Lactones spiro-, rearrangement

Halogen substitution is expected to increase the electrophilicity of the carbenes, and in particular lh with four fluorine substituents is expected to be highly electrophilic and of unusual reactivity. All the carbenes le-g could be matrix-isolated by irradiation of their corresponding quinone diazides 2 in argon at 8-10 K.24 68,62 Again, the thermal reaction in (Vdoped matrices results in the formation of quinone oxides 7, which show the expected photochemical rearrangement to the spiro dioxiranes 8 and finally lactones 9. 

In 2001, Albrecht Berkessel and Nadine Vogl reported on the Baeyer-Villiger oxidation with hydrogen peroxide in 1,1,1,3,3,3-hexafluoroisopropanol (HFIP) as solvent in the presence of Brpnsted acid catalysts such as para-toluenesulfonic acid (equation 85) . Under these conditions cyclohexanone could be selectively transformed into the corresponding lactone within 40 min at 60 °C with a yield of 92%. Mechanistic investigations of Berkessel and coworkers revealed that this reaction in HFIP proceeds by a new mechanism, via spiro-bisperoxide 234 as intermediate, which then rearranges to form the lactone. The study illustrates the importance of HFIP as solvent for the reaction, which presumably allows the cationic rearrangement of the tetroxane intermediates. 

Whereas a triplet 1,4-biradical has been assigned as the most probable intermediate at that time, later work on intramolecular trapping reaction favored the assumption of radical ion pairs [46]. Efficient lactonization reaction to form 51 during irradiation of pent-4-enoic acid 50 and 48 accounts for an olefin radical cation which undergoes electrophilic addition towards the carboxyl group. Another type of rearrangement has been detected in the photoreaction of tetramethylallene and 48 [47]. 5-Hydroxy-indan-2-ones 52 are formed in high yields probably via instable spiro-oxetanes 49b as intermediates. 

In fluorinated alcohol solvents, nonstrained ketones such as cyclohexanone (1) undergo oxidation to lactones in the presence of hydrogen peroxide and catalytic amounts of Brpnsted acids (Berkessel and An-dreae 2001 Berkessel et al. 2002). Unlike the classical Baeyer-Villiger reaction, ketone oxidation with H2O2 in e.g. HFIP proceeds via a spiro-bisperoxide 2 intermediate (Scheme 1). In contrast to other solvents, the acid-catalyzed rearrangement of the spiro-bisperoxide 2 to two equivalents of the product lactone 3 proceeds rapidly and cleanly in HFIP. Preliminary calculations indicate active participation of the fluorinated alcohol solvent in the rate-determining step also in this case. 

Scheme 1. Top formation of the spiro-bisperoxide 2 from cyclohexanone (1) and hydrogen peroxide. Bottom suggested mechanism of the acid-catalyzed rearrangement of the spiro-bisperoxide 2 to two molecules of the product lactone 3...

Benzenesulfenyl chloride can convm unsaturated adds to lactones. The unsatuiated add (7) is treated with benzenesulfenyl chloride, followed by Raney nickel, to afford the 7-lactone (8) in excdlent overall yield (equation 5). Another acid (9) has been lactonized to produce the spiro-p-lactone (10) whidi rearranges on silica gel to 7-lactone (11 equation 6). 6-Lactones have been also prqrared using diis rq>-proach. An additional advantage of this approach is that the phenyl sulfide moiety can be manipulated into a variety of functional groups to facilitate cyclization. in suirunary, successfiil cyclization reactions... 

Levopimaric acid forms an epidioxide (63) which thermally rearranges to a di oxide (65). On photolysis the epidioxide gives both the diepoxide and the 12-keto-epoxide (64). Treatment of the epidioxide with triphenylphosphine affords a monoepoxide which was shown to be the 8a(14a)-epoxide (66). On further epoxidation this gave the diepoxide, levopimaric acid dioxide. The photochemistry of ring c diterpenoid y-hydroxydienones has also been investi-gated. " Thus compound (67 R = H or Et) afforded firstly the spiro-diketone (68) and then the unsaturated y-lactone (69). 

The final main group of structures is composed of spirobiflavonoids (442-447) spirobiflavonoids made up of two C15 units (448-449) phenolic spiro derivatives derived from C15 and C14 units (450) a C15 moiety of flavonoid origin and a Ci4-stilbene substructure linked via a y-lactone ring (attachment of the stilbene derivative to the carbocation intermediate of the oxidation of flavanone to flavanol, and subsequent rearrangement of this intermediate) (451-452) and a C15 moiety of flavonoid origin and a Cu-stilbene substructure linked via a y-laetone ring (453-455). 

Saponification, methylation, and heating in DMSO/NaCl124 afford rearrangement to the spiro lactones 202123 (See Scheme 50). However, direct treatment of lactone 203 with DMSO/NaCl leads under elimination of HNCO to phenylureidobutenolides 204.123... 

Three independent syntheses of the cubebane-type skeleton have been reported in which formation of the cyclopropane ring was once again achieved by an internal diazoketone cyclisation. In the first of these syntheses, Yoshikoshi et utilised (—)-trans-caran-2-one as the starting material which was converted in three steps to the spiro-lactone (83). Pyrolytic rearrangement of this compound to the key olefin-acid (84) was accomplished in 70% yield. Conversion to the corresponding diazoketone, followed by decomposition yielded the tricyclic ketone (85, R = O) and its stereoisomer (86). Standard procedures converted... 

Treatment of the /3-lactones (66) with MgBf2 in ether at room temperature brings about quantitative, stereospecific conversion into y-lactones by a novel dyotropic Wagner-Meerwein rearrangement this is a reaction of considerable synthetic potential. A number of additions e.g. of nitrenes, carbenes, and diazo-compounds) to diketen to give spiro-/3-lactones, which can be further transformed, have been described.For example, photolysis of acyl azides in the presence of diketen leads to pyrrolinone derivatives (67), presumably as shown.With phenyl(trichloromethyl)mercury, the spiro-lactone (68), in which... 

There are two ways in which the cosynthetase enzyme could turn the fourth PBG unit around. Battersby believes an enzyme-bound spiro-intermediate is formed, which goes on to form uro gen 111. ° An alternative proposal, by Ian Scott at Texas A M University, is that the cleaved hydroxybilane intermediate self-assembles to form a lactone via the acetic acid side chain at position 17 in ring D. Although support for this view comes from the observation that synthetic bilanes without this side chain will not undergo enzyme-catalysed rearrangement to the type III isomer, the weight of experimental evidence seems to support Battersby s spiro-... 

On heating in methylene chloride, the cyclopropenylium cyclopropene (633) rearranges to the spiro[2,3]hexadienylium system (634), which can be trapped as (635 R = OH or OMe) by addition of water or methanol. The alcohol (635 R = OH) is converted by thionyl chloride into the chloride (635 R = Cl) and the latter can be transformed back into the spiro-cation (634) with silver ion. Manganese dioxide oxidation of the alcohol (635 R = OH) affords the lactone (636) rather than (637). The spiro-cation (634) cannot be converted back into (633X nor does it isomerize to the Dewar-benzene cation, presumably because of the bisected conformation of the cyclopropane double bond and the allyl cation moiety. ... 

Molecular rearrangement based thermochromic materials include spiro-lactones, fluorans, spiropyrans, and fulgides. These thermochromic materials normally consist of three components a dye precursor, a colour developer and a non-polar solvent. The colourless dye precursor and colour developer are both microencapsulated. Figure 14.6 shows the rearrangement of the molecular structure of spirolactone, which leads to the reversible thermochromic effect. A proton is donated to the spirolactone by the colour developer to form the dye. Before applying to textiles, thermochromic materials are normally encapsulated. Under some temperatures, bisphenol A emits proton, and crystal violet lactone opens rings and combines with the proton to make n system and shows colour. The colour varies with the substituent when it is H, the colour is violet when R is CH3 and X is OCH3, the colour is blue. 

Cameron, A. F., J. D. Connolly, A. Maltz, and D. A. H. Taylor Tetranor-triterpenoids and Related Compounds. Part 21. The Crystal and Molecular Structure of a Rearranged Tetranortriterpenoid Spiro-lactone from the Bark of Carapa procera (Meliaceae). Tetrahedron Letters 1979, 967. 

These results led to the postulation of the spirocyclic erythrinane skeleton and this was confirmed by synthesis of the parent nucleus by Belleau (1953). The structures of the two lactonic alkaloids (3) were also elucidated by Boekelheide (1960) and coworkers, who recognised their close structural identity to the other aromatic erythrina alkaloids (1) the lactonic alkaloids also underwent an apo -type rearrangement under drastic acidic conditions. Subsequently the structures of both the aromatic and lactonic alkaloids were confirmed by X-ray crystallography of erythra-line hydrobromide (Nowacki and Bonsma 1958) and of the erythroidines (Hanson 1963). The spiro centre was shown to have the same configuration in all the erythrina alkaloids by use of optical rotatory measurements (Weiss and Ziffer 1963, Beecham 1971). 

SCHEME 53. Microwave-assisted diastereoselective synthesis of a a-spiro-8-lactone via a WoUf rearrangement/a-oxo ketene trapping/cross-metathesis/intramolecular Michael addition consecutive sequence. 

The synthesis of alpinine illustrates a different approach to rhoeadine alkaloids, and is based on the photosensitized oxidation of the enaminoketone (A) and rearrangement of the resuiting dioxetan to a spiro keto lactone (B). The rest of the synthesis closely follows the pathway laid down earlier at Hoffman-La Roche for the synthesis of rhoeadine. ... 

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