1- Acyloxy-1,3-dienes

Table 29 Additions of Dienophiles to Chiral 1 -Acyloxy-1,3-dienes (442) (Scheme 104)...

The precatalyst Cp" RuCl(COD) allowed the head-to-head oxidative dimerization of terminal alkynes and the concomitant 1,4-addition of carboxylic acid to stereoselectively afford 1-acyloxy-1,3-dienes in one step under mild conditions [89] (Eqs. 67,68). The first step of the reaction consists in the oxidative head-to-head alkyne coupling via the formation of a ruthenacycle intermediate that behaves as a mixed Fischer-Schrock-type biscarbene ruthenium complex, allowing protonation and nucleophilic addition of the carboxylate. 

In previous sections, several examples were shown using alkoxydienes or alkoxyalkenes. Acyloxy dienes are very useful in organic synthesis. One example is Bohlmann s synthesis of liglularone, which used acetoxy-diene 139 in a reaction with quinone 140 to give 141.1 An attractive feature of dienes that contain a vinyl... 

Inverse type hetero-Diels-Alder reactions between p-acyloxy-a-phenylthio substituted a, p-unsaturated cabonyl compounds as 1-oxa-1,3-dienes, enol ethers, a-alkoxy acrylates, and styrenes, respectively, as hetero-dienophiles result in an efficient one step synthesis of highly functionalized 3,4-dihydro-2H-pyrans (hex-4-enopyranosides). These compounds are diastereospecifically transformed into deoxy and amino-deoxy sugars such as the antibiotic ramulosin, in pyridines having a variety of electron donating substituents, in the important 3-deoxy-2-gly-culosonates, in precursors for macrolide synthesis, and in C.-aryl-glucopyranosides. 

Phthalazine-l,4-diones have been prepared by nucleophilic cleavage of polystyrene-bound phthalimides (Entry 7, Table 15.27). The reaction rate proved to be highly dependent on the solvent used, being low in EtOH but high in DCM. Using DMF as solvent, no phthalazinediones could be isolated [325]. Hexahydropyridazines have been prepared on cross-linked polystyrene in low yields by treatment of support-bound 1-acyloxy-l, 3-dienes with diimide [326]. 

Asymmetric Diels-AUer reactions The observation that simple acyloxy-boranes such as H2BOCOCH=CH2, prepared by reaction of BH3 with acrylic acid, can serve as Lewis acid catalysts for reactions of the a,P-unsaturated acids with cyclopentadiene (15, 2) has been extended to the preparation of chiral acyloxy-boranes derived from tartaric acid. The complex formulated as 3, prepared by reaction of BH3 with the monoacylated tartaric acid 2, catalyzes asymmetric Diels-Alder reactions of a,P-enals with cyclopentadiene with high enantioselectivity. The process is applicable to various dienes and aldehydes with enantioselectivities generally of 80-97 % ee. 

A better accessible chiral mediator is the (acyloxy)borane (CAB) 2-64 prepared in situ from a tartaric acid derivative and arylboronic acid at room temperature. Hetero Diels-Alder reaction of benzaldehyde and Danishefsky s diene 2-10 in the presence of 2-64 gave the corresponding pyrone after acidic work up with 52 - 95 % ee depending on R. The best results were obtained with R = 2,4,6-Me3Ph and 2,4,6-iPr3Ph. Similarly, with 2-60 the pyrone 2-61 with up to 97% ee was found [107]. 

L. Butene 1,4-Diones by Photolysis of 4-Acyloxy-l-chroma-l,3-dienes 224... 

Photolysis of [(Z)-2-(acyloxy)ethenyl]carbene complexes (= 4-acyloxy-1-chroma-l,3-dienes) (CO)sCr=C(OEt)-CH=C(OCOR1)R (Z)-169 (R = C6H5, t-Bu, c-Pr R1 = C6H5, c-Pr, c-C7H7CH2, f-Bu, Me2C=CH) with UV light of >300 nm affords 2-butene 1,4-diones R CO —C(OEt)=CH — COR (E)-170 (60-68%) by a novel metal-mediated acyl migration. Compounds (Z)-171 and furans 172 are formed as minor products (Scheme 72).4g... 

Asymmetric Diels-Alder Reaction of Unsaturated Aldehydes . The boron atom of acyloxyborane is activated by the electron-withdrawing acyloxy groups, and consequently acyloxyborane derivatives are sufficiently Lewis acidic to catalyze certain reactions. Thus, asymmetric Diels-Alder reactions of a,p-enals with dienes using (1) as a Lewis acid catalyst have been developed. For example, the reaction of cyclopentadiene and methacrolein gives the adduct in 85% yield (endo exo= 11 89) and 96% ee (major exo isomer) (eq 3). Some additional examples are listed in Figure 1. The a-substituent on the dienophile increases the enantioselectivity, while p-substitution dramatically decreases the selectivity. In the case of a substrate having substituents in both a- and p-positions, high enantioselectivity is observed thus the a-substituent effect overcomes that of the p-substituent. 

An analogous acyl group transfer has been observed in acylated hydrazones of 3-hydroxybenzo [ b] thiophene-2-carboxaldehyde and 1,3-benzoyl migration and E-isomerization pathways compete on irradiation of certain 4-acyloxy-2-azabuta-1,3-dienes, the... 

Palladium-catalyzed reaction of conjugated dienes in the presence of a halide anion can be controlled to give a l-acyloxy-4-halo-2-alkene selectively under appropriate reaction conditions. The catalyst for this system is a palladium(II) salt, usually Pd(OAc)2 or Li2PdCl4. The reaction may be intermolecular or intramolecular. In most cases, it is stereoselective and results in a 1,4-cis addition to the diene. The products obtained from such reactions are useful synthetic intermediates since they have two allylic leaving groups with a large difference in reactivity (see below, under Synthetic applications ). 

Several years later Danishefsky introduced l-methoxy-3-trimethylsilyloxy-l,3-butadiene, a highly reactive diene, which upon reaction with (not activated) aldehydes catalyzed with mild Lewis acids [(Eu(fod)3] afforded cyclic a, -unsaturated ketones [19]. Another method involved reaction of l,4-di-alkoxy(acyloxy)-butadiene with an activated heterodienophile, which led to more functionalized derivatives (Schmidt) [20]. This methodology may be illustrated by the classical synthesis of the precursor of purpurosamine B (3) and higher sugar... 

Conjugated ketenes. a-Diazo-y.S-unsaturated P-ketoesters undergo rearrangement to ketenes which enter Diels-Alder reactions as dienes toward electron-rich alkenes. Substituted phenols are acquired. 3-Acyloxy-2-chloro-2-cyclohexenones are formed when 2-diazocyclohexane-l,3-diones are treated with acid chlorides in the presence of Rh COAc),. ... 

Several routes applicable to the large scale conversion of testosterone into 4,5a-dihydrotestosterone have been investigated. The method of choice appears to be via catalytic reduction of a 17-acyloxy-3,3-ethylenedioxyandrost-5-ene. Platinum-catalysed hydrogenation of 19-acetoxy, hydroxy-, or methoxy-cholestan-3-ones affords higher proportions of 3a-alcohols than does the 19-unsubstituted steroid. Tritiation of 17)S-hydroxyandrosta-l,4-dien-3-one affords testosterone having a tritium ratio of 1 3.4 (a P) at C-1 and 1 1.4 at C-2 implying that reduction must proceed, in part, by 1,4-addition. ... 

Chiral (acyloxy)borane 29, easily prepared by mixing the respective monoacylated tartaric acid and phenylboronic acid, catalyzes reactions of simple aldehydes 28 with electron-rich dienes 27 with good to excellent enantiomeric excess80. 

Esters of allenyl carbinols give 2-acyloxy-l,3-dienes on treatment with AuNTf2, which is complexed to (2, 4, 6 -triisopropyl-2-biphenyl)dicyclohexylphosphine. ... 

Oxa-1,3-dienes with acyloxy functions at the C-4 position react with enolethers at room temperature, furnishing the cycloadducts with moderate selectivities. After removal of (/ )-0-methyl mandelic acid by treatment with Me0H/K2C03 the major isomer was transformed into (-)-T-olivose. 

The hetero Diels-Alder reaction of chiral enolethers with achiral 1-oxa-l,3-dienes bearing an acyloxy function at the C-2 position in the presence of Eu(fod)3, Eu(hfc)3 or Yb(fod)3 lead to dihydropyrones with high e c o-selectivity but moderate diastereoselectivity. 

The Kharasch-Sosnovsky reaction may be carried out in the presence of caiixixylic acids to introduce the acyloxy moiety of the acid used, and may also be conduct photochemically at room temperature using UV irradiation. Peroxy acids,diacyl peroxides, and peroxyphosphates and peroxyphospho-nates are alternative oxidants. r-Butyl hydroperoxide may also be us in place of peroxy esters with broadly similar results, although formations of mixed peroxides and r-butyl ethers can dien compete with allyl ester production. 

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