Synthesis and properties of 1,6-dioxaspiro[4.4]nonane and its derivatives (review)

Data on methods of synthesis and the chemical properties of 1,6-dioxaspiro-[4.4]nonane and its derivatives are correlated.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 9, pp. 1155–1168, September, 1986.     

Straightforward synthesis of 1,6-dioxaspiro[4.4]nonanes

Diols 2, easily prepared by a DTBB-catalysed lithiation of the dithioether 1 in the presence of different carbonyl compounds, react with ozone in dichloromethane at −78 °C leading, after treatment with thiourea at 20 °C, to the corresponding substituted 1,6-dioxaspiro[4.4]nonanes 3.     

Organoselenium mediated asymmetric cyclizations. Synthesis of enantiomerically pure 1,6-dioxaspiro[4.4]nonanes

The asymmetric cyclization of 1-hydroxyoct-7-en-4-one, promoted by camphorselenenyl tetrafluoroborate, generated from camphor diselenide and silver tetrafluoroborate in dichloromethane at room temperature, afforded a mixture of two diastereoisomeric E- and two diastereoisomeric Z-2-[(camphorseleno)methyl]-1,6-dioxaspiro[4.4]nonanes. These were separated by medium pressure liquid chromatography and then deselenenylated with triphenyltin hydride and AIBN to give enantiomerically pure 2-methyl-1,6-dioxaspiro[4.4]nonanes. The camphorseleno group was also substituted by an allyl function using allyltributyltin in the presence of AIBN.     

Synthesis of optically active 2-ethyl-1,6-dioxaspiro[4.4]nonane (chalcogran), the principal aggregation pheromone of pityogenes chalcographus (l.)1

((2R, 5RS)- and (2S, 5RS)-2-Ethyl-1,6-dioxaspiro[4.4]nonanes (chalcograns) were synthesized in a simple manner by applying the recent technique of dianion chemistry.     

Practical synthesis of enantiopure spiro[4.4]nonane C-(2'-deoxy)ribonucleosides

The levorotatory diol 7 has been sequentially monosilylated, dehydrated, and oxidized at the allylic methylene group to provide (+)-12. The enantiomeric dextrorotatory diol 7 has been directed down a different sequence of steps involving monosilylation, dehydration, hydroboration, Swern oxidation, and regioselective introduction of a conjugated double bond to generate (-)-33. The novel feature of these transformations is that two key deoxycarbospironucleoside intermediates of the proper absolute configuration have been made available from enantiomerically related precursors. Also reported is a highly practical and reliable means for the formation of novel 2'-deoxyribonucleosides of novel structural type from these spirocyclic cyclopentenones.     

Straightforward synthesis of 1,7-dioxaspiro[4.4]nonanes

The reaction of 2-chloromethyl-3-(2-methoxyethoxy)prop-1-ene with an excess of lithium powder and a catalytic amount of naphthalene (2.5%) in the presence of a carbonyl compound (E¹=R¹R²CO) in THF at −78 to 0 °C, followed by the addition of an epoxide [E²=R³R⁴C(O)CHR⁵] at 0 to 20 °C leads, after hydrolysis, to the expected methylidenic diols. These diols, in the presence of iodine and silver(I) oxide in dioxane-water, undergo double intramolecular iodoetherification to give the corresponding 1,7-dioxaspiro[4.4]nonanes, which in addition can be easily oxidised to a variety of 1,7-dioxaspiro[4.4]nonan-6-ones.     

Highly Efficient and Mild Gold (I) Catalyzed Synthesis of 3,8-Diarylidene-2,7-dioxaspiro[4.4]nonane-1,6-diones

The gold-catalyzed cyclization of 2,2-bis(3-arylprop-2-yn1-yl)malonic acid has been proposed as an efficient approach to substituted 3,8-dibenzyl-2,7-dioxaspiro[4.4]nonane-1,6-diones. The reaction proceeds smoothly in mild reaction conditions to give the desired products in quantitative yields in the presence of variously substituted starting materials. In addition, the synthesis of γ-arylidene spirobislactone bearing different substituents on the two aromatic rings has been achieved. This kind of compound could be of great interest in pharmaceutical science given the widespread presence of this scaffold in bioactive natural and synthetic products.     

Syntheses of Racemic and Optically Active 4-Hydroxy-2-hydroxymethyl-1,7-dioxaspiro[5.5]undecanes

Racemic and optically active 4-hydroxy-2-hydroxymethyl-1,7-dioxaspiro[5.5]undecanes were prepared in six steps from butane-1,2,4-triol and valerolactone with the longest linear sequence being four steps.     

A simple,efficient, two-step synthesis of symmetric 2,7-dialkyl-1,6-dioxaspiro[4.4]nonanes

A two-step synthesis of symmetric 2,7-dialkyl-1,6-dioxaspiro[4.4]nonanes has been achieved by double Michael addition of nitromethane with two moles of enones on Amberlyst A21, followed by in situ reduction with sodium borohydride, then spontaneous spiroketalization of the obtained nitrodiol, by the Nef reaction under acidic conditions, affords the title compounds in good yields.     

An entry to 1,6-dioxaspiro[4.6]undecanes and 1,7-dioxaspiro[5.6]dodecanes

Ketones 11a-c obtained by iterative alkylation of acetone N,N-dimethylhydrazone with iodides 6 and 8a,b or epoxide 9 followed by SiO₂/H₂O-induced cleavage of the hydrazone were quantitatively transformed into 1,6-dioxaspiro[4.6]undecanes 12a,c and 1,7-dioxaspiro[5.6]dodecanes 12b using Yb(OTf)₃ in CH₃CN.     

An efficient synthesis of the 1,6-dioxaspiro[4.4]nonan-2-one motif of the immunosuppressive triterpenoid Phainanoid F

We describe an efficient synthesis of the 1,6-dioxaspiro[4.4]nonan-2-one motif of the immunosuppressive triterpenoid Phainanoid F and its C4 epimer. A furan oxidative spirocyclization for constructing the spiro center was used as the key step. Other important reactions involved Sharpless asymmetric dihydroxylation, Weinreb ketone synthesis and Yamaguchi esterfication. The synthesis was achieved in 11 linear steps with 17.3% overall yield.     

2,3,7,8-Tetraazaspiro[4.4] nonane, 2,3,7,8-tetraazaspiro-[4.4] nona-2,7-diene and derivatives

Synthetic routes to the title compounds ( 4, 12 ) are described. Chiral derivatives of these, 2,7-bis(phenylcarbamoyl)-2,3,7,8-tetraazaspiro[4.4]nonane ( 7 ) and 3,8-dicarbomethoxy-2,3,7,8-tetraazaspiro[4.4]nona-1,6-diene ( 10 ) were prepared. Synthetic routes to diketo derivatives of other tetraazaspiro[4.4]nonanes were explored. 3,3-Dicarbethoxy-1-pyrazoline ( 24 ) and 3,3-dicarbethoxypyrazolidine ( 25 ) were prepared and their reactions with hydrazine examined. Proton and ¹³C nuclear magnetic resonance spectra of new compounds, including some 5-substituted 3-hydroxypyrazoles, are discussed in relation to structure.     

Catalytic transformations of 1,6-dioxaspiro[4,4]nonanes

Summary In the vapor phase over platinized charcoal at 300–320°, 2-and 3-alkyi-1,6-dioxaspiro[4.4]nonanes undergo the following transformations: isomerization of one of the tetrahydrofuran rings with formation of tetrahydrofuran oxo compounds, decarbonylation of tetrahydrofuran aldehydes, and isomerization of tetrahydrofuran homologs and tetrahydrofuran ketones to give aliphatic ketones and -diketones, respectively.     

1,6-dithia-spiro[4.4]nonadiene aus 2-thiazolin-5-thionen

4,4-Dimethyl-2-phenyl-2-thiazolin-5-thione ($\text{4}$) reacts with 2,3-diphenylcyclopropenone ($\text{2a}$) at 145°C and with benzonitrilio-2-propanide ($\text{6}$) at room temperature to yield the 1,6-dithia-spiro[4.4]nonadienes $\text{5}$ and $\text{7}$, respectively.