Dioxaspiro compounds

An amide oxygen also acts as a nucleophile in the anodic oxidation of RC0N(Me)C6H40R in MeOH to A-methylbenzoxazolium perchlorate. A metastable intermediate, detected by spectroscopy, may be a quinone imine derivative [38] and the reaction analogous to the anodic substitution of hydroquinone with certain nucleophiles, such as pyridine [35]. A somewhat similar reaction is found in the anodic oxidation of 4-methoxyacetic acid to a dioxaspiro compound [39]. 

Several early reports dealt with the resolution of racemic aziridine-2-carboxylic acids [72, 73], Treatment of ( )-78 (Scheme 3.25) with (-)-trans-2,3-bis(hydroxydi-phenylmethyl)-l,4-dioxaspiro[5.4]decane (79), for example, afforded the 1 1 ratio inclusion compound 80. Upon distillation, the inclusion compound 80 gave en-antiomerically pure (-)-78 in 33% yield. 

Spiroketals based upon such structures as l,7-dioxaspiro[5.5]undecane (18), occur frequently in natural products. Accordingly, an extensive amount of literature relates to the isolation and total synthesis of this type of compound. This literature was reviewed104 in 1989. The authors of Ref. 104 listed three factors that influence conformational preferences in these systems. They are (7) steric influences, (2) anomeric and related effects, and (3) intramolecular hydrogen bonding and other chelation effects. 

The first precise evaluation (2A, 25) of both the anomeric and the exo-anomeric effects was obtained by studying 1,7-dioxaspiro[5.5]undecane (9) (Fig. 2). With this system, conformational analysis by low temperature nmr spectroscopy was possible because each conformational change involves a chair inversion which has a relatively high energy barrier. The steric effect could also be easily evaluated, and by adding appropriate alkyl substituents, it was theoretically possible to isolate isomeric compounds which would exist in different conformations. 

Photoirradiation of inclusion crystals of 3-oxo-2-cyclohexanecarboxamide derivatives (69b-69d) with the optically active host compound 12b as a water suspension for 4 hr gave optically almost pure 2-aza-l, 5-dioxaspiro[3,5]nonane derivatives (70b-70d) [38], Optically pure 70b and 70c were prepared by the... 

Some of the first, and most versatile hosts are compounds 3a-c, which can be prepared from optically active tartaric acid. It has been found that they work as chiral selectors in solution [17], and in a powdered state [18], In the crystal structure of the free host compound (R,R)-(—)-fra s-bis(hydroxydiphenylmethyl)-l, 4-dioxaspiro[4.5]decane (3c), only one hydroxyl group is intramolecularly hydrogen bonded (Figure 1). As long as no suitable guest molecules are present, the other OH-group remains unbonded in both media. 

Optically active 19a was previously obtained by inclusion complexation with N -benzylcinchon idi um chloride 21 [36], Compound 21 was also a very efficient resolving agent for rac-17 [37], Crystal structure analysis of a (1 1) complex of 21 and selectively included (+)-17 showed that the molecular aggregate was associated by formation of a Cl HO hydrogen bond. Racemic compound 20 could be efficiently resolved only by complexation with (R,R)-(—)-trans-2,3-bis(hydroxydiphenylmethyl)-l,4-dioxaspiro[4.4]nonane 3b. A crude inclusion complex of 1 1 stoichiometry of 3b was formed selectively with (+)-20 in a 2 1 mixture of dibutyl ether/hexane. One recrystallization from the above combination of solvents gave a 34 % yield of the pure complex. Optically active (+)-20 was obtained by dissolving the complex in 10% NaOH, followed by acidification with HC1 and then recrystallization. The optical purity determined by HPLC (Chiralpack As) was >99.9 %. As far as we know, this is the only report of the resolution of 4,4 -dihydroxybiphenyl derivatives. Conversely, an inclusion... 

Adkins and co-workers found that hydrogenation of 3-(2-furyl)acrolein over nickel catalysts was accompanied by the formation of l,6-dioxaspiro[4.4]nonane (54) (eq. 12.108). The amount of the spiro compound 54 formed was greater over Ni-ki-... 

Compounds 650, DHFs substituted by a phenylsulfonyl group at the -position, have been lithiated with n-BuLi in THF at —78 °C to provide intermediates 651. They were allowed to react with different electrophiles in good yields leading to compounds 652, and with y-lactones 654 they gave dioxaspiro[4,5]decanes 653 as a mixture of diastereomers951,952 (Scheme 170). 

Even more rare are photocycloadditions involving carbonyl compounds to allenes. Arnold has found that acetone and tetramethylallene can be irradiated to form a mixture of 2-alkylideneoxetane and 1,3- and l,6-dioxaspiro[3,3]heptane products (107 108 109 = 8 31 27), all resulting from initial attack of the carbonyl n,ir state on the central carbon linkage. Hammond subsequently repented a study in which alkylideneoxetane derivatives (111) were photoisomerized to cyclobutanes (110). 

Dimethyl-4,8-dioxaspiro[2.5]oct-l-ene is a synthetically useful precursor for cyclopropenones because of its stability and ready availability. The sodium derivative 1 of the cyclopropenone acetal in liquid ammonia reacted with alkyl halides giving alkyl-substituted cyclopropenone acetals 3. The lithiated cyclopropenone acetal 4 was generated by treating the cyclopropenone acetal with one equivalent of butyllithium in tetrahydrofuran. Reaction of the lithium carbanion 4 with alkyl halides proceeded cleanly in the presence of two equivalents of hexamethylphosphoric triamide (Table 1, entries 1-4). The lithium compound underwent nucleophilic addition to carbonyl compounds smoothly at — 70 C giving hydroxymethyl derivatives 5 (Table 1, entries 5-10). 

Three long carbon-chain compounds, symbiospirols A (228), B (229), and C (230), were isolated from the culture of Symbiodinium sp., which was isolated from the marine acoel flatworm Amphiscolops sp. collected at Sesoko Island, Okinawa. Their planar structures and partial relative stereochemistries were elucidated based on NMR spectra and a degradation reaction. Symbiospirols consist of a Cgy linear chain with a A/ -dihydroxy ketone moiety, eight hydroxy groups, one tetrahydropyran ring, and two l,6-dioxaspiro[4,4]no-... 

We have discussed above the conformational profile of l,7-dioxaspiro[5.5]un-decane skeleton. There are examples of 1,6-dioxaspiro[4.5]decane skeleton as well, a skeleton that has been encountered in products of natural origin including the ionophores. Cottier et al. [25] have prepared several derivatives of 1,6-dioxaspiro [4.5]decane and shown that 175 exits as the conformer 175a in preference to 175b. These authors have also reported that the compound 176 exists in the conformation as shown, each ring oxygen having an electron pair orbital antiperiplanar to a polar... 

Substituted 2-alkoxycarbonyleyclohexanones are reduced in an even more diastereoselective manner than the 4-unsubstituted compounds. For example, the l,4-dioxaspiro[4.5]decan-8-ol derivative is prepared in high enantioselectivity with baker s yeast89 157 162. 

Rearrangements of oxaspiro compounds such as l,5-dioxaspiro-(2,6) octane and... 

Spiroketals.- The discovery that this class of compounds includes insect pheromones has stimulated extensive synthetic effort. A variety of 1,6-dioxaspiro[4.4]nonanesand 1, 6-dioxaspiro[4.5]dec-anes have been prepared by reaction of lithium salts of protected alkynols with equimolar amounts of lactones followed by hydrogena tion and acid-catalysed deprotection and cyclisation (Scheme 16). 

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