Carbamates lithiation

Table 5. 2-Oxo-3-alkcnyl Carbamates from Addition of Lithiated 1-(4-Mc-thylphenylsulfonyl)-2-alkenyl Carbamates to Chiral Aldehydes3...

Z)-3-Alkoxyallylstannanes of high optical purity are available by stannylation of lithiated allyl carbamates derived from optically active allyl alcohols118. 

With titanated 2-alkenyl carbamates, the opposite regioselectivity can also be observed. Lithiated l-(4-methylphenylsulfonyl)-2-alkenyl diisopropylcarbamates, after metal exchange with chlorotriisopropoxytitanium, add to aldehydes y-selectivelylls. The less reactive titanat-ing reagent tetraisopropoxytitanium does not apparently react with these stabilized lithium carbanions, because in its presence a-selectivity is retained (Section 1.3.3.3.1.3.2.). 

Lithiated allylic carbamates (35) (prepared as shown) react with aldehydes or ketones (R C0R ), in a reaction accompanied by an allylic rearrangement, to give (after hydrolysis) y-hydroxy aldehydes or ketones. The reaction is called the homoaldol reaction, since the product is a homolog of the product... 

Lithiation of alkyl groups is also possible and again a combination of donor chelation and polar stabilization of anionic character is required. Amides and carbamates can be lithiated a to the nitrogen. 

Studies with bicyclic carbamates of general structure 1 indicated that proximity and alignment of the carbonyl oxygen to the lithiation site is a major factor in determining the rate of lithiation.59... 

Bicyclic structures of this type are more reactive than monocyclic or acyclic carbamates, indicating that a relatively rigid orientation of the carbonyl group is favorable to lithiation. Substituted formamidines can also be lithiated.60... 

Transmetalation with Zn on a chiral lithiated alkyl carbamate had been reported by Taylor via addition of a solution of ZnCl2 to an in situ generated chiral organolithium (Scheme 8.10) [15]. 

A second route to nonracemic /-oxygenated allylic stannanes utilizes an enantioselective deprotonation of allylic carbamates by BuLi in the presence of (—)-sparteine. The configurationally stable a-lithio carbamate intermediate undergoes enantioselective S/,-2 reaction with Bu3SnCl and Mc SnCI (Scheme 28)65. Once formed, the /-carbamoyloxy stannanes can be inverted by successive lithiation with. s-BuLi and stannation with R3SnCl (Scheme 29)65. The former reaction proceeds with S/.-2 retention and the latter by Sf2 inversion. Nonracemic allylic carbamates can also be used to prepare chiral stannanes. Deprotonation with. s-BuLi TMEDA proceeds stereospecifically with retention (Scheme 29)65. 

The mechanism of the stereoselective syntheses of (K)-3-aryl-5-(hydroxy-methyl)oxazolidinones via the Mannenin reaction of aryl carbamic acid esters with (Jt)-glycidyl butyrate has been explored in detail by Brickner et al. [60]. Namely, N-lithiated carbamate derivatives of anilines are allowed to react with the commercially available (K)-glycidyl butyrate (96-98% enantiomeric excess ee) under appropriate conditions to obtain enantiomerically pure (Jt)-3-aryl-5-(hydroxymethyl)oxazolidinones in 85-99% yields, according the pathways depicted in Scheme 19. 

The (-)-sparteine-mediated lithiation of achiral propargyl carbamates with wBuLi and allene synthesis has already been described in Section 4.2.7 [84],... 

In recent years, Hoppe s group has considerably extended the isomerization-addition methodology, especially for the highly regio- and stereoselective synthesis of 1,2-alkadienyl carbamates. It involves deprotonation of alkynyl carbamates, transme-talation into a titanium species and subsequent reaction with carbonyl compounds [26-30]. This group recently described the preparation of enantiomerically enriched 4-hydroxyallenyl carbamates 22 by sparteine-mediated lithiation of alkynyl carbamates 20 [29]. Impressive examples of these transformations are summarized in Scheme 8.8. 

The lithiated propargyl carbamate is configurationally stable at -78 °C as long as a bulky substituent (R1) is present at the remote alkynyl position. 

Carbamates also serve as satisfactory starting materials for this methodology (Eq. 9.42) [49]. In this variation, lithiation of the carbamic amide precedes displacement by the cuprate reagent. 

BuLi-TMEDA , are similarly powerful directors (Scheme 54). By contrast, the related amides, carbamates and ureas (125, R = COAr, CONR2, CO2R) usually undergo ben-zylic a-lithiation (see Section II.B). The bias can be shifted towards ortholithiation by additional electron-withdrawing substituents on the ring . 

The carbamates 549 (R = OBu-f) behave similarly, though they must be lithiated with i-BuLi to avoid addition to the carbonyl group °. It is possible simply to use a lithium carbamate to protect an amino group during a lateral lithiation an initial deprotonation and carbonation generates the lithium carbamate 556, which is then deprotonated twice more by t-BuLi (Scheme 220). After electrophilic quench, acid hydrolysis of the carbamic... 

The reduced electrophUicity of indole-3-carboxylic esters (they are vinylogous carbamates) means that they are much more versatile directors of lateral lithiation than the comparable benzoates, as illustrated by the synthesis of 564 (Scheme 221... 

In aromatic compounds, potent but frustrated (their ortho positions blocked) directing groups may lead to lithiations at positions other than ortho. For example, when the carbamate 610 is treated with LDA in refluxing THE, lithiation occurs at a remote position (not peri, note) and an anionic Fries rearrangement ensues to give 611 (see Section I.B.l.d). Lactonization gives 612 (Scheme 239). ... 

Carbamate 613 under the same conditions also undergoes remote lithiation and a remote anionic Fries rearrangement, and then the product amide 614 proceeds to direct a remote benzylic lithiation, even though it has a free ortho position. Finally, the benzylic organo-lithium 615 cyclizes onto the amide to form 616—all in one pot (Scheme 240) . 

Numerous structures of a-lithiated amines, amides, carbamates as well as a-lithiated thioethers, sulfoxides, sulfones and sulfonamides have been determined. Although a slight... 

Configurational stability has also been confirmed for various metalated carbamates by Hoppe and coworkers. Remarkably, carbamate-protected alcohols such as 20 are deprotonated enantioselectively, when treated with i-butyllithium in the presence of (—)-sparteine. The lithium carbenoids like 21 (R = alkyl) thus generated turn out to retain their configuration (equation 11). Similar results have been obtained for a-lithiated amines and carbamate protected amines " . As a rule, dipole stabilization of the organolithium compounds in general also enhances the configurational stability of a-oxygen-substituted lithium carbenoids. 

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