β-Butyltellanyl Carbonyl Compounds : A Useful Source of Masked Metal Homoenolates

Homoenolate anions are important synthons in the Umpolung concept. Unlike the enolate anions, the homoenolate anions cannot be stoichiometrically generated by deprotonation of a carbonyl compound, since the pk a value of the β-hydrogen is only very slightly lowered. In addition, the reactive homoenolates 1, especially lithium and sodium derivatives, spontaneously cyclize to the corresponding cyclopropanolate tautomer 2 (Scheme 1), which does not react as a carbon-nucleophile with standard electrophiles.


Introduction
Homoenolate anions are important synthons in the Umpolung concept. 1 Unlike the enolate anions, the homoenolate anions cannot be stoichiometrically generated by deprotonation of a carbonyl compound, since the pk a value of the β-hydrogen is only very slightly lowered. 2 In addition, the reactive homoenolates 1, especially lithium and sodium derivatives, spontaneously cyclize to the corresponding cyclopropanolate tautomer 2 (Scheme 1), 2 which does not react as a carbon-nucleophile with standard electrophiles.
Although the α-enolization of carbonyl compounds is readily carried out under mild conditions to yield high equilibrium concentrations of α-enolates, vigorous conditions are required to give low concentrations of shortlived intermediate homoenolates by β-deprotonation of nonenolizable ketones. 2 This fact makes the direct βdeprotonation of carbonyl compounds an impracticable method for preparative purposes.The use of a masked carbonyl unit is an alternative to circumvent this problem. 3wever, this strategy is also limited to the presence of strongly electron-attracting substituents at the β-position to the masked carbonyl groups that promotes the stabilization of the carbanion formed.Classically, for this purpose nitro, 4 phosphorus 5 and sulphur 6 based compounds are used.Moreover, this method requires previous preparation of the nitro, phosphorus or sulphur organic substrates and another further step, to remove reductively the activating group.
A simple strategy to circumvent this problem should be the preparation of β-butyltellanyl masked carbonyl compounds such as 3, 7 and their transformation into the corresponding lithium homoenolates through a tellurium/ lithium exchange reaction (Scheme 2). 8general way to obtain compounds of type 3 should be the Michael addition of n-butyltellurol to α,βunsaturated ketones, as recently described by us, 9 followed by a ketalization reaction.
The n-butyltellurol, generated in situ by reaction of elemental tellurium with n-BuLi in THF, followed by addition of a proton source such as ethanol or water, reacts rapidly with Michael acceptors. 9Under these conditions the β-butyltellanylketones 5 and 6 were successfully prepared in 86% and 89% yield respectively (Scheme 3).The β-butyltellanylketones 5 and 6 were converted into the corresponding β-butyltellanylketals 3 and 7 in high yields by reaction with ethylene glycol in benzene in a Dean-Stark apparatus (Scheme 4). 9,10e light yellow tellurides 3 and 7 were transformed into the corresponding lithium masked homoenolates by reaction with t-butyllithium in THF at -70 °C.The tellurium/lithium exchange showed to be very fast even to generate a secondary anion.
Trapping the lithium anions with benzaldehyde afforded the corresponding alcohols 8 and 10 (Scheme 5). 11The lithium intermediates were also submitted to reaction with the copper soluble species CuCN.2LiCl 12 producing the corresponding higher order cyanocuprates. 13ichael addition of these intermediates to 2-cyclohexen-1-one produced the corresponding saturated ketones (Scheme 5). 13ll tellurides described in this paper are stable to the ambient light and can be manipulated in the air.Most of them are almost odourless or present a smell not more unpleasant them most of the laboratory chemicals normally used in an organic synthesis laboratory.
It is worthy of note that the dibutyltelluride originated in the tellurium/lithium exchange step, is totally compatible with all the subsequent operations.It can be easily eliminated in an odourless operation by washing the organic phase with a diluted sodium hypochlorite solution.
In conclusion, β-butyltellanyl carbonyl compounds are a very practical source of homoenolate equivalents.
13.Typical procedure to prepare the higher order cyanocuprate and its reaction with 2-cyclohexen-1-one: To a solution of the lithium anion of telluride 7 (1 mmol, 0.32 g, generated by the same procedure described in ref. 11) at −70 0 C, was added a solution of CuCN.2LiCl (0.5 mmol, 1 mol −1 / THF, 0.5 Equiv.).The resulting orange solution was stirred for 20 min at the same temperature and then 2-cyclohexen-1-one (1 Equiv.) was added in one portion.The resulting solution was stirred for 1 h at −70 o C and then allowed to warm to 0 o C. A solution of saturated aqueous ammonium chloride and ammonium hydroxide was added (3 mL) and the mixture was stirred for 40 min.The organic phase was sequentially washed with a diluted solution of sodium hypochlorite (2 x 5 mL) and then with brine (2 x 10 mL), dried over magnesium sulphate, filtered and the solvents were removed.The residue was purified by silica gel chromatography using a 3:1 hexane:ethyl acetate mixture, to give a diastereomeric mixture of 3-(1,4-Dioxaspiro[4.5]dec-7-yl)-cyclohexanone (11