Spiro-rearrangement

The mechanism of cyclization of the aminonitrile to the 3-arylisoquinolin-4-one involves a spiro rearrangement with both anhydrous HF and sulfuric acid [87JCR(S)36] whereby an ortho or para oxygenated substituent is involved in the initial cyclization step with subsequent bond breakage to... 

Dunham and Lawton have suggested an alternative biogenesis for the eremophilane sesquiterpenes via a series of four decalyl spiro rearrangements, a process which effectively shifts the position of the methyl group from one angular position to the other (238). This proposal has the disadvantage of requiring a cw-fused eudesmane precursor, a known (occidentalol), but rare stereochemical variant, and, at least in the case of capsidiol is excluded by recent biosynthetic results (229). 

Both spiro and methyl migration rearrangements are proposed to occur when the pentamethyloctalin 153 is subjected to reaction with sulfuric acid in acetic acid (239). Isomers 154 and 155 are formed by decalyl spiro rearrangement followed by angular methyl shift and elimination. The minor product 156 however, arises by direct methyl migration. 

Antithetic conversion of a TGT by molecular rearrangement into a symmetrical precursor with the possibility for disconnection into two identical molecules. This case can be illustrated by the application of the Wittig rearrangement transform which converts 139 to 140 or the pinacol rearrangement transform which changes spiro ketone 141 into diol 142. 

The pinacol rearrangement reaction is of limited synthetic importance although it can be a useful alternative to the standard methods for synthesis of aldehydes and ketones." Especially in the synthesis of ketones with special substitution pattern—e.g. a spiro ketone like 5—the pinacol rearrangement demonstrates its synthetic potential ... 

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]. 

Pirkle, W. H. Smith, S. G. Koser, G. F. Stereospecificity and wavelength dependence in the photochemical rearrangement of spiro[2.5]octa-4,7-dien-6-ones to quinone methides. j. Am. Chem. Soc. 1969, 91, 1580-1582. 

Nowhere, perhaps, is this phenomenon better illustrated than in the phenothiazine class. The earlier volume devoted a full chapter to the discussion of this important structural class, which was represented by both major tranquilizers and antihistamines. The lone phenothiazine below, flutiazin (130), in fact fails to show the activities characteristic of its class. Instead, the ring system is used as the aromatic nucleus for a nonsteroidal antiinflammatory agent. Preparation of 130 starts with formylation of the rather complex aniline 123. Reaction with alcoholic sodium hydroxide results in net overall transformation to the phenothiazine by the Smiles rearrangement. The sequence begins with formation of the anion on the amide nitrogen addition to the carbon bearing sulfur affords the corresponding transient spiro intermediate 126. Rearomatization... 

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. 

The initially formed cyclopropyl ketones from the photolysis of cross-conjugated cyclohexadienones are also photolabile. Usually the photochemical rearrangements of cyclopropyl ketones involve cleavage of the cyclopropyl bond which forms part of the cyclopentenone ring followed by either (a) a substituent migration or (b) rearrangement through a spiro intermediate. While the literature in this area is too voluminous to review in... 

The obtained spiro keto esters 2-181 could be converted into 2-183, employing among other transformations an intramolecular Schmidt rearrangement [101] of the azido ketones 2-182. 

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... 

Treatment of the tetrahydropyrano[l,6]naphthyridine 303 with phosphorus oxychloride results both in closure of the imidazole ring and rearrangement of the pyran ring to give the spiro-cyclopropano compound 304 (Equation 104) <1996JHC49>. 

Acylation of the tryptamine-based /3-enamino esters 458 with acryloyl chloride and its derivatives results in acylation of the enamine nitrogen and formation of the pyridiniminium ion intermediate 459. Electrophilic attack at C-3 of the indole and rearrangement of the spiro intermediate gives the indoloquinolizines 460 (Scheme 102) <2003TL6527>. 

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