Dehydrogenations of pyrans

The dehydrogenation of 4//-pyrans 172b236 and 205b with molecular oxygen245 gave the products shown in Eq. (23)... 

The cycloaddition of l,3,4-oxadiazin-6-ones 97 (R =Ph, Pr R = Ar, C02Me) to cyclopentadiene in the presence of TFA leads to the formation of regioisomeric dihydro-a-pyrones 106 and 107 <1998CC2387>. The dehydrogenation of 106 and 107 with dichlorodicyanoquinone (DDQ) affords the a-pyrones 108 and 109. The latter are converted to cyclopenta[f]pyrans 110 with diisobutylaluminium hydride (DIBAL-H) (Scheme 13). 

Hydroqulnollnes. Pyrans formed by reactions of a,P-unsaturated aldehydes with 1-ethoxycyclohexene and treated with hydroxjiamine are converted ia good yield to 5,6,7,8-tetrahydroquiQolines (117). These compounds can be dehydrogenated to the corresponding quiaolines. The parent reduced product has been prepared by heating O-aHylcyclohexanone oxime (118). 

Dihydropyrans may be transformed to pyrans by dehydrogenation, dehydration, elimination of an alcohol or a carboxylic acid molecule, as well as by dehydrochlorination. 

The indirect dehydrogenation to pyranones has received rather more attention. The allylic bromination of 5,6-dihydropyran-2-one by NBS, followed by the elimination of hydrogen bromide, is described in detail and offers the attractions of mild conditions and easy isolation of the product (770S(56)49). A similar approach was used to synthesize the steroidal pyran-2-ones from the fully saturated lactone (354), with a combination of dehydrogenation and dehydrobromination to achieve oxidation (64MI22400). 

In an open vessel, y-tropolone allyl ether (632) predominantly gives allyltropolone 633 (and, by dehydrogenation, traces of 634 and 635) 633, however, affords 634 and 635 as the main products (Scheme 171). Pyran 634 suffers autoxidation (Section IV,A,4,a). On oxidation by CAN, y-tropolone and allyl derivative 633 dimerize to ditroponofurans 637 and 635, respectively. 

In an interesting new synthesis of a bufadienolide from cholanic acid (pregnane derivatives have been used previously), Sarel et al.1 obtained as the penultimate product a /3,-y-unsaturated 8-lactone (1), which required dehydrogenation to the desired a-pyrane (2). The lactone (1) was found to be relatively inert to DDQ in... 

Heating a 3-(2-hydroxyphenyl)propionate ester in diphenyl ether with palladium-charcoal induces a combined cyclization and dehydrogenation [3437], Simultaneous de-O-benzylation and cyclization of a 2-(benzyloxy)acrylic acid by heating with acetyl chloride containing phenyltrimethylammonium iodide gives good yields of a fused pyran-2-one [3836]. In contrast, an o-methoxy-benzylidenemalonic acid (as its potassium salt) cyclizes in the cold when treated with trifluoroacetic acid-trifluoroacetic anhydride [3938]. 

A reported preparation of 2-amino-3-cyano-4-phenyl-6-(2-thiazolyl)-4//-pyran from PhC(Me)=C(CN)2 and 2-thienylcarbaldehyde [87CI(L)60] had to be conditioned by an additional dehydrogenation process, however. 

Pyrans. Nucleophilic substitution of chloroazulene 207 (Scheme 48) with cyanoacetate and subsequent reaction with DEX3 yields pen-fused pyran 208, presumably through dehydrogenation, intramolecular cyclization, and aromatization (97M11). 

Polysubstituted 2E/-pyran-2-ones are available through rhodium(III)-medi-ated decarboxylative and dehydrogenative coupling reactions of maleic acid derivatives with alkynes, in moderate to excellent yields (Scheme 45) (13JOC11427). 

Recently such type of transformation was used for the scalable process to the GSK3p Inhibitor AZD8926 422 (Scheme 75). The process include a lithiation of l-(pyran-4-yl)-2-trifluoromethyl-imidazole 418, a Ziegler-type couphng of hthiated 419 with commercially available 2-chloro-5-fluoropyrimidine 362 via 1,2-addition over the 3,4-C-N bond and a copper-catalyzed dehydrogenative aromatization... 

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