Spiro compounds rearrangement

Also. 77/-pyrrolo[l,2-fl]azepin-7-ones, e.g. 22, available by the thermal rearrangement of 1-azaspiro[4.5]dcca-l,3,6,9-tetraen-8-ones 21, in trifluoroacetic acid form the deep-blue 7-hy-droxypyrrolo[l,2-tf]azepinium cations, e.g. 23.219 In hot 48 % hydrobromic acid, however, the spiro compound 21 is re-formed. 

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]. 

Kano et al. (161,162) also investigated the Stevens rearrangement of tetrahydroprotoberberine metho salts 302 with dimsylsodium and obtained the spirobenzylisoquinolines 303 in high yield (Scheme 56). Similarly C-homoprotoberberine 304 gave the new spiro compound 305, whereas B-homoprotoberberine 306 afforded only the Hofmann degradation product 307. 

Knolker and coworkers also used a domino [3+2] cycloaddition for the clever formation of a bridged tetracyclic compound 4-172, starting from a cyclopentanone 4-168 and containing two exocydic double bonds in the a-positions (Scheme 4.36) [57]. The reaction of 4-168 with an excess of allylsilane 4-169 in the presence of the Lewis acid TiCLj led to the spiro compound 4-170 in a syn fashion. It follows a Wag-ner-Meerwein rearrangement to give a tertiary carbocation 4-171, which acts as an electrophile in an electrophilic aromatic substitution process. The final step is the... 

An interesting strategy for the synthesis of pyrrolizidines and indolizidines has been developed by Brandi and co-workers. Cycloaddition between nitrones or nitrile oxides with methylenecyclopropanes generates strained tricyclic spiro compounds, which are prone toward further transformations, such as rearrangement, ring opening, and new ring closure (Scheme 10.17).116... 

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. 

An acid-rhenium catalyst mixture acts on ( )-4-(4-hydroxyphenyl)butan-2-one oxime (44) to produce a high yield of the spiro compound (45), which then rearranges to the substituted quinoline (46)." ° The Beckmann rearrangement product (47)... 

An interesting spiro compound (59) that contains the thietane ring was obtained in minor amounts by dimerization of dimethylketene and subsequent treatment with P2S5. Pyrolysis of the spiro structure produced 60 and the thietanethione 61, which can also be prepared by base-catalyzed rearrangement of 62, a process that can be carried out as well with 63 to give the 2-thietanone 60. The solvent and the basicity of the catalyst are important parameters in this rearrangement. 

Expecting that acidic isomerization involving a double Wagner-Meerwein rearrangement would transform the bicyclic olefin 74 into supposedly stable [10.10]betweena-nene and its (Z)[10.10] isomer, they treated 74 with H2S04-AcOH in benzene only to find that the product was an 85 15 mixture of 75 and 76. Solvolysis of the spiro compound 77 was also found to yield a 60 40 mixture of 75 and 76 which was totally free from the fused (Z)[10.10] and ( )[10.10] olefins. 

A methanobridge is also formed when 1-hydroxymethylhexahelicene (93) is treated with an acid, but in this case the primary product (94) rearranges into the spiro compound (95). The same product is formed when (93) is heated in hexachloroethane at 200 °C for 30 min, either in the presence or absence of trifluoroacetic acid, but not in naphthalene as the solvent under the same conditions 163). 

Diazopyrrole 196 with diethyl acetylenedicarboxylate gives the spiro compound 197. Rearrangement of 197 gives the pyrazolo[l,5-c]pyrimidine 198 (74LA1550). 

Nearly all examples of epoxidation of alkylidenecyclobutanes involve 3-chloroperoxybenzoic acid.15 58-70 This is because the conditions are mild, the workup is easy and few byproducts are formed. Generally, dichloromethane or chloroform is used as solvent. Solid sodium hydrogen carbonate is occasionally added to avoid acid-catalyzed rearrangement of the spiro compound. For example, 6-isopropylidene-l,4,4-trimethylbicyclo[3.2.0]heptan-3-one reacted with 3-chloroperoxybenzoic acid and sodium hydrogen carbonate to give 2,2,3, 3, 6-pentamethyl-spiro[3-oxabicyclo[4.2.0]octane-8,2 -oxirane]-4-one (4) in quantitative yield. However, without the use of sodium hydrogen carbonate, substantial amounts of 2,2,6,9,9-pentamethyl-3-oxa-bicyclo[4.3.0]nonane-4,8-dione (5) and 2,2,6,8,8-pentamethyl-3-oxabicyclo[4.3.0]nonane-4,9-dione (6) were also formed.15-64... 

Examples 5 and 8 both involve vinylcyclobutane moieties. An interesting vinylcyclobutane rearrangement leading to novel spiro compound 11 was observed when cyclobutene trimer 10 was reacted with cesium fluoride in dimethylformamide at room temperature.37-38 Possible mechanisms for this unique isomerization have been proposed.38... 

The reaction with pyridone (167) was interpreted as proceeding by the formation of the pyridone (168), followed by the Smiles rearrangement leading to the spiro compound (169), which by ring opening provides the pyrimidine derivative (170). In a subsequent cyclization step the pyrido-[1,2-aJpyrimidine skeleton (171) is formed, and finally hydrolysis of the imino group leads to the 6-oxo derivative (172). In the homologous imidazo-[l,2-n]pyridine series, the 5-iminoimidazo[l,2-c<]pyridine intermediate of type (171) could be isolated. 

It is not quite clear whether the spiro compounds 83 are obtained by a normal Diels-Alder reaction, since it could also be formed by a Claisen rearrangement occurring on adduct 82. Actually, heating of the trans-fused adduct 82 in EtOH at reflux for 12 h led to 83a with 65% conversion. On the other hand, the as-fused adduct 78c was completely stable under these conditions. Therefore, the 5 1 ratio... 

The palladium-catalyzed reductive N-heteroannulation using carbon monoxide has been reported (Scheme 102). As part of this study, substrate 551 was examined in an attempt to synthesize 552. However, 552 was found to be unstable and underwent further oxidative rearrangement in air to form spiro compound 555 via intermediates 553 and 554 <2006T10829>. 

Heating N- acetyl-5- (a-ketoalkyl)cysteine (308) for a brief period with acetic anhydride gives dihydro-2-methylthieno[3,4-d]oxazole-3a(4//)-carboxylic acids (310) (79JOC825). While the mechanism has not been investigated in detail, the isolation of several compounds suggests the existence of the intermediate spiro compound (309). Rearrangement to (310) is feasible since the anhydride character of (309) is changed to the ester character of (310). 

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