Diels chemoselective

Palladium catalyzed cycloisomerizations of 6-cn-l-ynes lead most readily to five-membered rings. Palladium binds exclusively to terminal C = C triple bonds in the presence of internal ones and induces cyclizations with high chemoselectivity. Synthetically useful bis-exocyclic 1,3-dienes have been obtained in high yields, which can, for example, be applied in Diels-Alder reactions (B.M. Trost, 1989). 

The selectivity for two-alkyne annulation can be increased by involving an intramolecular tethering of the carbene complex to both alkynes. This was accomplished by the synthesis of aryl-diynecarbene complexes 115 and 116 from the triynylcarbene complexes 113 and 114, respectively, and Danishefsky s diene in a Diels-Alder reaction [70a]. The diene adds chemoselectively to the triple bond next to the electrophilic carbene carbon. The thermally induced two-alkyne annulation of the complexes 115 and 116 was performed in benzene and yielded the steroid ring systems 117 and 118 (Scheme 51). This tandem Diels-Alder/two-alkyne annulation, which could also be applied in a one-pot procedure, offers new strategies for steroid synthesis in the class O—>ABCD. 

The combination of thionation by Lawesson s reagent [98] of oxoenamino-ketones 96 with normal electron-demand Diels-Alder reaction of conjugated aldehydes allows a variety of thiopyrans 97 to be synthesized by a regio-selective and chemoselective one-pot methodology [99] (Equation 2.28). Thionation occurred at the more electrophilic ketonic carbonyl group. O O... 

Chemoselective alkenylation in the C-3 position of N-substituted 3,5-dichloropyrazin-2(lH)-ones has been described by Van der Eycken et al. [27]. When a mixture of N-substituted 3,5-dichloropyrazin-2(lH)-one, ethyl acrylate, and NEts in DME, using Pd(OAc)2/DTPB [2-(di-f-butylphosphanyl)bi-phenyl] as a precatalyst, was irradiated for 15 min at 150 °C, the desired /1-fimctionabzed ethyl acrylates could be obtained in moderate yields (Scheme 81). When styrene was used as an alkene, a mixture of E and Z products was isolated. The type of catalyst used proved to be important to avoid competitive Diels-Alder reaction of ethyl acrylate with the hetero-diene system of 3,5-dichloro-l-benzylpyrazin-2(lH)-one. 

This is nearly a Diels-Alder adduct and removal of the extra CHg group gives a Dlels-Alder adduct (2). The reaction must be chemoselective addition of CH2N2 to one carbonyl group only of (2). This is most easily achieved from the anhydride (3). 

In order to study any chemoselectivity influences of microwave irradiation on the domino Knoevenagel/hetero-Diels-Alder process (the so-called Tietze reaction), Raghunathan and coworkers [31a] investigated the transformation of 4-hydroxy coumarins (10-85) with benzaldehydes 10-86 in EtOH to afford pyrano[2,3-c]cou-marin 10-87 and pyrano[2,3-b]chromone derivatives 10-88. Normal heating of 10-85a and 10-86a at reflux for 4h gave a 68 32 mixture of 10-87a and 10-88 in 57% yield, whereas under microwave irradiation a 97 7 mixture in 82% yield was obtained. Similar results were found using the benzo-annulated substrates 10-85b and 10-86b. 

Figure 17.3 Maleimide-modified glass slides (1) can be derivatized using two chemoselective ligation reactions to create biotin modifications. In the first step, alkyne-PEG4-cyclopentadiene linkers (2) are added to the maleimide groups using a Diels-Alder reaction. In the second reaction, an azido-PEG4-biotin compound (3) is reacted with the terminal alkyne on the slide using click chemistry to result in another cycloaddition product, a triazole ring.

An intramolecular cycloaddition also occurred with 3-ylidenepiperazine-2,5-diones such as 124 or 125, obtained by Wittig-Horner-Emmons reaction from phosphonate 121 and aldehydes 122 or 123, respectively. The products of the Diels-Alder reaction are the bridged bicyclo[2.2.2]diazaoctane rings 126 and 127 that have been found in biologically active secondary metabolite such as VM55599 and brevianamide A. The different type of structures employed in this case requires a chemoselective reaction in order to produce the expected products as single diastereoisomers after 20 days (Scheme 18) <2001JOC3984>. 

In addition, iodine snccessfnlly catalyzed the electrophilic snbstitntion reaction of indoles with aldehydes and ketones to bis(indonyl)methanes [225], the deprotection of aromatic acetates [226], esterifications [227], transesterifications [227], the chemoselective thioacetalization of carbon functions [228], the addition of mercaptans to a,P-nnsatnrated carboxylic acids [229], the imino-Diels-Alder reaction [230], the synthesis of iV-Boc protected amines [231], the preparation of alkynyl sngars from D-glycals [232], the preparation of methyl bisnlfate [233], and the synthesis of P-acetamido ketones from aromatic aldehydes, enolizable ketones or ketoesters and acetonitrile [234],... 

Diels-Alder reaction chemoselectivity Me3Si < (t-Bu)Me2Si < (t -Pr)3Si 86... 

The chemoselectivity of the thermal cyclisation of the arylideneacetylacetone derivative (12) is influenced by the choice of catalyst. Thus, with Li and Ba perchlorates, a hetero-Diels-Alder... 

A palladium-catalyzed intramolecular benzannulation of bis-enynes 1135 proceeds chemoselectively to afford dihydroisocoumarins 1136 (Equation 441) <2002JOC2653>. A reaction sequence involving ruthenium-catalyzed yne-ene cross-metathesis of a polystyrene supported undecynoic acid ester followed by a Diels-Alder cycloaddition reaction with DMAD provides the basis for a combinatorial approach to dihydroisocoumarins featuring a variety of side chains at C-6 and C-8 <1999SL1879>. 

This benzene oxide may look very dubious and unstable, but benzene oxides can be made in the laboratory by ordinary chemical reactions (though not usually by the direct oxidation of benzene). We can instead start with a Diels-Alder reaction between butadiene and an alkyne. Epoxidation with a nucleophilic reagent (HO-O- from H2O2 and NaOH) occurs chemoselectively on the more electrophilic double bond—the one that is conjugated to the electron-withdrawing carbonyl group. 

Hetero-Diels-Alder reactions of other a, -clhylenic trifluoromethyl ketones provide a good alternative access to trifluoromethyl-substitutcd dihydropyrans (Tabic 7). These cycloadditions occur with inverse electron demand with electron-rich heterodienophiles such as vinyl ethers. They are performed under mild thermal conditions or at room temperature and are chemoselective and rcgioselective. but generally not stereoselective. 

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