Spirocyclic 5-lactones

The electroreductive cyclization of the furanone 118 (R = -(CH2)4CH=CH— COOMe Scheme 36) using a mercury pool cathode, a platinum anode, a saturated calomel reference electrode, and a degassed solution of dry CH3CN containing -Bu4NBr as the electrolyte, gave the spirocyclic lactones 119 and 120 in a ratio 1.0 1.1 (Scheme 37)(91T383). 

The cyclofunctionalization of cycloalkenyl systems where the chain containing the nucleophilic functionality is attached at one end of the double bond leads to spirocyclic structures. Cyclizations of cyclic and acyclic enol ethers to generate spiroacetals are shown in equations (66)168 and (67).169 These reactions generate the thermodynamically more stable products based on anomeric and steric factors.170 Spiroacetal products have also been obtained using isoxazolines as the nucleophilic functionality (cf. Table 14).l4lb Studies of steric and stereoelectronic control in selenoetherification reactions which form spirocyclic tetrahydrofurans have been reported.38 An interesting example of stereoelectronic control in the formation of a spirocyclic lactone has been reported in a recent mevinolin synthesis (equation 68).171... 

The cyclic acetal is a protected form of the hydroxy-aldehyde and oxidation under acidic conditions (Cr03 in H2S04) gives a good yield of the spirocyclic lactone. In the whole process from allyl silane to lactone, the allyl silane is behaving as a d3 synthon or homoenolate. 

Spirocyclic lactones of structures such as 100 are interesting because of potential biological activity, and might be made from available steroids such as oestrone 101. 

The same group further extended this chemistry to prepare lactones 40 and 41, and also used a modified approach towards other diacylglycerol (DAG) analogues 44 and 45. This latter approach involved synthesis of the spirocyclic lactone intermediate 43 by addition of a Grignard maganesium alkoxide to 42 and the PCC oxidation (Scheme 7). ... 

Spirocyclic lactones and the stractures derived from them are prevalent motifs in medicinal and natural product chemistry [70]. A Beckwith-Dowd ting expansion was reported for the synthesis of y-lactones 212 spirofused to 6- to 10-membered cycloalkanones (Scheme 5.46) [71]. The reaction involves a one-, three-, four-, and... 

In 2013, the Chi group developed the NHC-catalysed activation of the y-carbon atom of a-branched indole-3-carboxaldehydes to generate ortho-quinodimethane intermediates, which further reacted with trifluoromethyl ketones and isatins to give polycyclic and spirocyclic lactones 117 and 118, respectively, in good to excellent yields and over 90% enantiomeric excess (Scheme 20.50). ... 

Schmidt et al. [74] prepared spirocyclic lactones by hydroformylation-acetalization of vinyl-tetrahydropyranes followed by Ley-Griffith oxidation (Scheme 5.82). Versatile building blocks were obtained after cleavage of the lactone ring, which were suitable for the synthesis of natural compounds such as pseudomonic acid A (C-glycoside). 

The a-NeuNAc-(2->8)-a-NeuNAc(2- 3)- unit of ganglioside GDlb can form a spirocyclic lactone between the two slalosyl units in the presence of traces of acid, 47 whilst treatment of the ganglioside with DCC in DMSO gives a dilactone, the second lactone involving 0-2 of the galactose residue to which the di-sialosyl unit is attached.48... 

Interaction of ascorbic acids with a, 5-unsaturated aldehydes has led to adducts of types (43) and (44). 2 xhg diene (45), accessible in four steps from 5,6-0-isopropylidene-L-ascorbic acid, undergoes cycloaddition with various electron-rich dienes, one example being indicated in Scheme 16. The resultant (racemic) spirocyclic lactones have the skeleton and key functionality of the top half of chlorothricolide. ... 

Cao, T., Linton, E. C., Deitch, J., Berritt, S., Kozlowski, M. C. (2012). Copper(ll)-and Palladium(ll)-catalyzed enantioselective Claisen Rearrangement of allyloxy- and propargyloxy-indoles to quaternary oxindoles and spirocyclic lactones. Journal of Organic Chemistry, 77, 11034-11055. 

The tetralin-lactone framework of clyptoacetalide was assembled via cyclotri-merization of triyne intermediate 369, while the naphthalene-fused lactone core of danshenspiroketallactone, 374, was constructed via directed metallation and subsequent lactonization of the diethylamide 372. In each case, irradiation of the free alcohol in the presence of iodobenzene diacetate and iodine (i.e., Suarez oxidation conditions [185,186]) afforded the spirocyclic lactone as an inseparable mixture of the natural product and its epimer. 

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