Reactions with selenium-stabilized carbanions

Azocanes with nitrogen at a bridgehead such as fused azocane 289 were prepared starting from /V-protected amino aldehydes 286. Those amino aldehydes were converted into allylic alcohols by the classical Morita-Baylis-Hillman reaction or by condensation with selenium-stabilized carbanions, followed by oxidation <2007JOC5608>. Fused azocane 289 was prepared in good yield as described in Scheme 120. Formation of [ z, ,0]-bicyclic structures via these reactions is general and the stereochemistry of the starting amino-aldehyde is preserved. 

Various applications of selenium-stabilized carbanions in synthesis have been reported. The mixed acetal 108 derived from benzaldehyde was efficiently metalated by KDA in THF. The a-methoxy-a-methylselanyl benzyl-potassium compound 109 is stable at low temperatures (—78 °C) and reacted with a variety of electrophiles. The reaction products 110, still mixed acetals, are obtained in good yields as shown in Table 3 (Scheme 25).196... 

The addition of a selenium-stabilized carbanion to an electrophile can be followed by another reaction as selenones are good leaving groups. a-Selenonylalkyl compounds 111 can be deprotonated using potassium tert-butoxide. Reactions with a,/ -unsaturated / r/-butyl esters lead to cyclopropane derivatives 112 in good yields (Scheme 26).197... 

The formation of /3-hydroxyselenides through the reaction of a selenium-stabilized carbanion with carbonyl compounds has been extensively used also in the context of natural product synthesis. The phenylselenoalkyllithium compound 115 was reacted with aldehyde 116 to afford /3-hydroxyselenide 117. In a radical cyclization cascade the tricyclic molecule 118 was generated in good yields and subsequent transformations led to the synthesis of pentalenene 119 (Scheme 28).1 9 Also other natural products like zizaene and khusimone have been synthesized via a similar route.200... 

Selenium-stabilized carbanions can be also generated by 1,4-addition of nucleophilic reagents to a-selanyl a,[3-unsaturated carbonyl compounds. The conjugate addition of trialkylsilyllithium compounds to 133, followed by reaction with allyl iodide, afforded the addition products 134 with good m-stereoselectivity (R = Me dr 86 14 R = Ph dr 94 6) (Scheme 34).214 The addition of lithium dialkylcuprates to 2-phenylselanylcycloalk-2-enones has also been used for the synthesis of natural products.215,216... 

The formation of -hydroxy selenides through reaction of a selenium-stabilized carbanion with a carbonyl compound has been extensively used, in particular for the synthesis of natural products [1 - 4, 33]. The most recent... 

Such a propensity of the carbon-selenium bond to be transformed into a carbon-lithium bond on reaction with butyllithiums has in fact been used successfully for the synthesis of various (x-selenoalkylmetals from phenyl and methyl selenoacetals. It has inter alias been used for the synthesis of those ot-selenoalkylmetals which bear two alkyl groups on the carbanionic center and which are expected to be the less stabilized ones It also permits the selective synthesis of a-lithioseleno-... 

Reaction of alkyl metals with selenides and functionalized selenides 2.6.2.12 Stabilization of carbanionic centers by selenium-containing moieties... 

As a general mle, unless an anion-stabilizing group, such as phenyl, or a heteroatom such as sulfur is present, the alkylsilane is not readily deprotonated. The a-halosilane can be deprotonated but, unlike the readily available chloromethyltrimethylsilane, there are few general methods to this approach. Al-kyllithium reagents add to vinylsilanes ( ) to produce the carbanion (287). Silyl derivatives with heteroatoms, such as sulfur, selenium, silicon or tin, in the a-position (288) may be transmetallated (Scheme 41). Besides the difficulty in synthesizing the anion, alkene formation lacks specificity for simple di- and tri-alkyl-substituted alkenes. As a result, the Peterson reaction of an a-silyl carbanion with a carbonyl has found the greatest utility in the synthesis of methylene derivatives, (as discussed in Section 3.1.3), heterosubstituted alkenes and a,p-unsaturated esters, aldehydes and nitriles. 

The species (10) and (11), may be considered as synthons for HSCH2 and H0(CH2) CH2 respectively, whilst (12) reacts with aldehydes and ketones to give oxiranes. Selenium is capable of stabilizing an adjacent carbanion centre in the same way as sulphur, and reaction of diselenoketals with Bu"Li provides a convenient approach to reagents of type (13). After alkylation, hydroxyalkylation, or acylation of (13) the selenium can be removed reductively, by oxidative elimination, or, in the case of 2-hydroxy compounds, by elimination to form an oxirane, so the synthetic potential is clear. 

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