Wittig-Homer reactions selectivity

In the other approach, again harmalane (150) was treated with methyl 2-(di-ethylphosphono)acrylate (174), resulting in iminophosphonate 175. By its sodium borohydride reduction and subsequent lactonization, the amidophospho-nate 176 has been obtained, Wittig-Homer reaction of 176 with acetaldehyde followed by selective reduction of the carbonyl group of the enamide function supplied ( )-deplancheine in good yield (116). 

WUtig-Horner reaction. High syn-selectivity is possible in the Wittig-Homer reaction of aldehydes with alkyl diphenylphosphonates (10, 2), formulated in equation (I). 

Z)-OL, -Unsaturated esters,l Wittig-Homer reactions generally show a preference for formation of (E)-alkenes. Thus (E)-a,p-unsaturated esters are obtained preferentially on reaction of aldehydes with trimethyl phosphonoacetate under usual conditions (potassium f-butoxide). Use of a highly dissociated base can favor (Z)-selectivity. The most effective base for this purpose is potassium hexamethyldisilazide, KN[Si(CH3)3]2, in combination with 18-crown-6, although even potassium carbonate with the crown ether is fairly effective. The (Z)-selectivity can be further enhanced by use of 1 as the phos-phonoester. Under these conditions, (Z)-unsaturated esters can be prepared from aliphatic and aromatic aldehydes with Z/E ratios as high as 50 1. The method is also useful for transformation of unsaturated aldehydes to (E,Z)-dienoates and (E,E,Z)-trienoates. 

Photochemistry and mobility of the stilbenoid dendrimers [all-( )-l,3,5-tris[2-(3,4,5-tridodecyloxyphenyl)ethenyl]benzene] and [all-( )-l,3,5-tris(2- 3,5-bis[2-(3,4,5-trido-decyloxyphenyl)ethenyl]phenyl ethenyl)benzene] in their neat phases were synthesized and investigated [129]. Selectively deuterated, dodecyloxy-substituted stilbenoid dendrimers of the first and second generations (Figure 1.21) were synthesized by a convergent synthesis, using the Wittig-Homer reaction. Molecules deuterated at the... 

Wittig-Horaer reaction to give vitamin D2. The unique feature of this synthesis is the synthesis and preservation of the Z-geometry of C-5,6 double bond while the final step of the Wittig-Homer reaction allows the selective formation of J -geometry for the C-7,8 olefin. 

No reaction occurs without sonication. Quantitative yields are obtained after only a 5-min exposure to ultrasoimd. The catalyst contains reducing and basic sites. Selective poisoning of the former by m-dinitrobenzene demonstrated the high probability of a SET mechanism. The same group also concluded on the preferential SET mechanisms for Michael, Wittig-Homer, and Claisen-Schmidt condensations in the presence of the same catalyst. 

At the outset we realized that to draw rigorous conclusions we needed to examine both E- and Z-enol ethers. Therefore, our synthesis was devised to provide both isomers in quantity. The key reaction selected to generate the enol ethers was the Warren modification 1 7 of the Homer-Wittig reaction. The advantages of this method are 1) the availability of the various alkoxymethylphosphine... 

Methods for the synthesis of retinoids (Acitretin, Etretinate, Isotretinoin, Tretinoin and Alitretinoin) derived from the tetraenoic acid platform via Wittig-Homer-Emmons reactions and photochemistry are described. Chemistry enq>loyed for synthesis of the more novel aryl/heteroaryl receptor selective retinoids (Bexarotene, Differin and Zorac ) platforms is also reported. 

The major approach for synthesis of retinoids of the tetraenoic acids involves the Wittig-Homer-Emmons reaction. The photochemical reaction has also proved viable and conditions to perform this reaction on commercial scale have been identified. Identification of receptor selective retinoids expanded the chemistry of file retinoids to aryl (Bexarotene, Adapalene) and heteroaryl (Tazarotene) platforms. These analogs are prepared rapidly and efficiently and this chemistry should facilitate both the SAR and commercial development of more novel and selective members of the retinoid class. 

Synthetic analogues have been prepared as exemplified in Scheme 14 [95]. A first Wittig-Homer olefination of aldehyde 107, followed by acidic treatment, generates cyclohexenone 108. Chemo- and stereoselective reduction of the latter with 9-BBN followed by sy -selective epoxidation of the allylic alcohol (lateral hydroxyl group control) by w-chloroperbenzoic acid gives 109. Selective tosylation of its secondary alcohol moiety (steric hindrance makes the tosylation of the tertiary alcoholic moiety difficult) and subsequent deprotonation of the tertiary alcohol with NaH provide an alcoholate that undergoes an intramolecular displacement reaction. 

The results of the olefination reactions obtained with the Reformatsky approach are similar to those of the Wittig-Homer and the Homer-Wadsworth-Emmons methodologies. But in contrast to these, the position of the newly formed double bond in the Reformatsky approach is not always certain, as exemplified in the synthesis of the kappa opiate agonist [ C]PD-17,30212461. where a mixture of double bond isomers 242 and 243 was obtained. In this case, fortunately, the lack of selectivity was unimportant because both were... 

Preparation of Derivatives. Enoate derivatives were prepared by Homer-Wittig reactions between aldehydes and the ethyl phos-phonate derived from the chloroacetyl ester of (3) in high E) selectivity (97 3). Ester derivatives were obtained by treating alcohol (3) with the corresponding carboxylic acid chloride. ... 

The Wittig and Homer processes can be combined in a cyclic process to form ( -dienes (249 Scheme 35). The initial Wittig process proceeded in 63% yield with 68 32 to (Z)-selectivity. Deprotonation of the phosphine oxide (248) and reaction with benzddehyde gave exclusively the erythro isomer in 82% yield. The phosphine oxide was eliminated with NaH in DMF to give the ( .Z)-1,6-diene in an isomer ratio of 92 8 with the ( , )-diene. 

Rehwinkel, H., Skupsch, J., and Vorbrtiggen, H., E- or Z-selective Homer-Wittig reactions of suhsti-tuted bicyclo[3.3.0]octane-3-ones with chiral phosphonoacetates. Tetrahedron Lett., 29, 1775, 1988. Tiillis, J.S., Vares, L., Kann, N., Norrby, P.-O., and Rein, T., Reagent control of geometric selectivity and enantiotopic group preference in asymmetric Horner-Wadsworth-Emmons reactions with meso-dialdehydes, J. Org. Chem., 63, 8284, 1998. 

One of the limitations of the Warren s adaptation of Homer-Wittig olefina-tion, the failure of the (Z)-selective route when the alkene has a branched chain substituent, has now been overcome. Reduction of the p-ketophosphonates carrying a-branches, e.g. (112) and (113), with sodium borohydride and cerium chloride gives excellent a / -stereoselectivity and hence (Z)-alkene on base-induced elimination. Enantioselective synthesis of both jy -(115) and anti- ll) P-hydroxy-phosphine oxides has been achieved with up to 90% e.e. through two separate approaches. The jyn-isomer was obtained by reduction of the corresponding ketone (114), while the anti-isomer is the product of the reaction of the oxazolidine substituted aldehyde (116) with lithiated diphenylmethyl-phosphine oxide (Scheme 10). A new, highly stereoselective approach to trisubstituted alkenes has been reported. Cerium(III) chloride-promoted... 

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