Dioxaspiro

An ipso attack on the fluorine carbon position of 4-fIuorophenol at -40 °C affords 4-fluoro-4-nitrocyclohexa-2 5-dienone in addtion to 2-nitrophenol The cyclodienone slowly isomenzes to the 2-nitrophenol Although ipso nitration on 4-fluorophenyl acetate furnishes the same cyclodienone the major by-product is 4 fluoro-2,6-dinitrophenol [25] Under similar conditions, 4-fluoroanisole pnmar ily yields the 2-nitro isomer and 6% of the cyclodienone The isolated 2 nitro isomer IS postulated to form by attack of the nitromum ion ipso to the fluorine with concomitant capture of the incipient carbocation by acetic acid Loss of the elements of methyl acetate follows The nitrodienone, being the keto tautomer of the nitrophenol, aromatizes to the isolated product [26] (equation 20) Intramolecular capture of the intermediate carbocation occurs in nitration of 2-(4-fluorophenoxy)-2-methyIpropanoic acid at low temperature to give the spiro products 3 3-di-methyl-8 fluoro 8 nitro-1,4 dioxaspiro[4 5]deca 6,9 dien 2 one and the 10-nitro isomer [2d] (equation 21)... 

Total syntheses of naturally occurring molecules possessing l,7-dioxaspiro[4,4] nonane skeletons 99EJ01757. 

A solution of 12.5 g (0.088 mole) of l,4-dioxaspiro[4.5]decane (Chapter 7, Section IX) in 200 ml of anhydrous ether is added to the stirred mixture at a rate so as to maintain a gentle reflux. (Cooling in an ice bath is advisable.) The reaction mixture is then refluxed for 3 hours on a steam bath. Excess hydride is carefully destroyed by the dropwise addition of water (1-2 ml) to the ice-cooled vessel until hydrogen is no longer evolved. Sulfuric acid (100 ml of 10% solution) is now added followed by 40 ml of water, resulting in the formation of two clear layers. The ether layer is separated and the aqueous layer extracted with three 20-ml portions of ether. The combined ethereal extracts are washed with saturated sodium bicarbonate solution followed by saturated sodium chloride solution. The ethereal solution is dried over anhydrous potassium carbonate (20-24 hours), filtered, and concentrated by distillation at atmospheric pressure. The residue is distilled under reduced pressure affording 2-cyclohexyloxy-ethanol as a colorless liquid, bp 96-98°/ 3 mm, 1.4600-1.4610, in about 85% yield. 

A mixture of cyclohexanone (11.8 g, 0.12 mole), ethylene glycol (8.2 g, 0.13 mole), /j-toluenesulfonic acid monohydrate (0.05 g), and 50 ml of benzene is placed in a 250-ml round-bottom flask fitted with a water separator and a condenser (drying tube). The flask is refluxed (mantle) until the theoretical amount of water (approx. 2.2 ml) has collected in the separator trap. The cooled reaction mixture is washed with 20 ml of 10 % sodium hydroxide solution followed by five 10-ml washes with water, dried over anhydrous potassium carbonate, and filtered. The benzene is removed (rotary evaporator) and the residue is distilled, affording l,4-dioxaspiro[4.5]decane, bp 65-67713 mm, 1.4565-1.4575, in about 80% yield. 

II. 4-/-Butyicyclohexanone (Chapter 1, Section I) A l,4-Dioxaspiro[4.5]decane (Chapter 7, Section IX)... 

Chemical Name (1,4-Dioxaspiro[4.5l decan-2-ylmethyl)guanidine sulfate Common Name —... 

Dioxaspiro[4.5l decane-2-methylamine 2-Methyl-2-thiopseudourea sulfate... 

Based on the results of the hydrophobization of po-ly(MA-DP), we applied the hydrophobically grafting technique to poly(maleic acid-fl//-7,l2-dioxaspiro-[5,6]-... 

The method of preparing l,4 dioxaspiro[4.5]decane is that of Salmi.3 The methods used by Lorette and Howard4 to prepare ketals are convenient for preparing l,4-dioxaspiro[4.5]decane. 

Aluminum chloride, 45, 109 with lithium aluminum hydride, in reduction of l,4-dioxaspiro[4 5] decane 47, 37... 

The general features of the monensin synthesis conducted by Kishi et al. are outlined, in retrosynthetic format, in Scheme 1. It was decided to delay the construction of monensin s spiroketal substructure, the l,6-dioxaspiro[4.5]decane framework, to a very late stage in the synthesis (see Scheme 1). It seemed reasonable to expect that exposure of the keto triol resulting from the hydrogen-olysis of the C-5 benzyl ether in 2 to an acidic medium could, under equilibrating conditions, result in the formation of the spiroketal in 1. This proposition was based on the reasonable assumption that the configuration of the spiroketal carbon (C-9) in monensin corresponds to the thermodynamically most stable form, as is the case for most spiroketal-containing natural products.19 Spiro-ketals found in nature usually adopt conformations in which steric effects are minimized and anomeric effects are maximized. 

From intermediate 43, the path to monensin would seemingly be straightforward. A significant task which would remain would be the construction of the l,6-dioxaspiro[4.5]decane substructure of monensin. You will note that the oxygen atoms affixed to carbons 5 and 12 in 43 reside in proximity to the ketone carbonyl at C-9. In such a favorable setting, it is conceivable that the action of acid on 43 could induce cleavage of both triethylsilyl ethers to give a keto triol which could then participate in a spontaneous, thermodynamically controlled spiroketalization reaction. Saponification of the C-l methyl ester would then complete the synthesis of monensin. 

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. 

C15H14N2O6 - iy7J-96-iS) see Rosoxacin dimethyl 2,6-dimethoxyterephthalate (Ci2H 40(j 16849-68-6) see Brodimoprim 6,6-dimethyl-5,7-dioxaspiro[2.S]octane-4,8-dione (C]jH)(,04 5617-70-9) see Ketorolac... 

C14H23NO5 7574-86-9) see Dopexamine (25)-3-oxo-l,4-dioxaspiro[4.S]decane-2-acetic acid (C,oH 405 153011-57-5) see Orlistat 3-oxo-2,7-dioxa-5-thiabicyclo[2.2.1]heptane (C4H4O3S 161683-18-7) see Lamivudine 17-oxo-4-estrene... 

In alkaline solution, 3-bromo-2,2-bis(bromomethyl)propanol undergoes successive loss of bromide to produce 2,6-dioxaspiro(3,3)-heptane (Ezra et al. 2005) (Figure 1.25). 

Aldehydes and ketones also add to allenes to form oxetanes.ai0,111) Further reaction of the oxetanes produced with excited carbonyls results in dioxaspiro[3.3]heptane derivatives(111) ... 

Succinic anhydride is dimerised to 1,6-dioxaspiro [4.4] nonane-2,7-dione by heating with sodium hydroxide. Modification of an existing procedure by adding further sodium hydroxide after the initial reaction led to a severe exothermic reaction after heating for some 30 h which fused the glass flask to the heating mantle, probably at a temperature approaching 550°C. The reason for this was not known [1], At elevated temperatures and under influence of alkali, succinic acid condenses decarboxylatively beyond the dimeric spiroacetal, sometimes explosively. Contamination of the anhydride with base is to be avoided [2],... 

Polybia occidentalis W-VG Alarm (2S,6R,8S)-2,8-Dimethyl-1,7-dioxaspiro-[5.5] undecane 142 [188]... 

Haloetherification remains one of the most popular approaches towards tetrahydrofuran skeletons. Yus reported a double iodoetherification reaction promoted by a silver salt, affording l,7-dioxaspiro[4.5]decanes, and an example is shown in the scheme below <06T2264>. Kumar and Singh also reported an iodoetherification pathway to form 2,3-diphenyltetrahydrofurans <06T4018>. A bromoetherification converted 3-butenols into bromotetrahydrofurans <06TL5751>. 

---