Lithium transmetalation

In the initial studies about the reaction of /V.zV-disubstituted formamides with alkaline metals to give glyoxylic amides, the participation of carbamoyl metal derivatives as intermediates was postulated83. The first preparation of the carbamoyllithium 77 was described two years later by a mercury-lithium transmetallation from compound 76 at —75 °C (Scheme 20)84. The authors proposed also an aminocarbene structure 78 and studied its reactivity with methanol, methyl iodide, carbonyl compounds, esters, acyl chlorides, mercury(II) chloride and tri-n-butyltin chloride providing compounds 79. 

Carbamoyllithiums can be prepared by four general methods (a) Lithium amides car-bonylation (b) deprotonation of formamides with alkyllithiums (c) tellurium-lithium or chlorine-lithium exchange and (d) tin-lithium transmetallation. 

Finally, the carbamoyllithium 122 was prepared by tin-lithium transmetallation at —105 °C from the corresponding carbamoylstannane 121. This tin compound was prepared by addition of tri-n-butyltin lithium to an isocyanate followed by quenching with SEMC1 [2-(trimethylsilyl)ethoxymethyl chloride]. The functionalized intermediate 122 was acylated with the ester 123 to give the product 124 in a model study towards the synthesis of mycalamides (Scheme 33)115. 

For the fast ge/w-dialkylation of 1,3-dithiane dianion, tin-lithium transmetallation at the 2-position of dithiane is a much faster process than the corresponding deprotonation. 2,2-Bis[tri(n-butyl)stannyl]dithiane (175)223 can be alkylated sequentially it was trans-metallated with n-BuLi at —78 °C, after 5 minutes treated with the first alkyl halide and after 10 more minutes the process was repeated providing dialkylated products224. This strategy has been used in the total synthesis of (—)-perhydrohistrionicotoxin, namely preparing the key compound 178 employing successively iodides 176 and 177 as electrophiles (Scheme 50)224. 

Alkyl substituted a-lithiodihydrofurans 599-602 and a-lithiodihydropyrans 603-606 have been used for natural product synthesis. They are prepared by deprotonation of the corresponding DHF or DHP derivatives with f-BuLi in THF at —78 to 0 °C. Lithiated DHP 606 has been prepared by tin-lithium transmetallation starting from the hemiacetal 607, by successive transformation into the sulfone 608907 and the stannane 60 9908 (Scheme 163). 

An example prepared by tin-lithium transmetallation is compound 637, which reacts with enolizable ketones, after transmetallation with cerium(III) chloride895. This intermediate was transformed into the corresponding vinylzinc reagent and, after palladium(O)-catalyzed cross-coupling reactions with aryl iodides, was used in the synthesis of the antitumor antibiotic rineomycinone B2 methyl ester940,941. The vinyllithium 627 has also been transformed into the corresponding vinyl iodide by stannylation followed by reaction with iodine. The arylation has been performed in this case by a palladium(0)-catalyzed... 

Intermediates 663 can be prepared by tin-lithium transmetallation with w-BuLi from a-stannylated vinyl sulfides974. Starting from l,l-bis(arylsulfanyl)ethenes, a reductive metallation with lithium naphthalenide at —70°C is a very efficient approach to lithiated vinyl sulfides975,976. Other methods involved bromine-lithium exchange977 or addition of methyl or phenyllithium to thioketenes978. A convenient method for the preparation of l-(methylsulfanyl) and l-(phenylsulfanyl) vinyllithiums was the treatment of 2-methoxyethyl sulfides with 2 equiv of w-BuLi-TMEDA at — 30 °C979. 

Vinyl selenides have been lithiated at the a-position by LDA983,984 at —78 °C in THF to give a-(arylselanyl)vinyllithiums 680, a-(methylselanyl)vinyllithiums 681 being obtained by selenium-lithium transmetallation from l,l-bis(methylselanyl)alkenes with n-BuLi in THF or t-BuLi in ether at —78 °C985 986. These intermediates reacted with alkyl halides, epoxides, carbonyl compounds and DMF985, the final deprotection being performed by mercury(II) salts986. 

In organic synthesis, the preparation of most vinylstannanes is aimed at tin/lithium transmetallation (equation 8-33), or at Stille coupling reactions (equation 8-34). These reactions are discussed in Sections 22.1 and 22.2, respectively, and the remaining reactions are covered in this section. 

Many of the applications of organotin compounds are specific to one class of compounds (e.g. tin hydrides or allylstannanes) and these topics are covered in the corresponding chapters. On the other hand, reactions involving tin/lithium transmetallation, or palladium-catalysed coupling, can be carried out with a variety of types of organostannanes, and these reactions are collected together in this chapter. These topics have an extensive literature that is beyond the scope of this book, and the treatment here is limited to an outline of the fields, and a guide to the literature. 

In Section 19.1 we have seen that tetraorganostannanes react reversibly with organoli-thium compounds by tin/lithium transmetallation via anionic 5-coordinate trigonal bi-pyramidal intermediates. 

Organic Synthesis Tin/lithium Transmetallation, the Stille Reaction... 

This phenomenon suggests that a nitrogen lone pair plays an important role in tin-lithium transmetalation in which a synclinal relationship is required between the nitrogen lone pair and the carbon-tin bond. 

Alkenyllithium compounds can also be prepared by metallation of alkenes, particularly when alkenyl hydrogens are rendered acidic by an a-substituent (equation 22). Transmetallation of alkenyl stannanes with organolithium reagents gives alkenyllithium compounds with retention of alkene stereochemistry (equation 23). Tin-lithium transmetallation has been used to prepare 1,4-dilithio-l,3-butadiene. Monosubstituted alkenyllithium compounds RHC=CHLi, can also be prepared from the corresponding diorganotel-luride, RHC=CHTeBu, by reaction with butyllithium in... 

A Vnsh coupling of 24 Hz has been observed by Santiago et in the spectrum of trans-4-terf-butyl-2-(tributylstannane)piperidine but not in that of its cis isomer. In the first case the lone nitrogen pair and the C-Sn bond are eclipsed, in the other antiplanar. The authors also noticed that the tin-lithium transmetallation proceeds very easily for the trans compound, whereas isomer cis does not undergo this process. 

Aminomercurated olefins also undergo mercury-lithium transmetallation to give the dianions (8), which react with a variety of electrophiles to give substituted secondary arylamines (Scheme 15). o-Alkylated arylamines are the products of the reaction of arylaminodivinylboranes with acetylene derivatives."... 

Functionalized organolithium compounds of type XI can be accessible through a large number of methodologies. They are accessible by halogen-, sulfur-, or selenium-lithium exchange, tin-lithium transmetallation, reductive opening of four-membered heterocycles and also by carbolithiation of cinnamyl systems. 

The allylic intermediate 157 was prepared by deprotonation with LDA and reacted with 1,2-dialkyloxiranes in the synthesis of parasorbic acid [132], Direct deprotonation of silyl ally] ether with s-BuLi gave the allylic compound 158, which reacted with electrophiles at the y-position [133]. Tin-lithium transmetallation of a 3-stannylated enamine led to the intermediate 159, which after reaction with electrophiles and acidic hydrolysis gave 3-funcionalized cyclohexenones [134], The chiral mdo-aminoallyllithium 160 was also prepared by tin-lithium transmetallation of the corresponding O-methylprolinol derivative, and alkylated to give after hydrolysis /3-alkylated ketones [135]. Direct deprotonation with t-BuLi of N-methal-lylaniline gave the dianionic intermediate 161, of type XIV [136]. 

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