Ylide compounds ester derivation

Most studies on sulfur ylide-mediated asymmetric epoxidation have concentrated on the development of the methodology. The usefulness of this approach has been demonstrated in the synthesis of a number of biologically interesting compounds. Furaldehyde-derived epoxides can be oxidized to produce glycidic esters that are versatile intermediates in several syntheses (see Scheme 10.9) [46]. The... 

The reactions between triphenylphosphine and acetylenic esters have been used to produce a number of different ylidic species including (31), dialkyl 2-(imido-iV-yl)-3-(triphenylphosphoranylidene)butanedioates (32), the steri-cally congested ylide (33) and heterocyclic phosphonium ylides (34). Thiazolyl derivatives, such as (35) and (36) have also been prepared and utilised in the synthesis of heterocylic compounds ... 

Most iodonium ylides have low thermal stability and can be handled only at low temperature or generated and used in situ. The relatively stable and practically important iodonium ylides, the dicarbonyl derivatives PhIC(COR)2 [535,540-543] andbis(organosulfonyl)(phenyliodonium)methanides, PhIC(S02R)2 [544-547], are prepared by the reaction of (diacetoxyiodo)benzene with the appropriate dicarbonyl compound or disulfone under basic conditions. A general procedure for the synthesis of phenyliodonium ylides 397 from malonate esters 396 is based on the treatment of esters 396 with (diacetoxyiodo)benzene in dichloromethane in the presence of potassium hydroxide (Scheme 2.115) [542]. An optimized method for preparing bis(methoxycarbonyl)(phenyliodonium)methanide (399) by using reaction of dimethyl malonate... 

A study of the photochemical reactions of some ylides of compound 1 showed the expected fragmentation to give, from compound 258 for example, 3-methyl-triazolopyridine and the products 259 and 260 postulated as derived from a carhene intermediate (00MI2). Ester 261 gives a hydrazone, and ylide 262 an indolizine. Thermal reactions of ylides are in Section IV. I. 

The ylides 276 derived from compound 2 undergo ring opening on thermolysis to give 2-pyridylcyanamides (Section IV.F), and react with acetylenic esters to give pyrazolopyridines (Scheme 12) (86H(24)2563). In the addition of DMAD some intermediate dihydro derivative is obtained and dehydrogenated with chlo-ranll. An ylide of system 3 is used as a catalyst (Section IV.J)... 

No S-ylide derived product at all was obtained from the Rh2(0Ac)4-catalyzed decomposition of diazomalonic ester amide 362 rather, a compound was isolated to which the structure of the Wolff rearrangement product 363 was tentatively assigned344. The desired C/S insertion product 364 was accessible, however, by photochemical decomposition of 362. 

Formate esters behave as typical carbonyl compounds in reactions with a number of ylides, eliminating phosphine oxide and forming vinyl ethers, e.g. (33).35 Stabilized phosphoranes are able to condense with the carbonyl group of cyclic thioanhydrides (34).38 Quinoline derivatives, e.g. (35), are obtained from the condensation of dicar-boalkoxy-ylides with isocyanates.37 Benzoyl isothiocyanates and keto-phosphoranes give quantitative yields of (36), which are unreactive in Wittig reactions but can be readily oxidized by selenous acid.38 The products obtained from reactions (Scheme 9) with the triazolinedione (37) depend upon the stability of the ylide used.39... 

The second class of benzo-fused heterocycles accessible from benzofuroxans are benzimidazole oxides. In this case only one carbon from the co-reactant is incorporated in the product. With primary nitroalkanes 2-substituted l-hydroxybenzimidazole-3-oxides (46) are formed via displacement of nitrite, and / -sulfones behave similarly. The nitrile group of a-cyanoacetamides is likewise eliminated to alford 2-amide derivatives (46 R = CONRjX and the corresponding esters are formed in addition to the expected quinoxaline dioxides from acetoacetate esters. Under similar conditions secondary nitroalkyl compounds afford 2,2-disubstituted 2//-benzimidazole-1,3-dioxides (47). Benzimidazoles can also result from reaction of benzofuroxans with phosphorus ylides <86T3631>, nitrones (85H(23)1625>, and diazo compounds <75TL3577>. 

One problem in the anti-selective Michael additions of A-metalated azomethine ylides is ready epimerization after the stereoselective carbon-carbon bond formation. The use of the camphor imines of ot-amino esters should work effectively because camphor is a readily available bulky chiral ketone. With the camphor auxiliary, high asymmetric induction as well as complete inhibition of the undesired epimerization is expected. The lithium enolates derived from the camphor imines of ot-amino esters have been used by McIntosh s group for asymmetric alkylations (106-109). Their Michael additions to some a, p-unsaturated carbonyl compounds have now been examined, but no diastereoselectivity has been observed (108). It is also known that the A-pinanylidene-substituted a-amino esters function as excellent Michael donors in asymmetric Michael additions (110). Lithiation of the camphor... 

The other stereoselective synthesis/281 shown in Scheme 8, foresees conversion of Boc-L-Asp-OtBu 20 into the related (3-aldehyde 22 via the Weinreb amide 21 and its reduction with diisobutylaluminum hydride (DIBAL-H). Wittig condensation of 22 with the ylide derived from (3-carboxypropyl)triphenylphosphonium bromide using lithium hexamethyldisilaza-nide at —78 to 0°C, produces the unsaturated compound 23 which is catalytically hydrogenated to the protected L-a-aminosuberic acid derivative 24. Conversion of the co-carboxy group into the 9-fluorenylmethyl ester, followed by TFA treatment and reprotection of the M -amino group affords Boc-L-Asu(OFm)-OH (25). 

Carbonyl ylides possess versatile reactivities, among which the 1,3-dipolar cycloaddition is the most common and important reaction. The reaction sequence of ylide formation and then 1,3-dipolar cycloaddition can occur in either inter- or intramolecular manner. When the reaction occurs intermolecularly, the overall reaction is a one-pot three-eomponent process leading to oxygen-containing five-membered cyclic compounds, as demonstrated by the example shown in Scheme 8. A mixture of diazo ester 64, benzaldehyde, and dimethyl maleate, upon heating to reflux in CH2CI2 in the presence of 1 mol% rhodium(ii) perfluorobutyrate [Rh2(pfb)4], yields tetrahedrofuran derivative 65 in 49% yield as single diastereomer. " ... 

Scheme 43 shows the details of the different steps involved in the equilibrium. The nucleophilic attack of the P(III) derivative on the acetylenic bond yields a 1,3-dipole which, after a fast protonation, frees aZ ion. If the subsequent addition of this ion occurs on the P atom (reaction a), a P(V) phosphorane is formed, but the addition of Z on the ethylenic C atom (reaction b) results in the formation of an ylide. Both of these reactions occur under kinetic control and, in both cases, X is always an OR group from the initial acetylene dicarboxylic ester. When the acetylenic compound is a diketone and X is an alkyl or aryl moiety, the C=0 group is much more electrophilic and the attack by the Z ion produces an alcoholate (reaction c), a new intermediate which can cyclize on to the P+ to form a phosphorane, or attack the a-C atom to form an ylide as in Scheme 42. Hence, reactions a and c can coexist, and are strongly dependent on the nature of the trapping reagent and of the P compound, but reaction b is blocked, whatever the reagent. This is well illustrated by the reaction of the 2-methoxytetramethylphospholane 147 on diben-zoylacetylene in the presence of methanol as trapping reagent. The proportions of the vinylphosphorane 157 and spirophosphorane 158 formed (Figure 24) are 13% and 84%, respectively.

In the first attempts to use a chiral a-sulfinyi ester enolate as donor in Michael additions to a -un-saturated esters, only low selectivities were observed.185 186 Better results are obtained when the a-lithio sulfoxide (174), a chiral acyl anion equivalent, is employed. Conjugate addition of (174) to cyclopent-enone derivatives occurs with reasonably high degrees of asymmetric induction, as exemplified by the preparation of the 11-deoxy prostanoid (175 Scheme 63).187 188 Chiral oxosulfonium ylides and chiral li-thiosulfoximines can be used for the preparation of optically active cyclopropane derivatives (up to 49% ee) from a, -unsaturated carbonyl compounds.189... 

Oxidative methanolysis of azetidinone 176 followed by hydrogenolysis of compound 177 afforded /3-lactam 178, which was protected to obtain the protected amine 179. The best conditions for rearrangement of 179 were found using TFA. Conversion of compound 180 to carbacephem 183 was accomplished by ketone reduction, alcohol protection, and elimination of methanol. Synthesis of carbacephem derivative 186 has been performed by rhodium(n)-catalyzed cycliza-tion of iodonium ylide 185 <1997TL6981> (Scheme 33). The iodonium ylide 185 was easily prepared from the corresponding /3-keto ester 184 and [(diacetoxy)iodo]benzene in good yield. 

The reaction of ylides with carbodiimides usually produces linear 1 1 adducts. The adducts derived from DMSO and carbodiimides undergo a facile reaction with primary alcohols to give an aldehyde (Moffat oxidation). With phenols and carboxyhc acids, alkylation products and esters, respectively, are formed. The oxidation proceeds under mild conditions and can be applied to sensitive compounds. Primary alcohols are oxidized solely to aldehydes without the formation of even trace amounts of carboxylic acids. The carbodiimide adducts generated from DMSO or the dimethylseleniumoxide " adducts have structure 369 (X = S, Se). 

Probably the most useful modification for the deprotonation route will be the condensation of N-substituted a-amino esters or derivatives (EWG = COOR, CN, etc.) with carbonyl compounds [Eq. (11)]. The intermediate iminium salts bear a highly basic hydroxide ion as a counteranion, which deprotonates the a. hydrogen immediately after its formation. The EWG-stabilized azomethine ylides thus generated will be smoothly trapped by the added dipolarophiles since they find no other reactive reagents in the reaction mixture. 

In the process shown in Eq. (11), N-unsubstituted a-amino esters are employed instead of N-substituted derivatives. The reaction of methyl gly-cinate with carbonyl compounds produces iminium hydroxide intermediates, which are then dehydrated generating N-unsubstituted azomethine ylides 85 (86CL1271 87BCJ4067). Therefore, this method is closely related to the tautomerization route, especially to the acid-catalyzed tautomerization (Section II,C). Benzaldehyde, phenylglyoxal, 2-methylpropanal, and cyclohexanone can be used as carbonyl compounds the corresponding azomethine ylides are trapped with N-methylmaleimide in excellent yields. 

An epoxidation reaction utilizing a complex diazo compound is shown in equation (30)." The addition of diazomethane to highly electron-deficient esters has been reported to yield 2-alkoxy-2-substituted epoxides (equation 31)." The stereoselectivity of the addition of diazomethane to pentulose derivative (20) was shown to be superior to that obtained using sulfur ylides, giving ratios of 95 5 in favor of (21 equation 8). However, the yields were unstated, and the products were accompanied in most cases by significant amounts of homologous ketone. ... 

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