Homer-Emmons route

5 Vinylic tellurides via olefination reactions 3.16.5.1 Homer-Emmons route 

Preparation of vinyl tellurides. To a mixture of NaH (1 mmol) (80% suspension in oil) and (phenyltelluromethyl)-phosphonate (1 mmol) in THF (5 mL) at reflux under Nj, aldehydes (1 mmol) were added dropwise. Following 3 h at reflux, the solution was cooled to room temperature. Then, saturated aqueous NH4CI was added and the mixture was extracted with diethyl ether. The organic extract was dried (MgS04) and evaporated to give vinyl tellurides, which were purified by column chromatography on silica gel with ethyl acetate/hexane (1 20) or by preparative TLC, 

These olefination reactions are not stereoselective, giving mixtures of Zand E isomers.  

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Babler and Schlidt [86] described a route to a versatile C15 phosphonate, used for a stereoselective synthesis of all E retinoic acid and p-carotene. Base-catalyzed isomerization of the vinyl-phosphonate afforded the corresponding allyl-phosphonate as the sole product. Homer-Emmons olefination with ethyl 3-methyl-4-oxo-2-butenoate concluded the facile synthesis of all E ethyl retinoate. The C15 phosphonate was synthesized starting from the epoxide of P-ionone. Subsequent isomerization with MgBr2, afforded the C14 aldehyde in 93%... 

Several variants of the Wittig olefination reaction have been adapted to solid phase (Fig. 8). Williard et al. [43] prepared a series of stilbenes using the Homer-Emmons reaction on resin-bound aldehydes. A route to either substituted or unsubstituted unsatu-... 

The remaining section highlights various other methods of generating piperidine cores. The scheme below depicts a simple route to piperidines heterocycles, such as 196, via an intramolecular Homer-Emmons cyclization of phosphonate 197 <06JA12743>. 

An elegant route to pyrazoles, involves forming a ring closure precursor by Homer-Emmons condensation of a tosylhydrazone-phosphonate with an aldehyde, which becomes the 5-substituent intramolecular Michael addition and then loss of toluenesulfinate as the final aromatising step, completes the sequence. ... 

Other commonly used synthetic routes to alkenes are also affected by crown ethers. The Wittig (80TL4831), Wittig-Homer and Wadsworth-Emmons (8 IS 117) reactions all give pure trans-alkene products in higher yields in the presence of crown ethers. 

In 1992 Toyokuni synthesized 5a-carba-a-D-fucopyranose 138 (Scheme 22) by a straightforward route involving an intramolecular Emmons-Homer-Wadsworth olefination of dioxophosphonate 136, readily available from L-fucose 135 [30]. The intramolecular olefination of 136 proceeded easily to give inosose derivative 137 which, after... 

An important application of the Reformatsky reaction is the conversion of P-hydroxy esters to a, P-unsaturated esters. Acid-catalyzed dehydration usually leads to a mixture of a, P- and P, y-unsaturated esters. However, conversion of the initially formed p-hydroxy esters to their corresponding acetates by treatment with acetyl chloride, followed by base-catalyzed dehydration with NaOEt, produces conjugated esters in high purity. This sequence of reactions provides an alternative route to the Homer-Wads worth-Emmons olefmation of ketones (see Chapter 8). 

Emmons reaction (Scheme 26). ° Horner-Wadsworth-Emmons reactions also feature in new routes to (diphenylphosphono)acetic acid esters and alkenes. The latter involve combining the Homer-Wadsworth-Emmons procedure with a Heck coupling reaction for the synthesis of tri-substituted alkenes. 

Subsequently, the nucleophilic chlorination of oc-hydroxyphosphonates has become one of the most important routes for the synthesis of a-chlorophosphonates (Scheme 3.15). A wide variety of chlorinating agents has been employed, some of which are presented in Table 3.4. Two couples, CCiyPPhj and POClj/PhNEtz, seem to give the best results, with the latter being more easily removed from the reaction mixture. The a-chlorophosphonates are important reagents for the preparation of chloroalkenes and alkynes, which are obtained after Homer-Wadsworth-Emmons reactions with carbonyl compounds. 

Tsai, H,-J, Thenappan, A., and Burton, D.J., A novel intramolecular Homer-Wadsworth-Emmons reaction, A simple and general route to a-fluoro-a,P-unsaturated diesters, J. Org. Chem., 59, 7085, 1994. 

The ether derivatives 0,0,0-trimethylkorupensamine A (248) and B have both been synthesised by a route which commenced with a lengthy sequence to the biaryl 249 from 3,5-dimethylanisole (ref. 95) (Scheme 32). Reduction of 249 with LiAlHa and oxidation gave aldehyde 250 which upon Wadsworth-Emmons-Homer extension, reduction and Sharpless asymmetric epoxidation provided epoxide 251 and the corresponding atropisomer in almost equal amounts which were separated by silica gel chromatography. The derived alcohol 252, obtained by mesylation of 251 and in situ reduction, was then converted into the acetamide 253 by displacement with azide under Mitsunobu conditions followed by reduction and acetylation. Ring closure followed by stereoselective reduction then yielded 0,0,0-trimethylkorupensamine A (248). The synthesis of 0,0,0-triraethylkorupensamine B was accomplished in a similar manner using the atropisomer of 251 obtained in the epoxidation step. 

An alternative route allowed the generation of the C5 chiral center by hetero-Michael addition on cx,p-unsaturated Weinreb amide 54, which in turn could derived from aldehyde 52 through crotyltitanation and homologation (Scheme 12). Thus, crotyltitanation reaction of aldehyde 52 with (/f)-4 cleanly led to the syn-anti homoallylic alcohol 53. a, i-Unsaturated Weinreb amide 54 was obtained through a classical two-step sequence involving a Homer-Wads worth-Emmons olefination. Then, reaction of 54 with benzaldehyde mediated by potassium bis(trimethylsilyl)amide (KHMDS) afforded benzyli-dene 55 in 79% yield with an excellent diastereoselectivity (dr >95 5). After reduction to aldehyde 56, the last C1-C7 subunit was obtained in 32.7% overall yield for eight steps. 

Homer-Wadsworth-Emmons reaction remained unimportant as a preparative route owing to the low reactivity of (136) (Pommer, 1960) toward phosphoryl anions. 

Starting from L-ascorbic acid, a chiral building block from nature, 2,3-isopro-pylidene-L-glyceraldehide 21 was obtained and subjected to an il-selective Homer-Wadsworth-Emmons-type reaction [38] with phosphonate 22 to give -alkene 23. Two-step manipulation of the diol unit in 23 afforded 24 which underwent y-allylic coupling to (R)-25 with 97% e.e. and 77% yield. In the last three steps, cyclic ketone (45)-4 was obtained, with approximately 65% yield. This can be converted to sertraline by one of the routes described above. 

Homer-Wadsworth-Emmons chemistry to generate an alkenylphosphonate intermediate that was reduced to generate the alkylphosphonate species. Normally, phosphonate fragments are introduced into the 5 -position using Michaelis-Arbuzov or MichaeUs-Becker chemistry however, this route is an attractive alternative since it avoided the high temperatures typically required for Michaelis-Arbuzov chemistry and it also eliminated the... 

Homer-Wadsworth-Emmons reactions encounter serious problems of reactivity, stereoselectivity, and generality when used to form tetrasubstituted olefins. Most studies on the synthesis of tetrasubstituted olefins exploit alternative routes based on carbometalation of alkynes [17-19]. However, these processes have difficulties associated with the regioselectivity of the initial carbometalation and with reactivity during the final coupling. Here we describe stereoselective s3mtheses of tetrasubstituted olefins, via the olefination of carbonyl compounds with ynolates, as well as some synthetic applications [20,21]. 

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