Diesters from alkenes

Using chromium-based oxidants 2,4-Dimethylpentane-2,4-diol chromate(VI) diester, 122 Trimethylsilyl chlorochromate, 327 Using other oxidizing agents Bis(tributyltin) oxide, 41 Hydrogen hexachloroplatinate(IV)-Copper(II) chloride, 145 4-Methoxy-2,2,6,6-tetramethyl-1 -oxopiperidinium chloride, 183 Osmium tetroxide, 222 Potassium nitrosodisulfonate, 258 Samarium(II) iodide, 270 From alkenes by addition or cleavage reactions... 

A number of linear and cyclic alkenes have been studied in this reaction. The presence of a base favoured the formation of diesters from linear alkenes, whereas cyclic alkenes gave diesters even in absence of base.519 In a further study using dienes and unsaturated alcohols, ketones and esters, the dicarboxylation reaction could quite generally be achieved in good yields.S20S21... 

The Prevost Reaction allows the synthesis of anti-diols from alkenes by the addition of iodine followed by nucleophilic displacement with benzoate in the absence of water. Hydrolysis of the intermediate diester gives the desired diol.The Woodward Modification of the Prevost Reaction gives syn-diols. 

Following the first observations by Heck that Pd(OAc)2 can substitute a hydrogen atom in ethylene by a carbomethoxy group [50], Stille and James have discovered that the [Pd - Cu] couple catalyzes the incorporation of a COOMe group arising from carbon monoxide and methanol [51]. Most of the reactions with an alkene end up with a diester or a methoxyester, copper being used in stoichiometric quantities. Cyclic alkenes give preferentially diesters (Scheme 7). 

With this revision in our original plans, both alkenes and allenes were found to undergo efficient cycloadditions to produce cyclooctenone products in a new [6+2] cycloaddition process. This novel cycloaddition has been shown to proceed efficiently with alkenes tethered with sulfonamide, ether, or geminal diester Hnkers (Tab. 13.15, see page 294). Isomerization of the olefin, a potential competing reaction in this process, is not observed. Methyl substitution of either alkene in the substrate is well tolerated, resulting in the facile construction of quaternary centers. Of mechanistic importance, in some cases cycloheptene byproducts were isolated from [6+2] cycloaddition reactions in addition to the expected cyclooctenone products (that is, entries 3 and 4). 

Ru(0)(0jR)2 (R=7,8-didehydrocholesteryl acetate and cholesteryl acetate). These esters were isolated from RuO (as RuO /aq. Na(I04)/acetone) and R, and were shown by H and NMR and mass spectrometry to be Rn(VI) diesters similar to those obtained from the alkenes R with OsO. Their isolation, despite the absence of X-ray structural studies, suggests that such diesters could be involved in reactions of RuO, as indeed they are in the corresponding reactions with OsO. In each case a pair of isomeric diesters was formed (Fig. 1.31) [323, 346]. 

Both the reactions are essentially the additions of iodine carboxylate (formed in situ) to an alkene, i.e., the reaction of an alkene with iodine and silver salt. The Prevost procedure employs iodine and silver carboxylate under dry conditions. The initially formed transiodocarboxylate (b) from a cyclic iodonium ion (a) undergoes internal displacement to a common intermediate acylium ion (c). The formation of the diester (d) with retention of configuration provides an example of neighbouring group participation. The diester on subsequent hydrolysis gives a trans-glycol. 

Recently, the intramolecular nitrile oxide-alkene cycloaddition sequence was used to prepare spiro- w(isoxazolines), which are considered useful as chiral ligands for asymmetric synthesis (321). Reaction of the dibutenyl-dioxime (164) (derived from the diester 163) with sodium hypochlorite afforded a mixture of diastereomeric isoxazolines 165-167 in 74% combined yield (Scheme 6.80) (321). It was discovered that a catalytic amount of the Cu(II) complex 165-Cu(acac)2, where acac = acetylacetonate, significantly accelerated the reaction of diisopropylzinc... 

Keto esters are obtained by the carbonylation of alkadienes via insertion of the alkene into an acylpalladium intermediate. The five-membered ring keto ester 22 is formed from l,5-hexadiene[24], Carbonylation of l,5-COD in alcohols affords the mono- and diesters 23 and 24[25]. On the other hand, bicy-clo[3.3.1]-2-nonen-9-one (25) is formed in 40% yield in THF[26], l, 5-Diphenyl-3-oxopentane (26) and l,5-diphenylpent-l-en-3-one (27) are obtained by the carbonylation of styrene. A cationic Pd-diphosphine complex is used as the catalyst[27]. 

The reaction of norbomene yields the cis exo diester (equation 66).93 This exo isomer is not obtained directly by Diels-Alder chemistry. Other cyclic alkenes such as cyclopentene yield cis diesters, but isomers are obtained as a result of (3-hydride elimination-readdition from intermediates such as (23) prior to CO insertion (equation 67). Thus the palladium walks around the ring to some extent, but always stays on the same face. The extent of rearrangement can be minimized by higher CO pressures since CO insertion becomes more competitive with (3-elimination. This rearrangement becomes a critical problem in the dicarboxylation of 1-alkenes, since a variety of diesters are formed and the reaction is not particularly useful. These reactions were carried out with catalytic amounts of palladium and stoichiometric amounts of copper chloride. 

An important and frequently observed phenomenon in alkene pyrolysis is the ready equilibration of E and Z isomers at FVP temperatures above 500 °C. The apparently contrathermodynamic conversion of the E into the Z isomer has been quantified over the range 500-900 °C for stilbene, cinnamyl alcohol and cinnamonitrile37. In the last case, the proportion of Z isomer increases to 38% at 900 °C. In certain cases the diradical implicit in the isomerization process can be trapped by an intramolecular reaction and this is exemplified by the formation of 2-phenylindane in low yield from FVP of 56 at 700 °C37. The cis cyclobutene diester 58 is assumed to be formed as an intermediate in the FVP of the bicyclic sulphone 57 at 775 °C by loss of SO2 and ethylene. Under these conditions, however, it reacts further to give equal proportions of the E diesters 59... 

Homer-Wadsworth-Emmons reactions are C=C-forming condensation reactions between the Li, Na, or K salt of a /1-koto- or an a-(alkoxycarbonyl )phosphomc acid dialkyl ester and a carbonyl compound (see Figure 4.46). These reactions furnish a,/3-unsaturated ketones or 0 ,/3-unsaturated esters, respectively, as the desired products and a phosphoric acid diester anion as a water-soluble by-product. In general, starting from aldehydes, the desired compounds are produced /ra/ov-selectively or, in the case of alkenes with trisubstituted C=C double bonds, -selectively. 

The indium hydride compound, generated in situ from sodium borohydride and a catalytic amount of indium(m) chloride, selectively reduces carbon-carbon double bonds in conjugated alkenes such as a,a-dicyano olefins, a,/3-unsaturated nitriles, cyano esters, cyanophosphonates, diesters, and ketones (Scheme 107).372 This combined reagent system in acetonitrile reduces exclusively the a,/3-carbon-carbon double bond in a,/3,7,<5-unsaturated diaryl ketones, dicarboxylic esters, cyano esters, and dicyano compounds (Scheme 108).373... 

The last stages arc shown below. The ketone is protected, and the alkene oxidized to a carbonyl group, cleaving off one of the C atoms (you will meet this reaction—ozonolysis—in Chapter 35). The diester can be cyclized by a Claisen ester condensation. The stereogenic centres in the ring are not affected by any of these reactions so a Irans ring junction must result from this reaction. >... 

The second product (21) in the reaction of the diester (equation 70) results from 1,3-addition to the aromatic ring. Such addition is the major mode of reaction for benzene/alkene photocycloadditions, but with alkynes it is less common. One of the few reported examples is the addition of diphenylacetylene to esters of trimesic acid (equation 71),... 

One possible mechanism is the following. The allenyl geminal diester 70 is expected to be susceptible to Michael-type addition of LnPd(O) species to the allenyl sp carbon, resulting in the formation of the palladacyclopropane 71. Insertion of carbon monoxide into 71 and methanolysis afford the triester 72 (Scheme 11-20). The alkene geometry of the product 72 is exclusively E. The high stereoselectivity can be rationalized by assuming that a nucleophilic attack of Pd(0) species on the allenyl sp carbon in 70 takes place from the less-hindered side of a smaller alkyl substituent (R ). Needless to say, in allene 70, the two ester groups are perpendicular to the two substituents Rl and Rg. 

Next, Danishefsky s allosamizoline synthesis will be described [143,144]. The key point of their synthetic strategy is the utilization of enzymatic optical resolution to the racemic substrate. As illustrated in O Fig. 8, there are two approaches for the enzymatic optical resolution. One is the enzymatic hydrolysis of a diester [145,146,147], and the other is the enzymatic transacylation of the meso-dk> [148,149,150] (O Fig. 8). In Danishefsky s group, the former route was chosen as the key step. Treatment of diacetate 186 with electric eel acetylcholinesterase provided the monoacetate 187, which was reported by Deardorrf et al. [147]. This work was also applied to the synthesis of PG p2a in Danishefsky s laboratory [151]. On the basis of the success of their synthesis of PG p2a, diacetate 188, which was derived from the 2-alkene-l,4-diol derivative 176, was treated with electric eel acetylcholinesterase as well. Interestingly, this treatment provided the unexpected monoacetate 189 in 95% yield, > 95% ee (O Fig. 8). 

Carboxylic acids can be converted by ancxlic decarboxylation into radicals and/or carbocations. The reaction conditions are simple an undivided beaker-type cell as reaction vessel, controlled current supplied from an inexpensive d.c. power supply and meAanol as solvent are in most cases sufficient. A scale-up is fairly easy and the yields are in general good. By the radical pathway 1,/i-diesters, -diketones, -dienes and -dihalides, chiral intermediates for synthesis, pheromones and unusual fatty acids are accessible in just a few steps. The addition of the intermediate radicals to double bonds affords additive dimers, whereby four building units, two alkyl radicals from the carboxylates and two alkenes, can be coupled in one step. Five-membered hetero- or carbo-cyclic compounds can be prepared by intramolecular addition starting from unsaturated carboxylic acids. 

When vicinal diesters are employed as electron-deficient alkenes in [34-2] cycloadditions, yields as well as product distributions are markedly dependent on the specific process parameters and procedures. Listed for comparison are the results obtained from a simple standard procedure, i.e. all reaction components are mixed in a stainless steel autoclave and heated to the... 

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