A-Selenoalkyllithiums

A general method has been elaborated for the synthesis of oxetanes from oxiranes by means of carbene insertion, with an a-selenoalkyllithium reagent that has also been utilized for the regioselective preparation of the oxirane itself from a carbonyl compound (Eq. 185). ... 

Synthesis of a-selenoalkyllithiums by selenium-lithium exchange 2.6232 Synthesis of a-selenovinyl metals by selenium-metal exchange... 

For the synthesis of a-selenoalkyllithiums, the selenium-lithium exchange reaction is a good alternative to the almost impossible metallation of unactivated selenides.Thus it has been found that a large variety of selenoacetals, often readily available from carbonyl compounds and selenols, react with butyllithiums to provide a-selenoalkyllithiums - in very high yields (Scheme 2 see also Section 2.6.2.3). 

It also has been found that butyllithiums react faster with 2,2-bis(phenylseleno)propane than with its methylseleno analog. Thus, addition of n-butyllithium to a 1 1 mixture of 2,2-bis(phenylseleno)propane and 2,2-bis(methylseleno)propane leads selectively to the formation of 2-lithio-2-phenylselenopropane under kinetically controlled conditions, providing the a-selenoalkyllithium with the more stable caibanionic center (Scheme 4). Furthermore, 2-methylselenopr(q)yUithium reacts with 2,2-bis(phenyl-seleno)propane and leads, under thermodynamically controlled conditions, to 2-phenylseleno-2-propyl> lithium, thus demonstrating the better propensity of a phenylseleno moiety over a methylseleno moiety to stabilize a carbanionic center (Scheme 5). 

Yet another important difference of reactivity towards n-butyllithium has been found between phenyl selenoacetals derived from aldehydes and ketones. This distinction allowed, when the reaction was performed in ether-hexane, the selective synthesis of an a-selenoalkyllithium derived from the phenyl selenoacetal of an aldehyde in the presence of the phenyl selenoacetal of a methyl ketone, which remained untouched (Scheme 11). ... 

Phenyl and methyl selenoacetals usually react widt butyllithiums and produce die conesponding a-selenoalkyllithiums and butyl selenides.A Ai2,i3.i6,i7353 .48-50,S4,35,60,i58 j jg reaction is usually carried out at -78 C (a temperature at which these oiganometallics are stable for a long period), widi n-butylli-thium in THF or s-butyllithiiun in edier. It provides a large variety of a-selenoalkyllitUums inclu g... 

In general, the Se-Li exchange is easier (i) when carried out in THF rather than in ether, (ii) when s-or r-butyllithium is used instead of n-butylli um. Methyllithium is almost unreactive in most cases and (iii) if a better stabilization of the carbt onic center can be achieved. Thus phenyl selenoacetals react more rapidly than their methyl analogs (see Section 2.6.2.1.2), and a-selenoalkyllithiums where the carbanionic center is part of a three-membered cycle or is substituted by an aryl group are more readily obtained than those which are monoalkyl or dialkyl substituted. 

Except for the case shown in Scheme 83, a-selenoalkyllithiums are stable intermediates at or below -78 They do not have a high tendency to decompose to carbenes (Scheme 84, a), nor are... 

Reaction of n-butyllithium with l,l-bis(seleno)-4-f-butylcyclohexane, l,l-bis(methylseleno)-2-methylcyclohexane or l,l-bis(phenylseleno)-3-silyloxybutane leads to, in each case, one of the stereoisomers of the a-selenoalkyllithium, as observed by Se NMR and trapping experiments (Scheme 86). In the former case, the reaction exclusively produces the axially wiented lithio d vative and in the latter case it leads almost exclusively to the stereoisomer shown in Scheme 86. It has been secured in the case of l,l-bis(seleno)-4-r-butylcyclohexanes, that the C—Se bond cleavage is operating stereoselective-ly on the axial seleno group. 

Only a few functionalized a-selenoalkyllithiums have been synthesized apart from the ones shown in Schemes 11, ° 79 and 86. 

The same type of exchange occurs,but unexpectedly more r idly and at -78 "C, with the a-selenoalkyllithium shown in Scheme 83. At higher temperature (20 the addition of the... 

The reactions of a-selenoalkyllithiums with aliphatic and aromatic aldehydes and ketones are not usually stereoselective regardless of the solvent used (ether or THF). Even in the most favorable cases, such as that of l-methylseleno-2,2-dimethylpropyllithium and heptanal, in which well-diffeiendated bulky groups are involved, the stereoisomeric ratio ranges from 1 1 to 3 2 (Scheme 124). - However, in the case shown in Scheme 86, b, in which the lithium can coordinate to the silyloxy group, only one of the two stereoisomeric 3-hydroxyalkyl selenides is formed. 

C—SeMe and the C—Cl bonds and often faster than that of the C— Br bond The reduction is highly chemoselective and leads to alcohols usually in almost quantitative yield (Scheme 161, a Scheme 164, a Scheme 168, a and b). In rare cases, however, such as when a ca n-carbon double or triple bond is present in a suitable position, the formation of a five- or six-membered ring takes place by trapping of the radical intermediate (Scheme 118). ° Tin hydride reduction has been advantageously extend (g P-hydroxy-y-alkenyl and -hydroxy-a-alkenyl selenides displayed in Scheme IM (a) and Scheme 168 (a and b) and derived from a-selenoalkyllithiums and enenones, and from 1-seleno-l-alkenyl metals and carbonyl compounds, respectively. 

The combination of reactions described above (Sections 2.6.4.2 to 2.6.4.5) allows the selective synthesis of a large variety of alcohols, allyl alcohols, alkenes, epoxides and carbonyl compounds from p-hydroxyalkyl selenides. These products often can be obtained from two ca nyl compounds by activation of one of them as an a-selenoalkyllithium (Schemes 161-196). 

The whole process involving the reaction of an a-selenoalkyllithium with a carbonyl compound and further reduction of the C—Se bond in the resulting -hydroxyalkyl selenide leads to an alcohol which can be directly produced from an alkyl metal and the same carbonyl compound (Section 2.6.4.2). This two-step procedure offers, in some cases, interesting advantages due to the larger size of a-selenoalkyl-lithiums, which favors a better stereochemical control (see, for example. Scheme 167 for comparison between the two approaches). °... 

Aldiough in many instances the well-established, one-step procedures presented above are very efficient and should be preferred to the a-selenoalkyllithium route, there remain several cases for which the latter approach offers definite advantages. 

The high nucleophilicity of a-selenoalkyllithiums towards carbonyl conqiounds, even those that are the most hindered or enolizable, such as 2,2,6-trimethyl- and 2,2,6,6-tetramethyl-cyclohexanone (Schemes 113 and 164), di-t-butyl ketone, pennethylcyclobutanone, peimethylcyclopenta-none (Schemes 113 and 187) °- and deoxybenzoin (Schemes 115, 116 and i65y 4 49 23 iqws the synthesis of related alkenes, epoxides and rearranged ketones which are not available from the same carbonyl compounds on reaction with phosphorus or sulfur ylides - or diazoalkanes. ... 

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