Spiro compounds spirocyclic

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 first cyclization of a-hydroxyalkoxyallenes goes back to the pioneering experiments of Brandsma, Hoff and Arens, who found that dihydrofuran derivatives 102 are formed by treatment of 101 with KOtBu in DMSO (Scheme 8.26) [12c], This reaction protocol was successfully applied by others [61, 63, 64, 80-83], for example in the preparation of spiro compound 104 (Eq. 8.19) [83] and in the cyclization of 64 leading to a-amino acid-derived dihydrofurans 105 (Scheme 8.27) [61, 63], Acidic hydrolysis of dihydrofurans furnished 3(2H)-dihydrofuranones, which could be used again as carbonyl components in the repetitive addition of lithiated methoxyal-lene 42. This concept was employed in syntheses of racemic [82] and enantiomeri-cally pure [64] primary helical spirocycles. 

Bischof and Mattay have shown that radical anion cyclization leading to spirocyclic products compete effectively with intramolecular [2 -f 2]-cycloaddition on photoexcitation of olefinic enones in the presence of triethylamine [332, 333]. The [2 -f 2] cycloadducts could be converted to the corresponding spiro compounds under PET conditions (Scheme 75) [307]. 

The exocyclic C=S bond of 5-thioxo-2-thiazolines (203) can act as a dipolarophile towards several compounds. For instance, cycloaddition reactions have been reported with nitrilium betaines (204) to give heterocyclic spiro compounds <84HCA534>, with thiocarbonyl ylides (205) to give spirocyclic 1,3-dithiolanes <9IHCA1386>, and with 2-diazopropane (206) to give thiadiazoles <92HCA1825>. On the other hand, the reaction of (203) with diazomethane leads to a mixture of five products (Scheme 49) <93hcai715>. 

The Diels-Alder reaction is undoubtedly a very useful route to spirocyclic compounds, and has now been extended to allenic ketones, so giving ready access to polyfunctional spiro-systems as shown in the preparation of (132). Furan-terminated cationic cycliza-tions have been applied to the synthesis of spiro-compounds such as... 

General Procedure for the Preparation Spirocyclic Compounds 59 by Rios [30] In a small flask, oxindole 58 (0.25 mmol, 1 equiv) and a,p-unsaturated aldehyde 16 (0.75 mmol, 1.5 equiv) were stirred in toluene at room temperature in the presence of catalyst I (0.05 mmol, 0.2 equiv) and benzoic acid (0.05 mmol, 0.2 equiv). The reaction was stirred overnight, monitored by NMR. Then, the crude mixture was purified by column chromatography to afford the spiro compounds 59. 

Wang and coworkers developed an intriguing strategy for the inverse-electron-demand Diels-Alder reaction to afford spiro compounds [51]. The reaction of a cyclopentyl keto-enolate salt 89 with A-tosyl-2-methylenebut-3-enoate 88 was catalyzed by the bifunctional primary amine-thiourea catalyst derived from rosin XXII to afford the spirocycles 90 in excellent yields (85-99%), excellent diastereoselec-tivities (up to >20 1 dr), and excellent enantioselectivities (90-99%, Scheme 10.31). 

For a review about enantioselective methodologies for the synthesis of spirocyclic compounds, see Rios, R. (2012). Enantioselective methodologies for the synthesis of spiro compounds. Chemical Society Reviews, 41,1060-1074. 

Spiro compounds s. a. Di-(spiroazonia)compounds, Metalcarbonyl-phosphorus complex compounds, spiro-cyclic Trispirobis-2,5-cyclohexadienones fcfra-jHcf-Spirocyclics s. Tetrathiospirocyclics 4,5 -Spiro-d diisoxazolines, ring opening, preferential 21, 981... 

Stockman and coworkers [329] developed a straightforward synthesis of a tricyclic compound 2-636 which has some resemblance to the spirocyclic portion of the natural product halichlorine (2-637) [330]. On treatment of the symmetrical ketone 2-633, accessible in five steps from alcohol 2-632, with hydroxylamine hydrochloride the spiro piperidine 2-636 could be obtained in 62% yield (Scheme... 

P nuclear magnetic resonance (NMR) spectroscopy has been of great use in determining the coordination state and stereochemistry of the phosphorus atom at the spiro position in spirophosphonia compounds, spirophosphoranes and spiroperphosporanides. The 31P chemical shift is also sensitive to the nature of the atoms directly bonded to the spiro phosphorus center and the size of rings of the spirocyclic system. 

The synthesis and stmctnral characterization of a series of spirocyclic organozincates containing two five- or six-membered metallacycles in which zinc is the central spiro atom, is shown in Scheme 1. Compound 8a was prepared via an elegant one-pot synthesis, starting from 1,5-dichloropentane, ZnCl2 and a lithium/sodinm alloy (1% sodinm) in diethyl ether as a solvent (eqnation 4 in Scheme 1). Snbseqnent treatment of a soln-tion of 8a with TMEDA afforded the corresponding TMEDA complex 8b of which the structnre in the solid state was unambiguously established by an X-ray crystal structnre determination. 

The final, critical oxidative spirocyclization of the 2,3-disubstituted indole to the spiro oxindole was effected by treatment of 124 with tert-butyl hypochlorite in pyridine to provide the labile 125 [Fig. (34)]. The Pinacol-type rearrangement was conducted by treating compound 125 with p-toluenesulfonic acid in THF/water. It is assumed that the chlorination of 124 proceeds from the least hindered face of the indole, to give the a-chloroindolene 125. The hydration of the imine functionality must also occur from the same a-face that is syn to the relatively large chlorine atom furnishing the syn-chlorohydrin 126, that subsequently rearranges stereospecifically to the desired spiro oxindole 127. 

The first structural report of an alumo-poly siloxane appeared as early as 1966 the molecule (Me2SiO)4(OAlBr2)2(AlBr) has an Si4Al2Ofi 12-membered cycle which is spirocyclically bridged by an Al-Br unit (see Fig. 3).68 Only in 2000 was the corresponding structure of the chloro-derivative (which is iso-typic to the bromo-compond) published.69 In both compounds, all silicon and aluminum atoms are tetra-coordinate with the exception of the spiro-cyclic central bromo(chloro)-aluminum -moiety, which is penta-coordinate with four oxygen bonds. 

The defence secretion of the milliped Polyzonium rosalbum contains the spiro-monoterpenoid polyzonimine (35) 97 the isolation of the spirocyclic nitro-compound (36)98 might suggest a non-geranyl pyrophosphate biogenetic route from a pyr-rolizidine alkaloid. The production of verbenone in the bark beetle Dendroctonus sp. may be associated with chemical communication.99... 

A number of new five-co-ordinate spiro-phosphoranes such as (102), obtained from P(NMe2)s and ephedrine," " and (103)" have also been synthesized. In compound (104), replacement of the dimethylamino-group with both mono- and di-hydroxy species has been studied,and i.r. investigations on a number of similar compounds, but containing P—H bonds point to the establishment of the equilibrium in equation (51) between the phosphorus(v) spirocyclic form and an... 

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>. 

Spiroproline derivatives are of interest in biological studies as an inhibitor and mechanistic probe of prolyl-4-hydroxylase. To develop potent inhibitors of angiotensinconverting enzyme (ACE), lipophilic and sterically hindered spiroproline derivatives have been substituted in the structural framework of peptides. In addition, spiroprolines could offer interesting scaffold precursors, particularly in synthesis of combinatorial libraries of peptides. Earlier synthetic efforts aimed at spiroproline analogs involved building the proline nucleus on the structural backbone of the alicyclic system followed by resolution. We decided to try to expand the potential of our synthesis of spirocyclic compounds to pro-line derivatives, with the hitherto unknown 2-aza-spiro[4.4]-nonane carboxylic acid (124) derivative as the target. 

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