Lithiated allylic carbamates

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

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... 

Lithiated allyl carbamates stereochemistry of electrophilic substitution... 

Contrary to Uthiated alkyl carbamates, which hold a pyramidalized sp -hybridized carb-anionic centre and thus generally react with electrophiles under retention of configuration (see Section n.B.l), lithiated ( )-allyl carbamates 310 have a high tendency for antarafa-cial reactions, which seem to be enforced by the bulky sparteine as the lithium ligand (equation 79). Fortunately, in these reactions, the Af,Af-diisopropylcarbamoyloxy group prefers the ewdo-position to lead to the a-product 311 (inversion) and to the y-product (Z)-312 [sometimes besides small amounts of (E)-ent-312)]. 

Allyl carbamates 19 are even more versatile, and the lithio derivatives 20 of allyl carbamates are the most important class of homoenolate equivalents.17 Lithiated allyl carbamates react reliably at the y-position with aldehydes and ketones but less regioselectively with alkylating and silylating agents. O-Benzyl carbamates 21 are readily deprotonated and can be quenched with electrophiles.17 20... 

Allyltitanium reagents have been used in the homo-aldol reaction [76]. Enan-tiodivergent tuning by virtue of the titanium reagents of chiral l-oxyallyUithium substrates leads to enantiomeric homo-aldol products with excellent enantiomeric excess. Hoppe and coworkers found the first example of a chiral nonracemic allyllithium with configurative stabiHty [77]. In their work they described the lithiation of optically pure aUyl carbamates. These lithiated allylic carbamates are substrates for homo-aldol reactions. The so-derived chiral allyllithium compounds can be transmetaUated to titanium in order to facilitate a subsequent aldol reaction (Scheme 3.48) [76a]. 

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. 

N-Allyl tertiary amides 72 can be lithiated with r-BuLi and, like the secondary amides 54 and 57 they react y to nitrogen to give cis acylenamine products 74, with the intermediate organolithium adopting a structure approximating to 72.152 The stereochemistry of the reactions of lithiated allyl amides and carbamates in the presence of (-)-sparteine53 is discussed further in chapter 6. 

Enantioenriched a-carbamoyloxy allylic stannanes can be prepared by lithiation of allylic carbamates in the presence of (-)-sparteine (Eq. 42) [62]. Ilie resulting lithiated sparteine complex reacts with BuaSnLi at the a-position to afford the substitution product. The crotyl derivative of 80% ee is thus prepared. This stannane undergoes thermal addition to benzaldehyde at 160 °C to afford the anti- S) adduct of 79% ee in 79% yield. 

The deprotonations are complete within a few hours at -78 °C and afford the lithium car-benoid sparteine complexes (5)-l-(-)-3 with excellent enantioselectivities. [6-12] Whereas sparteine complexes of lithiated secondary allyl and primary alkyl carbamates are configurationally stable below -30 °C, those of primary allyl carbamates such as 4 (-)-3 are not configurationally stable even at -70 °C. It is, however, possible to use these reagents in synthesis, since the preferential crystallization of the S diastereomer in pentane/cyclohexane drives the equilibrium completely to one side. After a low-temperature transmetalation of (5 )-4-(-)-3 with an excess of tetraisopropo-xytitanium, the allylic titanium reagent (Ji)-S is obtained with inversion of configuration. The addition of various aldehydes to (R)-5 furnishes homoaldol adducts of type 6 with... 

Functionalized allyllithium compounds of type XIII are also homoenolate equivalents [122,130], but in their reaction with electrophiles sometimes it is not possible to control the regioselectivity. These compounds have been prepared mainly by either deprotonation or tin-lithium exchange. Deprotonation of (F)-cinnamyl-N,N-diisopropylcarbamate 155 with n-BuLi in the presence of (-[-sparteine in toluene gave a configurationally stable lithiated O-allyl carbamate (epi-156), which equilibrates at -50 °C to give the (R)-intermediate 156. Whereas the reaction of these compounds with Mel and MeOTs gave the /-attack, however acylation, silylation and stannylation took place at the a-position (Scheme 2.21) [131]. 

If further acidic C—H bonds in the molecule cause problems, the tin-trick can be applied. The asymmetric deprotonation of a bifunctional carbamate (39a) is accomplished at an early stage and the masked carbanionic centre carried through the synthesis as a stan-nyl group. For instance, the (S)-5-silyloxy-l-tributylstannyl-pentyl carbamate 39b (> 95% ee) was produced by the usual means and converted by standard steps via the aldehyde 78 into the allyl chloride 79 (equation 17) . Lithiodestannylation of 79 by n-BuLi proceeds faster than reductive lithiation in the allylic position to form the lithiocarbamate 80,... 

Allyl acetals,21 and carbamates,17 can be lithiated and quenched with metallic electrophiles at the a-position to provide allylmetals, for example, the allyl boronate 22.21 Allyl and benzyl esters have also been lithiated a to O.22... 

This chemistry can be very powerful, since the amide product itself offers further possibilities for functionalisation by lithiation. The synthesis of the natural product ochratoxin A (section 9.1) illustrates this point. Two successive ortholithiations of carbamate 210 are used first to introduce one amide group and then a second, by anionic ortho-Fries rearrangement. The symmetrical diamide 211 can be allylated and then cyclised in acid, with concomitant hydrolysis of the second amide and deprotection of the phenol to yield a known intermediate... 

Acyclic C-N bonds of allyl or benzyl triflamides,51 pivalamides and carbamate derivatives9 can be reductively lithiated, as can N-benzyl benzotriazoles.72... 

Deprotonation of O-alkyl carbamates may be achieved in an enantioselective manner with s-BuLi-(-)-sparteine, and the most effective of these reactions employ the oxazolidinones 411. The related compounds 412 perform similarly, but have less neat NMR spectra. Enantioselective lithiation of 413, followed by carboxylation and methylation with diazomethane, generates the protected a-hydroxy acid 414 in >95% ee.176 Many other electrophiles perform well in the quench step, but not allylic or benzylic halides, which lead to partial racemisation.177 30... 

V-Boc allylic amines are readily obtained by CuCN-mediated coupling of enol triflates with the a-lithiated carbamates. This method offers regio- and stereocontrol with respect to the double bond. However, it cannot be extended to the preparation of benzylamine derivatives. 

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