Tetrahydropyran-4-one

The reactions of diazomethane with heterocycles containing a ketonic grouping in the ring do not differ, in principle, from those of alicyclic ketones (see footnotes 3 and 177) ring expansion and the formation of epoxides compete. In general, ring expansion is the more important reaction for example, tetrahydropyran-4-one (99) is converted to l-oxacycloheptan-4-one (100) (60%) and 4,4 -epoxy-4-methyltetrahydropyran (101) (23%). ... 

Scheme 2.68. Diastereoselective formation of substituted tetrahydropyran-4-ones.

Similar reactions were carried out with 4//-tetrahydropyran-4-one, l-ethoxycarbonyl-4-piperidone, 4-alkylcyclohexanones, and 1,4-dioxa-spiro[4,5]decan-8-one to give the corresponding aminomethylenemalonates (278, X = O, NCOOEt, MeCH, EtCH, (CH,0),C) (86EUP168350 87USP4647566). 

There appears to be no detailed information regarding the mass spectral behaviour of tetrahydropyran-4-ones. 

A study of the influence of the heteroatom on the 13C shifts of some l-hetera-2,6-diarylcyclohexan-4-ones includes a brief consideration of tetrahydropyran-4-ones <79JOC471>. 

Tetrahydropyran-4-ones, for example diethyl 6-methyl-4-oxotetrahydropyran-3,3-dicar-boxylate (600), are brominated at C-3 (77JCS(Pl)l647). Chromanones are readily halogenated at C-3 (see above) when they are treated with phosphorus pentachloride, the reaction does not stop at monochlorination the carbonyl group is attacked and 3,4-dichloro-2//-chromene (601) is formed, an uncommon conversion of a chromanone into a chromene (79TL3901). Chroman yields 4- and 6-bromides when treated with NBS-benzoyl peroxide. 

A multistage conversion of tetrahydropyran-4-one into 3-hydroxypyran-4-one has been described <79JCS(Pl)1806>. 

Pyran-4-ones tend to give complex mixtures on chemical reduction, but catalytic hydrogenation usually gives the tetrahydropyran-4-one or the corresponding pyran-4-ol (63CR(256)1542). The influence of solvent on the nature of the product is exemplified by the reduction of 2,6-dimethylpyran-4-one, which in ethanol affords the fully reduced pyranone,... 

The enantioselective synthesis of the C(18)-C(25) segment of lasanolide A 324 can be achieved via an oxonia-Cope-Prins cascade cyclization of a-acetoxy ether 325. The in situ reduction of the oxocarbenium ion intermediate 326 with Bu3SnH prevents the formation of a tetrahydropyran 4-one side product (Scheme 81) <20050L1589>. 

Three regioisomeric tetrahydropyranones are discussed in this section tetrahydropyran-2-one 963, tetrahydropyran-3-one 964 and tetrahydropyran-4-one 965. 

An intramolecular acyl radical cyclization of acyl selenide 1024 uses a (Z)-vinylogous sulfonate to control rotamer population, affording ry -2,6-disubstituted tetrahydropyran-4-one 1025, a key intermediate during synthesis of the tetrahydropyran unit of mucocin (Equation 399) <1997TL5249>. This methodology is also applicable to the synthesis of polycyclic ethers <1996JOC4880>. 

A highly enantio- and diastereoselective hDA reaction between substituted hexadiene 1033 and aldehydes is catalyzed by Jacobsen s chiral tridentate chromium(m)-catalyst 1034 furnishing tetrahydropyran-4-ones 1035 (Equation 401, Table 48) <1999AGE2398>. This methodology is incorporated into a stereocontrolled total synthesis of (+)-leucascandrolide A <2003AGE343> and the synthesis of the C(20)-C(32) segment of the phorboxazoles... 

JOC3757>. Dirhodium(ll) carboxamidate complexes <2004AGE2665> and dendritic titanium(rv) complexes <2003CEJ5989> are also excellent catalysts for the hDA reaction between Danishefsky s diene and aldehydes leading to enantioenriched tetrahydropyran-4-ones. 

A reaction between a-diazo ketones and a,(1-unsaturated aldehydes under rhodium(ll)-catalysis provides a route to epoxy-bridged tetrahydropyran-4-ones <2002JOC8019>. This methodology allows entry to functionalized spiro-dioxa-bridged polycyclic frameworks <2002TL3931, 2003T8117>. 

A diastereoselective synthesis of all. fy -2,3,6-trisubstitutcd tetrahydropyran-4-ones 1039 via an intramolecular Prins cyclization of enecarbamates 1038 with aldehydes is used during a formal synthesis of (+)-ratjadone (Equation 403) <2004JA12216>. Similarly, tetrahydropyran-4-ones bearing quaternary centres a-to the carbonyl are accessible via a Lewis acid-mediated Prins cyclization of silyl enol ether substrates <2004JA15662>. 

Trifluoropyruvamide 1040 can react with 4-methylpent-3-en-2-one to afford the tetrahydropyran-4-one 1041 in moderate yield (Equation 404) <2004TL5611>. 

An intramolecular [2+2] photocycloaddition of allyl ethers with dioxinones followed by a base-induced fragmentation leads to substituted tetrahydropyran-4-ones <1997TL5579>. A one-pot scandium triflate catalyzed diastereoselec-tive cyclization between aldehydes and (3-hydroxy dioxinones 1046 followed by alkoxide addition to the resulting bicycles 1047 leads to 3-carboxy-substituted tetrahydropyran-4-ones 1048 with high levels of diastereoselectivity as a mixture of keto/enol tautomers (Scheme 268, Table 49) <20050L1113>. 

Table 49 Addition of nucleophiles to intermediates 1047 producing a tautomeric mixture of tetrahydropyran-4-ones 1048 (Scheme 268)...

A ruthenium-catalyzed ring opening cross-metathesis of 8-oxabicyclo[3.2.1]oct-6-en-3-one 1049 with alkenes provides an efficient method for the preparation of substituted tetrahydropyran-4-ones 1050 (Equation 408, Table 50) <1999X8169, 20010L4275>. Similarly, ozone can be used to cleave the same ring system during the synthesis of chiral tetrahydropyran-4-ones <2006T257>. 

A copper(l)-catalyzed 1,4-addition of vinylmagnesium bromide to dihydropyran-4-one 1053 proceeds in good yield and with high diastereoselectivity to afford the tetrahydropyran-4-one 1054, a key intermediate during synthetic studies towards the pederin family of antitumour agents (Equation 411) <2000J(P1)2357>. 

Exposure of the dioxanobornane 1055 to samarium diiodide in the presence of samarium metal at low temperature leads to the formation of a mixture of the tetrahydropyran-4-one 1056 and the ring opened product 1057. Treatment of this mixture with tosic acid leads to a single tetrahydropyran-4-one product (Scheme 269) <2004OL3735>. 

Procter used the cleavage of an aryloxy substituent with Sml2 to initiate aldol-type reactions.154 For example, treatment of ketone 139 with Sml2 in the presence of cyclohexanone and tetrahydropyran-4-one resulted in efficient aldol reaction to give adducts 140 and 141, respectively (Scheme 5.98). Again, an... 

The formation of poly substituted tetrahydropyran-4-ones through a Pd-catalysed intramolecular Michael addition of (3-hydroxyenones proceeds with the retention of stereocentres in the enones. The route is simple and is particularly attractive for the synthesis of the 2,6-a ft -substituted heterocycles (Scheme 26) <06CEJ7190>. 

The enantioselective conjugate addition of tetrahydropyran-4-ones and their thio analogues to nitrostyrene is achieved using proline-based catalysts <06JA9624>, as is the asymmetric aldol reaction of these substrates with benzaldehydes (Scheme 27) <06JOC8198>. 

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