Spiro lactones, formation

Homoenolate Reactivity The ability to generate homoenolates from enals and its application to the preparation of y-butyrolactones 30, through reaction with an aldehyde or aryl trifluoromethyl ketone, was reported independently by Glorius [8], and Bode and Burstein [9] (Scheme 12.4). A sterically demanding NHC catalyst is required to promote reactivity at the d terminus and to prevent competitive benzoin dimerisation. Nair and co-workers have reported a similar spiro-y-lactone formation reaction using cyclic 1,2-diones, including cyclohexane-1,2-dione and substituted isatin derivatives [10]. 

Crabb and Schofield8 likewise reported formation of a spiro-lactone during the attempted epoxidation of certain benzocydo-... 

The course of the reaction may be considered to follow either path a or path b. By analogy to the proposed mechanism of formation of the spiro-lactone of dioxindolepropionic acid (XCI — XCIII), the concerted displacement reaction (path a) is preferred to the displacement of a C-bromo atom in a tribromodienone (path b). 

The spiro-lactone structure of isopropylidene 1,1-cyclopropanedicarboxylates 7 increases the electrophilic character of the cyclopropane ring. When isopropylidene 1,1-cyclopropanedi-carboxylate was heated in aqueous acetone, water was added across the proximal C-C bond of the ring followed by the formation of y-lactone 8 and hydrolysis of the second ester function. The corresponding bicyclo[4.1.0]heptanedicarboxylate reacted in the same fashion to afford the tra 5-lactone as a result of an inversion of configuration upon the nucleophilic attack by water. °... 

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... 

Startg. 7-hydroxyamide treated 3-4 hrs. with ice-cooled 70%-HC104 spiro-[2-phenylphthalimidine-3,l -cyclohexane]. Y 77%. F. e., also with coned. H2SO4 and lactone formation, s. C.-L. Mao, I. T. Barnish, and C. R. Hauser, J. Heterocyclic Chem. 6, 475 (1969). 

In the presence of a double bond at a suitable position, the CO insertion is followed by alkene insertion. In the intramolecular reaction of 552, different products, 553 and 554, are obtained by the use of diflerent catalytic spe-cies[408,409]. Pd(dba)2 in the absence of Ph,P affords 554. PdCl2(Ph3P)3 affords the spiro p-keto ester 553. The carbonylation of o-methallylbenzyl chloride (555) produced the benzoannulated enol lactone 556 by CO, alkene. and CO insertions. In addition, the cyclobutanone derivative 558 was obtained as a byproduct via the cycloaddition of the ketene intermediate 557[4I0]. Another type of intramolecular enone formation is used for the formation of the heterocyclic compounds 559[4l I]. The carbonylation of the I-iodo-1,4-diene 560 produces the cyclopentenone 561 by CO. alkene. and CO insertions[409,4l2]. 

Volatiles or Aroma. The essential oil, or aroma, of tea provides much of the pleasing flavor and scent of green and black tea beverages. Despite this, volatile components comprise only - 1% of the total mass of the tea leaves and tea infusions. Black tea aroma contains over 300 characterizing compounds, the most important of which are terpenes, terpene alcohols, lactones, ketones, esters, and spiro compounds (30). The mechanisms for the formation of these important tea compounds are not fully understood. The respective chemistries of the aroma constituents of tea have been reviewed... 

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. 

Addition of diols to the carbonyl lactone group leads to the formation of cyclic orthoesters. Compounds containing a spiro, cyclic orthoester inter-linkage at the anomeric carbon atom are of interest, as this type of structure is found in the oligosaccharide antibiotics orthosomycins (91) (such as ever-ninomicin, flambamycin, and avilamycin). 

The proposed formation of 2,5-benzothiazocine-l,6-diones (114 R = Pr) from the reaction of phthaloyl chloride (112) and amidino thioamides (113 R = Pr, Ar = 4-O2NC6H4, 4-MeOC6H4) in pyridine has been disproved. Instead, supported by an X-ray structure, the products have been shown to be spiro[4,4]lactones (116 R = Pr, Ar = 4-O2NC6H4, 4-MeOCeH4). The proposed mechanism of formation of... 

Selectivity for the formation of 207 is dramatically improved by use of either a stronger base, such as 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) instead of EtsN (0.1 molar equiv. of DBU is sufficient for selective formation of 205), or a bulkier silane, such as Bu Me2SiH. The spiro-typc /3-lactones 207, 208, and 209 are also obtained in good... 

Spiroannelation.2 Acylation of 1 by the cnol lactone 2 results in formation of only one (3) of the two possible spiro[4.5]decenes. The hulky isopropyl group is... 

It is in this area of dienone photochemistry that the effect of structure on reactivities of excited states seems to be especially complex. For example, Kropp has shown that the presence of the 4-methyl group in santonin is responsible for preferential formation of the fused 5,7 ring system in photosantonic lactone.403 An analogous cross-conjugated dienone with a 2-methyl substituent yields only a spiro compound in acidic media,404 while a dienone with neither 2- nor 4-substituents yields mixtures of the two types of products.409... 

Chlorophenyl)glutarate monoethyl ester 87 was reduced to hydroxy acid and subsequently cyclized to afford lactone 88. This was further submitted to reduction with diisobutylaluminium hydride to provide lactol followed by Homer-Emmons reaction, which resulted in the formation of hydroxy ester product 89 in good yield. The alcohol was protected as silyl ether and the double bond in 89 was reduced with magnesium powder in methanol to provide methyl ester 90. The hydrolysis to the acid and condensation of the acid chloride with Evans s chiral auxiliary provided product 91, which was further converted to titanium enolate on reaction with TiCI. This was submitted to enolate-imine condensation in the presence of amine to afford 92. The silylation of the 92 with N, O-bis(trimethylsilyl) acetamide followed by treatment with tetrabutylammonium fluoride resulted in cyclization to form the azetidin-2-one ring and subsequently hydrolysis provided 93. This product was converted to bromide analog, which on treatment with LDA underwent intramolecular cyclization to afford the cholesterol absorption inhibitor spiro-(3-lactam (+)-SCH 54016 94. 

The deMayo-type photochemistry of 1,3-dioxin-4-ones has been beautifully applied by Winkler et al. to the synthesis of complex natural products. Substrate 133 gave under sensitized irradiation (with acetone as cosolvent) product 134 as single diastereoisomer (Scheme 6.47). The diastereoselectivity results from cyclic stereocontrol exerted by the two stereogenic centers in the spiro-bis-lactone part of the starting material. After installation of the furan, saponification and bond scission in a retro-aldol fashion generated a keto carboxylic add, which produced the natural product ( )-saudin (135) by simultaneous formation of two acetal groups [128]. 

The preparation of a number of medium ring benzoic acid lactones was achieved by treatment of compounds such as VIII/176 with an excess of meta-chloroperoxybenzoic acid in dichloromethane, Scheme VIII/33 [103]. However, this oxidation reaction is not general for the synthesis of aromatic lactones. If the same reaction conditions are used as in the conversion of VIII/176 to VIII/177, the methoxy derivative VIII/178 is not transformed into the corresponding lactone. Instead the cyclic carbonate VIII/183 was isolated in a yield of 50 %. The proposed mechanism of this abnormal reaction is shown in Scheme VIII/33. From model compounds, the methoxyl group in the para-position to the center of oxidation seems to be important for the formation of VIII/183 [103]. The carbonate VIII/183 is unstable in aqueous alkaline medium and decomposes to the spiro compound, VIII/185, Scheme VIII/33 [103]. For an analogous reaction, see ref. [104]. 

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...

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