Homoaldol reaction

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... 

Titanated allyl carbamates are reported to react regio- and stereospecifically with aldehydes [52]. An elegant and synthetically useful method based on diastereoselective and en-antioselective homoaldol reactions has been developed (Scheme 13.25) [53]. 

Scheme 13.25. Diastereoselective and enantioselective homoaldol reactions using titanated allyl carbamates.

When the protocol is applied to allylcarbamates 170, the deprotonation in the presence of (—)-sparteine does not occur with kinetic preference. Indeed, a dynamic resolntion by crystallization takes place. The epimeric allylfithinm componnds 171 and 172 are eqni-librating, whereby one of them crystallizes predominantly. Under optimized conditions, when n-butyllithium is used for the deprotonation and cyclohexane serves as a cosolvent, the preference of the diastereomer 172 leads to snbstimtion products in 90-94% gg393-395 enantioselective homoaldol reaction has been developed based on this protocol Transmetalation of the organolithium into the titaninm compound occnrring nnder inversion of the configuration (172 173) and subseqnent addition to aldehydes leads to... 

SCHEME 24. (-)-Sparteine-induced deprotonation of allyl carbamate 170. Dynamic resolution by crystallization and enantioselective homoaldol reaction... 

Homoaldol reaction with enantioenriched l-metallo-2-alkenyl... 

The most important reaction, the homoaldol reaction of the titanium derivatives, proceeds as an efficient syn-S process and will be discussed separately (see Section IV.C.5). Reactions with further electrophiles will be presented very briefly. The silylation of primary substrates 302 by different chlorotriorganosilanes proceeds with good a-selectivity and with inversion of the configuration ... 

Since enol carbamates of 4-hydroxyalkanals (or y-hydroxyalkanones) are produced by formation of the C(3)—C(4) bond, we named the process homoaldol reaction 244-246... 

Some alkenyl carbamates leading to configurationally labile lithium intermediates could be subjected to asymmetric homoaldol reaction with less efficiency (Scheme 6) these reactions have not been optimized yet Azs... 

Z)-awh-4-Hydroxy-l-aIkenyl carbamates 363, when subjected to substrate-directed, vanadyl-catalysed epoxidation , lead to diastereomerically pure epoxides of type 364 (equation 99)247,252,269 qqjggg epoxides are highly reactive in the presence of Lewis or Brpnsted acids to form -hydroxylactol ethers 366 in some cases the intermediate lactol carbamates 365 could be isolated . However, most epoxides 364 survive purification by silica gel chromatography . The asymmetric homoaldol reaction, coupled with directed epoxidation, and solvolysis rapidly leads to high stereochemical complexity. Some examples are collected in equation 99. The furanosides 368 and 370, readily available from (/f)-0-benzyl lactaldehyde via the corresponding enol carbamates 367 and 369, respectively, have been employed in a short synthesis of the key intermediates of the Kinoshita rifamycin S synthesis . 1,5-Dienyl carbamates such as 371, obtained from 2-substituted enals, provide a facile access to branched carbohydrate analogues . 

Lithium-metal exchange in the lithium-)—)-sparteine complexes 399 or 402, respectively, by diethylaluminium chloride or triisopropoxytitanium chloride proceeds with inversion providing useful reagents for enantioselective homoaldol reactions... 

In 1996, McWilliams and coworkers described a very interesting tandem asymmetric transformation whereby an asymmetric 1,2-migration from a higher-order zincate 60 was coupled with a stereoselective homoaldol reaction (equation 26)29. 

Hoppe, D. Enantiomerically enriched l-(N,N-diisopropylcarbamoyloxy) -1,3 -dimethylallyl-lithium stereochemistry of the stannylation, titanation, and the homoaldol reaction. Tetrahedron 1992, 48, 8377-8388. 

Hoppe, D. Hanko, R. Bronneke, A. Lichten-berg, F. Highly alkylated 1-oxyallyl anions from N,N-dialkylcarbamic add allyl esters y-hydroxyalkylation (homoaldol reaction). Angew. Chem. Int. Ed. 1981, 20,1024-1026. 

If aldehydes are used as the electrophiles, a kind of homoaldol reaction occurs in the presence of MesSiCl to give the protected y-hydroxyesters 67 in good yield. The zinc salt (ZnCL or Znl2), used to make 59 also acts as a Lewis acid for the reaction. 

Diastereoselective homoaldol reaction. The allylaluminum reagent (E)-2, obtained by deprotonation of (E)-l followed by transmetallation, undergoes a highly diastereoselective reaction with an aldehyde (or a ketone) to give E)-anti-3. In contrast, (Z)-2 reacts to give (E)-JV -3. ... 

HOMOALDOL REACTION Allyl-9-borabicy-clo[3.3. l]nonane. B-AIIyldiisopinocam-pheyl-borane. 2-Butenylcarbamates. Tri-n-butylcrotyltin. 

The isomeric methyl 3,6-dideoxy-3-C-methylhexofuranosides 230 and 232 (Scheme 13.71) were derived from (S )-2-benzyloxypropanal via homoaldol reactions in three steps. Addition of a-titanated ( -2-butenylcarbamate ( )-226 to (S )-2-benzyloxypropanal gives in 80% yield a 53 47 mixture of enantiomerically pure (Z)-3,4-antiadducts 227 and 228. These are separated by chromatography on silica gel. Face-selective epoxidation of 227 yields 229, the acidic methanolysis of which forms 230. Similarly, adduct 228 is converted into epoxide 231 and then into methyl furanoside 232 in high yield [128]. 

Hoppe, D, Tarara, G, Wikens, M, Jones, P G, Schmidt, D, Stezowski, J J, Enantioselective synthesis of methyl furanosides of unnatural 3,6-dideoxy-3-methylaldohexoses form lactates hy homoaldol reactions, Angew. Chem. Int. Ed. Engl., 26, 1034-1035, 1987. 

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