Dioxanes spirocyclic

Phenyl-[l,3]dioxane 32 has been reported to bind the 0X2 receptor with a pX of 8.3 and a pXb of 7.9, and is 600-fold selective for 0X2 over 0X1 [85,86]. JNJ-10268752 (no specific structure has been disclosed) has been described as a selective 0X2 receptor antagonist (X, 0X1 /OX2 = 18/2, 500 nM, respectively) [87]. Compounds exemplified by 33 have been reported as 0X2 receptor antagonists (IC5o = 9nM) selective versus 0X1 (IC50 = 1870 nM) [88]. Recently, open chain amide 34, sulfonamide compound 35 [89,82], and spirocyclic sulfonamide 36 [90]... 

Quantum mechanical calculations show that the silyl cation (19) has a twisted structure, and that the a-C02 group provides substantial electrostatic stabilization.58 Isotope effects for its formation reaction are also reported.58 Evidence is provided for the stabilization of incipient oxocarbenium ions by axial electronegative substituents, as in (20) the presence of the most electronegative substituent results in the fastest reaction.59 Lewis acid-promoted cleavage of spirocyclic dioxanes such as (21) involves oxonium ions, and high axial vs equatorial product selectivities are possible with the correct choice of Lewis acid and nucleophile.60 Reactions which lead to 1,3-dioxenium salts have been reviewed.61... 

Treatment of bicyclic lactone 24 with benzylamine in dioxane afforded an open chain triflate amide, which was stirred in THF in the presence of potassium carbonate to cyclizate to the spirocyclic p-lactam 25 (Scheme 9) [58]. 

In the reaction of lithiated 2-hydroxybiphenyl and 2 -hydroxy-m-terphenyl with germanium dichloride-dioxane complex and GeCLj, respectively, spirocyclic ger-mabiphenanthrene compounds (Scheme 4) and l-oxa-10-germaphenanthrene (Scheme 5) were formed11. 

DDQ. a reagent typically used to deprotect p-methoxybenzyl ethers (see section 4.3 4), has been used for the deprotection of acetals19 and thioacetals.20 The use of 0.1 -0.4 equivalents of DDQ in acetonitrile-H20 (9 1) cleaves isopropylidene groups at room temperature to 80 C without affecting p-toluenesulfonyl, benzoyl, benzyl, or acetate groups. Monosubstituted dioxolanes [Scheme 3.17]21 are more readily hydrolysed than bicyclic, spirocyclic, and disubstituted systems and 1,3-dioxanes are more labile than 1,3-dioxolanes. Removal of dithioacetals requires 2 equivalents of DDQ at 80 °C... 

The spirocyclic 5-arylmethylene-l,3-dioxane-4,6-dione derivative 21, available from (-)-l-menthone, propanedioic acid, and 4-nitrobenzaldehyde, combines with diazomethane at low temperature under nitrogen expulsion to give one cyclopropane diastereomer 22 exclusively. The latter can be converted into enantiomerically pure dimethyl (S>2-(4-nitrophenyl)-l,l-cy-clopropanedicarboxylate (23)78. 

An investigation into spiro-conjugation in dioxane systems has been carried out using UV spectroscopy. The UV spectrum of a spirocyclic orthocarbonate was compared with the spectra of two other nonspirocyclic dioxane-derived compounds <82BCJ1106>. 

On another occasion, Barbas s group developed the first organocatalytic diastereospecific and enantioselective direct asymmettic domino Knoevenagel/ Diels-Alder reactions that produce highly substituted spiro[5,5]undecane-l,5,9-triones 57 from commercially available 54, aldehydes 55, and 2,2-dimethyl-l,3-dioxane-4,6-dione 56 (Scheme 1.16) [18]. Among the catalysts screened, 5,5-dimethyl thiazolidinium-4-carboxylate (DMTC) proved to be the optimal catalyst with respect to yield, and provided 57 in 88% yield and 86% ee. Up to 93% yield and 99% ee were observed when the reaction was extended to other substrates. It is noteworthy that the product 57 was accompanied by a trace amount of the unexpected symmetric spirocyclic ketone 58. 

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