Selenols, alkyl

As well as acylation of selenols, alkylation of selenocarboxylates with alkyl halides is one of the most straightforward methods for synthesis of selenol esters. However, known examples of selenol esters synthesized using this strategy have been limited to a few cases, due to the difficulty of the preparation of selenocarboxylates. 

Hydrozirconation of terminal alkynes R-C=CH (R= aryl, alkyl) with 1 affords terminally ( )-Zr-substituted alkenes with high efficiency and excellent stereochemical and regiochemical control (>98%). These alkenylzirconocene complexes are of particular interest for synthetic use [136, 143, 144]. Moreover, beside the electropositive halogen sources [145] and heteroatom electrophiles [3] used in the pioneering studies to directly cleave the Zr-C bond, ( )-vinyl-Zr complexes were recently transformed into a number of other trans-functionalized alkenes such as ( )-vinyl-sul-fides[146], vinylic selenol esters [147], vinyl-sulfones [148], vinyl-iodonium [149], vinyl-(R0)2P(0) [150], and vinilic tellurides [143]. 

Alkyl phenyl setenides selenol esters. N-PhcnylscIcnophthalimidc is superior to aryl selenocyanates for conversion of alcohols to alkyl phenyl selenides (6, 252-253) and of carboxylic acids to selenol esters (7, 396-397). When conducted in the presence of an amine the latter reaction provides amides in high yield (equation l). ... 

The 4-(2-hydroxyaryl)-l,2,3-selenadiazole 56 undergoes ready decomposition by the action of potassium carbonate to form benzofuran-2-selenolate 177. The intermediate 176 can be alkylated with methyl iodide and benzyl chloride and arylated with 2,4-dinitrochlorobenzene (Scheme 14) <2001RJ01643, 2000RJ0605, 1999TL3903>. Intermediate formation of 2-(o-hydroxyphenyl)ethyneselenolate 174 during decomposition of 1,2,3-selenadiazoles was proven by... 

Depending on the nature of the R groups of the alkynyl selenides 99, vinylic species with different regio- and stereochemistry are obtained (Scheme 62). When R is an alkyl group, mixture of products of different regiochemistry is obtained,179 which makes this method unsuitable for the preparation of this class of compounds. A solution for this problem consists in the use of lithium alkynyl selenolates 102 as precursors of the vinylzirconium species 103, as shown in Scheme 63.1... 

Carbonsulfur bonds can be formed by the reaction of elemental sulfur with a lithio derivative, as illustrated by the preparation of thiophene-2-thiol 446. If dialkyl or diaryl disulfides are used as reagents to introduce sulfur, then alkyl or aryl sulfides are formed sulfinic acids are available by reaction of lithium derivatives with sulfur dioxide. In the pyrrole series, a 2-thiol and the corresponding selenol can be prepared via reaction of 2-lithio-l-methylpyrrole with sulfur or selenium, then trapping with Me3SiCl leading to the 2-Me3SiX-substituted derivatives <1997T13079>. 

An interesting variation for the introduction of selenenyl species, which has the advantage of using cheaper elemental selenium, has been described by Liotta and cowoiicers (Scheme 17). This reaction involves conversion of the lithium enolate (21) to the intomediate selenolate (22) which may be directly alkylated to give the selenenyl derivative (23) in high yield. The reaction worits well with ketones, esters and 3-dicarbonyl compounds, but has the disadvantage of requiring the use of HNiPA. ... 

Alkyl selenides are most conveniently prepared by the dialkylation of Na2Se or by the monoalkylation of selenolates. Common routes to aryl derivatives include the reaction of a selenolate with a diazonium salt, the SrnI reactions described earlier, and the reaction of aryUithiums with aryl selenocyanates (ArSeCN). A different approach employs the reaction of alcohols with aryl selenocyanates or N-(phenylseleno)phthalimide (see Section 6) in the presence of tri-n-butylphosphine. Similar conditions can also be used to convert carboxylic acids to selenoesters (8). These reactions are illustrated in Scheme 3. 

Diselenides are generally prepared by the aerial oxidation of selenols or selenolates (see Section 2) or by the reaction of Li2Sc2, Na2Se2, or other 802 species with alkyl or aryl halides. In the latter case, elevated temperatures and DMF as the solvent are recommended. Aryl diselenides may also be obtained from the reaction of 802 with diazonium salts (Scheme 6). Relatively few unsymmetrical diselenides have been reported. Triselenides are also known but have not been as widely studied. 

This naked selenolate is more reactive than the one complexed with borane 1 [1]. For example, in the presence of HMPA, 4 undergoes an SN2-type ester cleavage to produce the corresponding acids and alkyl phenyl selenides (Sect. 3.3) [6 a]. Uncomplexed selenolate 4 can also be prepared by the reduction of benzeneselenol (PhSeH) with sodium hydride (NaH) (Scheme 4b) [6aj. 

Substitutions to halide compounds are the most typical reactions of nucleophilic selenium species (Scheme 18). Alkyl or aryl selenolates (R SeM), which are prepared in situ by the methods described in Sect. 2, react with halides to give... 

Two interesting applications of this type of reaction are presented in Schemes 19 and 20. Selenium-substituted cysteine (selenocysteine) derivatives are synthesized by condensation between selenocysteine and the corresponding alkyl and benzyl halides or between areneselenolate and j0-chloroalanine (Scheme 19) [31]. These compounds are considered as potential kidney selective prodrugs of biologically active selenol compounds. 

From aziridines. N-Tosylaziridines, easily obtained by aziridination of the corresponding alkenes, can be opened by selenolate reagents and furnish, after straightforward N-alkylation, radical precursors suitable for the preparation of pyrrolidine derivatives [12]. The preparation of octahydro-lff-indole 24 is shown in Eq. (4). A competing process involving radical azi-doselenenylation of alkenes has also been developed and will be discussed later (Sect. 5.2). 

One of the most general methods for synthesis of selenol esters uses dimethylaluminum methylseleno-late (16), which has been found to be a remaiicably efficient and versatile reagent for the conversion of O-alkyl esters to their corresponding methylselenol esters under mild conditions. The reagent (16) is conveniently prepared by heating a toluene solution of trimethylaluminum with powdered selenium for 2 h under reflux. TTie transformation of various esters to selenol esters can be completed within 1 h. Representative results are shown in Scheme 6 (17-23). This method can also be applied to cyclic esters U ) and esters (20)-(23) containing other functional groups. 

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