its reactivity.

Example 3

Reduction of Methyl Jasmonate by the Adduct PMHS-AlCl.SUB.3

[0176] ##STR00026## [0177] 1 h, 25° C. [0178] Conversion:95% [0179] Selectivity:93%

[0180] 11.2 μL (0.05 mmol) of methyl jasmonate, 54 μL of adduct PMHS-AlCl.sub.3 (prepared with 5 hydride equivalents produced from the PMHS) (54 μL correspond to 0.06 mmol of Al and 0.3 mmol of H.sup.−) are introduced into a flask equipped with a magnetic stirrer. The solution obtained is stirred at 25° C. for 1 h. 500 μL of an HCL.sub.eq 1 M solution are then introduced. The solution is stirred at 25° C. for 5 minutes, then extracted with ethyl ether. An analysis of the ethereal extract by GC/MS indicates a conversion of 95% of the initial cyclopentanone with a selectivity of 93% for the product resulting from the reduction of the C═O into CH—OH.

Example 4

Reduction of 4-14-hydroxyphenyl)but-3-en-2-one

[0181] ##STR00027##

[0182] 8.11 mg (0.05 mmol) of 4-(4-hydroxyphenyl)but-3-en-2-one, then 200 μL of Me-THF are introduced into a flask equipped with a magnetic stirrer. A clear yellow solution is obtained. 32.4 μL of the adduct PMHS-AlCl.sub.3 (prepared with 1 hydride equivalent produced from the PMHS) (32.4 μL correspond to 0.05 mmol of Al and 0.05 mmol of H.sup.−) are then added to this solution. The solution obtained is stirred at 70° C. for 3 h. 500 μL of a solution HCl.sub.eq 1 M are then introduced. The solution is stirred for 5 minutes at 25° C., then extracted with ethyl ether. An analysis of the ethereal extract by GC/MS indicates a conversion of 94% of the initial enone and a selectivity of 73% for the 1,4 reduction product. The other products observed are 1,2 reduction products or double 1,4 and 1,2 reduction products or complete reduction products of the side chain into butyl radical.

[0183] The reduction of the 4-(4-hydroxyphenyl)but-3-en-2-one into frambinone was evaluated by comparing an adduct produced with aluminium trichloride and PMHS, an adduct produced with aluminium trichloride, and a mixture of aluminium trichloride and PMHS which were not pre-combined in the form of an adduct. The results obtained after 3 hours at 70° C. in 2-methyltetrahydrofuran are shown in table 1:

TABLE-US-00002 TABLE 1 Adduct Adduct PMHS- TMDS- PMHS and AlCl.sub.3 AlCl.sub.3 AlCl.sub.3 not pre-combined Conversion 94% 99% 99% Selectivity 73% 85% 1%

[0184] Thus, these results show that the use of a mixture of PMHS and aluminium trichloride leads to the formation of a complex mixture of products and that no selectivity for the ketone is observed.

[0185] The use of an adduct between aluminium trichloride and a hydrosilane leads to the formation of the saturated ketone with a very high yield and selectivity.

[0186] The adduct according to the present invention is thus especially effective for the selective reduction of ketones and α,β-unsaturated ketones, moreover selectively.

[0187] In addition to being very effective in terms of yield and selectivity, the PMHS-AlCl.sub.3 adduct has also proven to be more suitable for handling in relaxed conditions, since it is stable in the presence of air and does not hydrolyse spontaneously, in contrast to AlCl.sub.3, which has to be handled with care, under a hood, in a glovebox, is deliquescent and reacts violently with water.

Example 5

Reduction of 4-(4-hydroxyphenyl)but-3-en-2-one in the Presence of an Iodised Derivative

[0188] The reduction of 4-(4-hydroxyphenyl)but-3-en-2-one was also repeated in the conditions of example 3 with a triethylsilane/ammonium trichloride adduct in the presence of an iodised derivative (either CuI or iodine I.sub.2) or in the presence of an alcohol (iso-propanol).

[0189] The results are shown in table 2:

TABLE-US-00003 TABLE 2 Adduct Adduct Adduct Adduct Et.sub.3SiH—AlCl.sub.3 Et.sub.3SiH—AlCl.sub.3—Cul Et.sub.3SiH—AlCl.sub.3—I.sub.2 Et.sub.3SiH—AlCl.sub.3—iPrOH Period (1:0.3) (1:0.3:1.2) (1:0.3:1.2) (1:0.3:0.9) Conversion 1 h 86% >98% 2 h 92% 3 h 98% 91% Selectivity 1 h 97% >96% 2 h 91% 3 h 92% 100%

[0190] The adduct between aluminium trichloride and triethylsilane makes it possible to obtain the saturated ketone with an increased selectivity.

[0191] The selectivity of the 1,4 reduction can be further increased if the adduct Et.sub.3SiH/AlCl.sub.3 is used in the presence of cuprous iodide, iodine, or iso-propanol.

[0192] The use of the adduct according to the present invention in the presence of an iodised derivative or an alcohol such as iso-propanol makes it possible to completely control the reduction of an α,β-unsaturated ketone in position β.

[0193] The same reaction can be performed with an adduct between iron trichloride and a hydrosilane, especially triethylsilane. The results with iron trichloride and aluminium trichloride are summarised in table 3:

TABLE-US-00004 TABLE 3 Entry Adduct t (h) Conv. (%) Select. (%) 1 TES-AlCl.sub.3—i-PrOH 2 h 98 96 (1:0.3:0.6) 2 TES-FeCl.sub.3 (1:1) 3 h 100 78 3 TES-FeCl.sub.3 (1:0,.) 3 h 96 88 4 TES-FeCl.sub.3—i-PrOH 2 h 90 94 (1:0.3:0.6) 5 TES-FeCl.sub.3 not preformed 2 h <90 <78 (1:1)

[0194] The reaction can be carried out on a large scale (10 g) with a similar conversion and selectivity (98% conversion and 99% selectivity).

[0195] These reaction conditions can be used with the compounds of formula IIa1a, especially selected from those in which R.sub.15 is methoxy, R.sub.16 is OH and R.sub.17 is methyl; R.sub.15 is ethoxy, R.sub.16 is OH and R.sub.17 is methyl; R.sub.15 is n-propoxy, R.sub.16 is OH and R.sub.17 is methyl; R.sub.15 is i-propoxy, R.sub.16 is OH and R.sub.17 is methyl; R.sub.15 is n-butoxy, R.sub.16 is OH and R.sub.17 is methyl; R.sub.15 is i-butoxy, R.sub.16 is OH and R.sub.17 is methyl; and R.sub.15 is t-butoxy, R.sub.16 is OH and R.sub.17 is methyl.

[0196] Additional tests aimed at improving the reaction conditions and/or the reactivity with the adduct of FeCl.sub.3 were also performed.

Example 5.1

Modification of the Solvent

[0197] The reduction of the 4-(4-hydroxyphenyl)but-3-en-2-one is repeated with the adduct TES-FeCl3-i-PrOH (1:0.3:0.6). The results are compiled in table 4.

TABLE-US-00005 TABLE 4 Entry Solvent Time Temperature Conv. (%) Select. (%) 1 MeTHF 4 h 50° C. 34 100 2 MeTHF 2 h 80° C. 96 82 3 AcOEt 4 h TA 66 98 4 AcOEt 4 h 30° C. 91 78 5 AcOEt 2 h 50° C. 94 82

[0198] The choice of ethyl acetate as solvent promotes the selective reduction of 4-(4-hydroxyphenyl)but-3-en-2-one.

Example 5.2

Reduction of the Iron Catalytic Burden

[0199] Additional tests aimed at reducing the amount of FeCl.sub.3 were performed.

TABLE-US-00006 Entry FeCl.sub.3 Sol%%vent Temperature Conv. (%) Select. (%) 1 20% Me-THF 70° C. 99 92 2 10% Me-THF 70° C. 83 95 3 5% Me-THF 70° C. 16 100 4 20% AcOEt 70° C. 94 83 5 10% AcOEt 50° C. 96 80 6 10% AcOEt 70° C. 97 77 7 5% AcOEt 50° C. 55 99 8 5% AcOEt 70° C. 90 88

[0200] The amount of iron can be reduced to 5% relative to the amount of substrate whilst maintaining a high conversion and selectivity.

Example 5.3

Post-Reaction Treatment

[0201] The conditions for isolating the crude reaction product have also been the topic of studies. The isolation of the product is made difficult by the presence of silylated residues and the nature of the product (phenol).

TABLE-US-00007 HCl 1M Loss of product (too acidic) MeOH/NaOH 2M Loss of product (too alkaline) MeOH/NaOH 1M, 0.5M or 0.1M Hydrolysis by-products MeOH/K.sub.2CO.sub.3 Loss of product (too alkaline) MeOH/KOH 4M Loss of product (too alkaline) NH.sub.4OH 10% mol Hydrolysis by-products MeOH/H.sub.2O/NaF Hydrolysis by-products MeOH/NaF Hydrolysis by-products MeOH/NaHCO.sub.3 sat. Clean, no loss of product

[0202] The selected treatment conditions are thus a weakly alkaline solution during hydrolysis. The standard procedure for 0.4 mmol of hydrosilane used is as follows: MeOH (1 ml) added to the base (example: NaHCO.sub.3) (10 ml) is added to the reaction mixture. The resulting mixture is stirred at ambient temperature for 3 h, then extracted with dichloromethane Ch.sub.2Cl.sub.2 (3×20 ml). The organic phases are collected then dried over MgSO.sub.4 and the solvent is removed under reduced pressure. The crude product is filtered over silica or dicalite.

Example 6

Preparation of an Ether from Cyclohexanone

[0203] ##STR00028##

[0204] 3.9 mg (4 mmol) of cyclohexanone are added to the adduct triethylsilane-AlCl.sub.3 of example 2 and the solution is stirred at ambient temperature for 3 hours. At the end of the reaction, dicyclohexyl ether is obtained with a selectivity of 100%.

Example 7

Preparation of Cyclopentyl Methyl Ether

[0205] ##STR00029##

[0206] Cyclopentanone (0.1 mmol; 8.9 mL) is diluted in an equivalent of methanol and 40 μL of Me-THF. [TES-AlCl.sub.3] (1:1; (1 equivalent) prepared in Me-THF is added in 2 stages to the cyclopentanone. After 2 hours at 80° C., a total conversion of the cyclopentanone was obtained. 56% of CPME are obtained.

Example 8

Reduction of Pulegone

[0207] It is possible to selectively reduce the 1,4 position with the aid of the system [TES-AlCl.sub.3]. The addition of CuI, of I.sub.2, or of iso-propanol, or of zinc dichloride to the adduct [TES-AlCl.sub.3-iPrOH], or of tert-butanol makes it possible to increase the selectivity in favour of position 4. The selectivity is total with the adducts [TES-AlCl.sub.3-iPrOH+ZnCl.sub.2] and above all [TES-AlCl.sub.3-tBuOH].

[0208] It is preferable to carry out the reaction without addition of solvent other than that which is already present in the adduct.

[0209] It is also possible to chain the reduction of the1,4 then 1,2 positions so as to obtain menthol. This further reduction then requires the use of the adduct [TES-AlCl.sub.3] in excess (3 equivalents).

##STR00030##

Example 9

Reduction of Pulegone into Menthone

[0210] ##STR00031##

[0211] 8.2 μL (0.05 mmol) of pulegone are added to the adduct [TES-AlCl.sub.3-tBuOH] (molar ratio 1:0.3:0.6) or [TES-AlCl.sub.3-iPrOH-ZnCl.sub.2] (molar ratio 1:0.3:0.6:1) prepared in methyl-THF, and the solution is stirred at 80° C. for 3 hours. At the end of the reaction, the menthone is obtained with a selectivity of 92% and a yield of 73%. No trace of ether is observed.

[0212] With the adduct PMHS/FeCl.sub.3/iPrOH (3:0.3:0.6), menthone is obtained with a yield of 83% and a selectivity of 67%.

[0213] The results of the reduction of pulegone with iron trichloride and aluminium trichloride are summarised in table 5:

TABLE-US-00008 TABLEAU 5 Conv. Select. Entry Adduct t (h) Product (%) (%) 1 PMHS-AlCl.sub.3 (1:1) 2 h menthone 78 72 3 PMHS-AlCl.sub.3—i- 2 h, 90° C. menthol 100 70 PrOH (3:0.3:0.6) 4 TES-AlCl.sub.3—i-PrOH 4 h menthone 96 90 (3:0.3:0.6) 5 1) TES-AlCl.sub.3—i- 2 h menthone 100 90 PrOH (3:0.3:0.6) 2) TES-FeCl.sub.2 (1:1) in situ 6 1) TES-AlCl.sub.3—i- 5 h, 90° C. menthone 99 90 PrOH (1:0.3:0.6) 2) ZnCl.sub.2 (1 equiv) 7 TES-AlCl.sub.3—EtOH 3 h menthone 94 61 (3:0.3:0.6) 8 TES-FeCl.sub.3—i-PrOH 3 h menthol 100 28 (3:0.3:0.6) 9 PMHS-FeCl.sub.3—i- 3 h menthone 83 67 PrOH (3:0.3:0.6)

[0214] It is important to note that the adducts PMHS-AlCl.sub.3-i-PrOH (3:0.3:0.6) and TES-FeCl.sub.3-i-PrOH (3:0.3:0.6) enable one-pot preparation of menthol from pulegone.

Example 10

Preparation of 2-pentylcyclopentanone

[0215] ##STR00032##

[0216] 8.2 μL (0.05 mmol/1 equivalent/TES) of enone are added to the adduct triethylsilane-AlCl.sub.3-iPrOH (molar ratio 1:0.3:0.6) prepared in cyclopentyl methyl ether and the solution is stirred at 80° C. for 3 hours. At the end of the reaction, 2-pentylcyclopentanone is obtained with a selectivity of 100%. No trace of ether or of cyclopentanol is observed.

[0217] The same reaction, performed with an adduct triethylsilane-FeCl.sub.3-iPrOH (molar ratio 1:0.3:0.6), triethylsilane-FeCl.sub.3-iPrOH (molar ratio 2:0.3:0.6), triethylsilane-FeCl.sub.3-iPrOH (molar ratio 1:0.5:0.6) or an adduct triethylsilane-FeCl.sub.3 (molar ratio 2:0.3) leads to the formation of 2-pentylcyclopentanone with a conversion of 67, 84, 78 and 80% and a selectivity for the ketone greater than 90%.

[0218] The results with the adducts of iron trichloride and aluminium trichloride are summarised in table 6:

TABLE-US-00009 TABLE 6 Select. Conv. Adduct Conv. (%) (%) (%) Select. (%) t (h) TES-AlCl.sub.3—i-PrOH 74 97 87 100 4 h (1:0.3:0.6) TES-FeCl.sub.3—i-PrOH 18 100 67 100 3 h (1:0.3:0.6) TES-FeCl.sub.3—i-PrOH 70 100 84 90 3 h (2:0.3:0.6) TES-FeCl.sub.3—i-PrOH 7 93 78 100 3 h (1:0.5:0.6) TES-FeCl.sub.3 (1:0.3) 5 nd 80 100 4 h TES-FeCl.sub.3 (2:0.3) 63 100 80 100 4 h

Example 11

Preparation of Cyclohexanol from Cyclohexanone

[0219] ##STR00033##

[0220] 4.9 mg (0.05 mmol, 1 equivalent/TES) of cyclohexanone are added to the adduct triethylsilane-ZnCl.sub.2 (molar ratio 1:1) prepared in 50 μL cyclopentyl methyl ether and the solution is stirred at 90° C. for 4 hours. At the end of the reaction, cyclohexanol is obtained with a selectivity of 100%.

Example 12

Preparation of 2-dodecanol by Reduction of 2-dodecacone

[0221] ##STR00034##

[0222] 11.2 μL (0.05 mmol, 1 equivalent/TES) of cyclohexanone are added to the adduct triethylsilane-ZnCl.sub.2 (molar ratio 1:1) prepared in 50 μL of cyclopentyl methyl ether and the solution is stirred at 90° C. for 3 hours. At the end of the reaction, cyclohexanol is obtained with a selectivity of 100% and a conversion rate of 75%. No trace of ether or of dodecane is observed.