Enoates Diels-Alder reaction

G. Helmchen, R. Karge, J. Weetman, Asymmetric Diels-Alder Reactions with Chiral Enoates as Dienophiles, in Modem Synthetic Methods (R. Scheffold, Ed.), Vol. 4, 262, Springer, Berlin, 1986. 

Diels-Alder Reactions. (i )-Pantolactone is one of the most effective chiral auxiliaries for preparative scale Diels-Alder additions of simple enoate esters in the presence of Lewis acids (eq 1). ... 

Studies on the control of the absolute topicity of the Diels-Alder reaction started in 1961, but it is only during the last decade that substantial progress has been achieved. The development of this challenging field up to 1984 is the subject of sevend review articles. A more specialized account on chiral enoate... 

The thiophilic nature of copper can be used to activate the dienophile in Diels-Alder reactions (Sch. 45) [86], The copper forms a chelate with the enoate oxygen and sulfur in 201, accounting for the observed high facial selectivity. 

Branchadall and co-workers studied the effect of Lewis acid (AlCfO catalysis on the Diels-Alder reactions of methyl (Z)-(5)-4,5-(2,2-propylidenedioxy)pent-2-enoate (10) with cyclopentadiene, which usually exhibits a high level of syn-endo selectivity under the influence of the Lewis acid, at the B-LYP/6-31G level [16]. The most stable conformation of the complex IO-AICI3 revealed the significant difference with the structure of uncomplexed molecule, i.e., s-trans arrangement of the carbonyl group with respect to the carbon-carbon double bond (Fig. 1-3). 

In one case the reaction was conducted as a genuine Diels-Alder reaction on the silyl enol ether 45 of the a -enolate 44 to see what the result would be.9 The Diels-Alder reaction 47 with the enantiomerically pure enoate ester 46 required 160 °C and gave a 40% yield of a 1 1 mixture of diastereoisomers of 49. 

Helmchem G, Karge R, Weetman J (1986) Asymmetric Diels-Alder Reactions with Chiral Enoates as Dienophiles. In Scheffold R (ed) Modern Synthetic Methods. Springer-Verlag, Berlin Heidelberg, p 262 Dias LC (1997) J Braz Chem Soc 8 289 Oh T, ReiUy M (1994) Org Prep Proc Int 26 129 Kagan HB, Riant O (1992) Chem Rev92 1007... 

The use of a boron atom as a covalent template for intramolecularizing the Diels-Alder reaction has been relatively little investigated [20-22]. However Narasaka et al. have reported the use of a boronate template to control regio- and stereoselectivity in an IMDA reaction between anthrone 50 and methyl 4-hydroxybut-2-enoate 3 [20a]. Formation of the boronate tether was achieved by simply heating an equimolar mixture of phenylboronic acid with the diene and dienophile at reflux in pyridine with azeotropic removal of water. After 5 h, a single cycloadduct 51 was obtained in 81% yield. The tether was readily removed oxidatively affording the corresponding diol 52 in excellent yield (Scheme 10-19). 

There are many other enantiomericaUy pure boron-based Lewis acid catalysts used in the Diels-Alder reaction, Amongst these the dichloroborane (8.40) used by Hawkins is noteworthy because the substrates used were enoate esters, such as methyl acrylate (8.41) ° a, 3-unsaturated ketones and acid chlorides such as (8.42) rather than the enals generally tested in Diels-Alder reactions. 

In the mid-1980s, Hoffman and co-workers described a simple synthesis of racemic mikanecic acid via in situ Diels-Alder dimerization of the diene generated from t-butyl 2-bromomethylbut-2-enoate. " The first example of a Diels-Alder reaction of a MBH adduct was the dimerization of 2-hydroxy-alkyle-nones" and the previously mentioned addition to anthracene. The appKcation of the MBH adducts as hetero dienes or precursors of dienes, and dienophiles for the Diels-Alder cycloaddition reactions was then initiated and expanded by the group of Hoffman. In a series of reports, Hofftnan and co-workers have described the in situ Diels-Alder dimerization of various dienes (157), generated via stereoselective dehydration with MsCl-DABCO-DMAP of the corresponding MBH adducts The elimination of water from MBH adducts always resulted... 

Gebbink et al. reported that the immobilized Cu(II)-chiral bis(oxazoUne) complexes were employed as new heterogeneous catalysts for the hetero-Diels-Alder reactions (O Leary et al 2004). The hetero-Diels-Alder cycloaddition between ethyl ( )-2-oxopent-3-enoate and ethyl vinyl ether could be facilitated by these immobilized catalysts, but only up to 42% ee, with a low conversion of 25% being obtained (Scheme 4.23). 

The carbonylative cyclization of 2-iodophenols with norbornadiene or norbornene was also carried out. In 1989, Catellani s group studied the annulation of 2-iodophenol with norbornadiene to coumarin (Scheme 3.11a). ° In this method, the elimination of cyclopentadiene via retro-Diels-Alder reaction was involved in the formation of the terminal product. Fiaud and co-workers reported the palladium-catalyzed carbonylative cyclization of 2-iodophenol with norbornene in 1997 (Scheme 3.11b). They reported that the selectivity for the production of the two regioisomers can be controlled. Catellani and co-workers studied the intramolecular cyclization of ort/zo-iodophenyl 3-butenoate to 4-methylcoumarin with a palladium catalyst. 85% of 4-methylcoumarin was produced in the presence of benzonitrile and carbon monoxide, which is compulsory (Scheme 3.12a). Silva, Costa and their co-workers reported a tandem process for the synthesis of coumarins from 2-iodophenols and enoates with the assistance of a palladium catalyst (Scheme 3.12b). The general scope of this Heck-lactonization involves E- and Z-enoates as substrates. It was shown that this reaction is sensitive to steric hindrance around the double bound in... 

One of the most useful features of the Diels-Alder reaction is that it is stereospecific, meaning that a single product stereoisomer is formed (Section 8.9). Furthermore, the stereochemistry of the reactant is maintained. If we carry out the cycloaddition with a cis dienophile, such as methyl cis-but-2-enoate, only the cis-substituted cyclohexene product is formed. With methyl frans-but-2-enoate, only the trans-substituted cyclohexene product is formed. 

The high stereoselectivity of these reactions simply reflects the fact that the C(8) methyl group prefers to occupy a pseudoequatorial position in each TS independent of the medium. Note that the classical Diels-Alder reaction between the enoate C(2)-C(3) dienophile and the remaining C(10)-C(13) diene (which is not observed) would result in the formation of an eight-membered ring incorporating a trans-olefin. 

Wang and coworkers developed an intriguing strategy for the inverse-electron-demand Diels-Alder reaction to afford spiro compounds [51]. The reaction of a cyclopentyl keto-enolate salt 89 with A-tosyl-2-methylenebut-3-enoate 88 was catalyzed by the bifunctional primary amine-thiourea catalyst derived from rosin XXII to afford the spirocycles 90 in excellent yields (85-99%), excellent diastereoselec-tivities (up to >20 1 dr), and excellent enantioselectivities (90-99%, Scheme 10.31). 

Synthesis of dicyano-2-methylene-but-3-enoates as novel dienes for aU-carbon-based asymmetric inverse-electron-demand Diels-Alder reactions with aldehydes was also developed [37]. 

New additions to the hetero Diels-Alder (hDA) approach to dihydropyrans include the reaction between enol ethers and 3-aryl-2-cyanoprop-2-enoates that under high pressure yields substituted 3,4-dihydro-2W-pyrans with high endo- and complete regio- selectivity. The products can be transformed into a wide variety of other compounds <02EJO3126>. 

Intramolecular [3-I-2]-cycloaddition reactions have also been performed using alkyne moieties as reactants. An early example of this methodology is the high-yield formation of 27 from alkyne 26. As in the case of the (Z)-3-benzyloxybut-2-enoate derivatives (vide supra), the presence of the 3-siloxy group is essential for the reaction to proceed. A diastereomeric mixture of 26 leads to the formation of the two diastereomeric bicyclic adducts 27 in a combined yield of 88%. ° Interestingly, albeit with only 60 /o conversion after 100 hours, the same products are also formed at room temperature under the influence of ultrasound and 6 mol /o of tetrakis(triphenylphosphane)palladium(0) as catalyst. In a purely thermal reaction in the absence of a metal catalyst, a totally different reaction, presumably involving a Diels —Alder type addition of the alkyne to a vinylbenzene moiety, takes place. ... 

Pachybasin, 2-methyl-4-hydroxyanthra-9,10-quinone has been obtained in 73% yield by Diels-Alder addition from 2-bromonaphthoquinone and the vinylketene mixed acetal, 1-trimethylsiloxy-1-methoxy-3-methylbuta-1,3-diene, by reaction in dichloromethane containing potassium carbonate, heating with sodium acetate and finally aromatisation of the crude product by refluxing in ethanol The diene was accessible from methyl senecioate (methyl 3-methylbut-2-enoate) by treatment with lithium diisopropylamide and trimethylchlorosilane (ref.25). 

An Indian group report that the thermal cyclization of methyl a-eleo-stearate (18 3 9cll/13/) and of its 18-hydroxy-derivative (kamlolenate) in the presence of sulphur furnishes disubstituted cyclohexadienes [such as (29)], with the double-bond positions varying somewhat with the reaction temperature. The diene (29) obtained at 160 °C undergoes an interesting reaction with dimethyl but-2-ynedioate (acetylenedicarboxylic ester) since the Diels-Alder adduct is decomposed to methyl phthalate and methyl tetradec-cw-9-enoate. The results are summarized in Scheme 4. 

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