Spiro-ethers

When a-tethered nitroalkenes bearing three or four methylene chains and ester-activated dipolarophiles react with vinyl ethers, spiro mode tandem cycloaddition takes place to give tricyclic spiro nitroso acetals in good yield and high diastereoselectivity (Scheme 8.46).184... 

Cyclohexanedione monoethylene acetal (l,4-dioxa-spiro[4.5]decan-8-one) [4746-97-8] M 156.2, m 70-73", 73.5-74.5". Recrystd from pet ether and sublimes slowly on attempted distillation. Also purified by dissolving in Et20 and adding pet ether (b 60-80°) until turbid and cool. [Gardner et al. J Am Chem Soc 22 1206 I957 Britten and Lockwood J Chem Soc Perkin Trans I 1824 1974.]... 

Crystd from benzene, CCI4, CH2CI2, EtOH, pet ether, acetone/pet ether and distd deionized water. Dried at 40° under vacuum over P2O5. Distd at low pressure. Also purified by sublimation or by zone melting. [Caswell and Spiro J Am Chem Soc 108 6470 1986.] N-imidazole was crystd from benzene [Scholes et al. J Am Chem Soc 108 1660 1986]. 

Spiro-pyrazoline derivatives (18) are obtained smoothly from 16-methy-lene-17-ketones (17). ° The sole products formed from (18) by pyrolysis or cleavage in the presence of boron trifluoride etherate, are the 16-spiro-cyclopropyl steroids (19). ... 

A-Homo-5a-cholestan-4-one (3b). A solution of sodium nitrite (2 g) in water (100 ml) is added over 1 hr to a stirred solution of 3-(5 -spiro-2, 2 -dimethyloxazolidinyl)-5a-cholestane (7 4.58 g) in aqueous 10% acetic acid (800 ml), maintained at 0-5° for 3 hr and the mixture is then allowed to stand overnight. The reaction mixture is neutralized with 10% sodium hydroxide solution and the resulting white suspension is extracted with ether. The ether extracts are washed with water, dried and concentrated to give a semisolid residue which is converted to the semicarbazone by warming in methanol solution (ca. 65 ml/g) with an excess of methanolic semicarbazide-acetate solution. The precipitate of semicarbazone is recrystallized from ethanol to give a white powder mp 239-241°. A solution of hydrochloric acid (50 ml) in ethanol (450 ml) is added to the semicarbazone and the mixture is heated at reflux for 1 hr. The clear solution is diluted with water (250 ml) and the... 

Serini reaction, 167 Simmons-Smith reaction, 107 Sodium acetylide, 138 Sodium bismuthate, 147, 149 Sodium bistrimethylsilylamide, 90 Sodium chloroacetylide, 68 Solvolytic cleavage of cyclic ethers, 267 3- (5 -Spiro-2, 2 -dimethyloxazolidi nyl) -cholestane, 360... 

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. 

The spiro aziridine 202 (Scheme 3.74) reacts with a catalytic amount of boron trifluoride etherate to give rise to ring-expanded compound 205 in almost quantitative yield [55]. A possible mechanism involving intermediates 203 and 204 was proposed. 

In a formal synthesis of fasicularin, the critical spirocyclic ketone intermediate 183 was obtained by use of the rearrangement reaction of the silyloxy epoxide 182, derived from the unsaturated alcohol 180. Alkene 180 was epoxidized with DMDO to produce epoxy alcohol 181 as a single diastereoisomer, which was transformed into the trimethyl silyl ether derivative 182. Treatment of 182 with HCU resulted in smooth ring-expansion to produce spiro compound 183, which was subsequently elaborated to the desired natural product (Scheme 8.46) [88]. 

The 1,3,4-oxadiazole 113 is formed from the azo compound 112 by the action of triphenylphosphine <96SL652>. A general synthesis of 1,3.4-oxadiazolines consists in boiling an acylhydrazone with an acid anhydride (e.g., Scheme 18) <95JHC1647>. 2-Alkoxy-2-amino-l,3,4-oxadiazolines are sources of alkoxy(amino)carbenes the spiro compound 114, for instance, decomposes in boiling benzene to nitrogen, acetone and the carbene 115, which was trapped as the phenyl ether 116 in the presence of phenol <96JA4214>. 

Additions of silylated ketene acetals to lactones such as valerolactone in the presence of triphenylmethyl perchlorate in combination with either allyltrimethylsilane 82, trimethylsilyl cyanide 18, or triethylsilane 84b, to afford substituted cyclic ethers in high yields have already been discussed in Section 4.8. Aldehydes or ketones such as cyclohexanone condense in a modified Sakurai-cyclization with the silylated homoallylic alcohol 640 in the presence of TMSOTf 20, via 641, to give unsaturated cyclic spiro ethers 642 and HMDSO 7, whereas the 0,0-diethyllactone acetal 643 gives, with 640, the spiroacetal 644 and ethoxytrimethylsilane 13b [176-181]... 

Acetalization or ketalization with silylated glycols or 1,3-propanediols and the formation of thioketals by use of silylated 1,2-ethylenedithiols and silylated 2-mer-captoethylamines have already been discussed in Sections 5.1.1 and 5.1.5. For cyclizations of ketones such as cyclohexanone or of benzaldehyde dimethyl acetal 121 with co-silyl oxyallyltrimethylsilanes 640 to form unsaturated spiro ethers 642 and substituted tetrahydrofurans such as 647, see also Section 5.1.4. (cf. also the reaction of 654 to give 655 in Section 5.2) Likewise, Sila-Pummerer cyclizations have been discussed in Chapter 8 (Schemes 8.17-8.20). 

Giomi s group developed a domino process for the synthesis of spiro tricyclic nitroso acetals using a, 3-unsaturated nitro compounds 4-163 and ethyl vinyl ether to give the nitrone 4-164, which underwent a second 1,3-dipolar cycloaddition with the enol ether (Scheme 4.35) [56]. The diastereomeric cycloadducts formed, 4-165 and 4-166 can be isolated in high yield. However, if R is hydrogen, an elimination process follows to give the acetals 4-167 in 56% yield. 

The spiro-derivative (206) forms anhydrous complexes with larger alkali ions (such as K+). Such complexes appear to have a 2 1 structure of type (207) (Weber, 1979). For Li+, the hydrated complex [Li2L(H20)4]l2 [where L = (206)] is formed. The X-ray structure of this species reveals that it is essentially of type (207) except that the Li+ in each macro-ring coordinates to only three ether oxygens of the ring. Each Li+... 

The residue was purified by flash chromatography using petroleum ether-diethyl ether (9 1) as eluent to give (IS, VR)-1.2.3.4-tetrahydro-3,-/.v propyl-spiro [naphthalene-2,2 -oxirane]-l-one as a yellow oil (190 mg, 0.88 mmol, 90%). 

Cyclopentenones. 1,3-Dicarbonyl compounds add to enol ethers or esters (terminal) in the presence of Mn30(OAc)7 (excess) to form l-alkoxy-l,2-dihydro-furans. These can be converted to a 1,4-diketone, which undergoes aldol cyclization to fused (or spiro) cyclopentenones.1... 

Organobis(cupratesY, spiroannelation.16 1,4-Dilithiobutane, prepared from 1,4-dichlorobutane and lithium in ether at 0°, on reaction with copper thiophenoxide (2 equiv.) forms a biscuprate, formulated as 1 for convenience. This dimetallic reagent adds to 3-halo-5,5-dimethyl-2-cyclohexenones (2) to form the spiro-[4.5]decanone 3 in yields as high as 96%. Cuprates prepared from other Cu(I) sources are less efficient, as is the cuprate prepared from di-Grignard reagents... 

When comparing these results with those previously obtained using carbohydrate-based vinyl ethers as chiral dienophiles, this improved facial diastereoselectivity to heterodienes under similar conditions is noteworthy.81 The efficient chiral transfer in the second example might mostly be attributed to the specific architecture of the l,2 5,6-di-0-isopropylidene-a-D-glucofuranose moiety.Those findings open the way to develop well-defined spiro-carbohydrate templates towards improved auxiliaries for chirality transfer in a wide range of syntheses. 

Sattelkau and Eilbracht90 have exploited the Claisen rearrangement of allyl vinyl ethers in their synthesis of several spiro compounds. As shown below in equation 62, 7,9-dimethyl-l,4-dioxa-spiro[4,5]decan-8-one, 118, was converted to a ,/J-unsaturated ester 119 which was reduced to allyl alcohol 120906. Allyl vinyl ether 121 underwent a rhodium-catalyzed Claisen rearrangement to afford 7r,13r-dimethyl-l,4-dioxa-(8rC9)-dispiro[4.2.4.2]tetradecan-10-one (122) in 36% yield. 

Reinstallation of the fractured spiro ring can be accomplished either directly at the enone level or, more interestingly, after the ketone carbonyl has been capped as in 36. When 36 and stereoisomers thereof are individually subjected to intramolecular oxymercuration, the stereochemical course of the cyclization is dictated by the approach of Hg2+ to that surface of the double bond where coordination to a proximal axially oriented ether oxygen can operate. [31] Where 37 and 40 are concerned,... 

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