Spirocyclic diketones

Nair and co-workers have demonstrated NHC-catalysed formation of spirocyclic diketones 173 from a,P-unsaturated aldehydes 174 and snbstitnted dibenzylidine-cyclopentanones 175. Where chalcones and dibenzylidene cyclohexanones give only cyclopentene products (as a result of P-lactone formation then decarboxylation), cyclopentanones 175 give only the spirocychc diketone prodncts 173 [73]. Of particular note is the formation of an all-carbon quaternary centre and the excellent level of diastereoselectivity observed in the reaction. An asymmetric variant of this reaction has been demonstrated by Bode using chiral imidazolium salt 176, obtaining the desymmetrised product with good diastereo- and enantioselectivity, though in modest yield (Scheme 12.38) [74],... 

These sorts of compounds may look rather difficult to come by, but some simple ones are simply made. Cyclization of this keto-acid with polyphosphoric acid leads to a spirocyclic diketone. 

It is much more difficult to pass stereochemical information from one ring to the other in spirocyclic compounds because each ring is orthogonal to the other. Nonetheless, some reactions are surprisingly stereoselective—one such is the reduction of the spirocyclic diketone that we made a moment ago. Treatm it with 1-iAllI4 gives one diastereoisomer of the spirocyclic diol. 

Tu and co-workers [11] reported an intriguing methodology for the synthesis of spirocyclic compounds. Hydroxy enones 13 undergo semipinacol-type 1,2-carbon migration in the presence of cinchona-derived primary amines to afford spirocyclic diketones via iminium catalysis. 

As depicted in the following scheme, a homoallyl alcohol derived from a norbomyl a-diketone underwent a lead(IV) acetate reaction in MeOH, resulting in the formation of a novel methoxy substituted spirocyclic tetrahydrofuran <07CC4239>. It is believed that the addition of the methoxylead(IV) acetate species across the alkene from the less sterically hindered side to form a plumbonium cation leads to the major product after subsequent cyclization and reductive elimination. Moreover, construction of tetrahydrofurans by a Pd(II)/Pd(IV)-catalyzed aminooxygenation of homoallyl alcohols was also reported <07AGE5737>. 

In contrast to intermolecular photoaldols, which can be manipulated with facility, intramolecular cycloadducts undergo retro-[2 + 2] cycloaddition when subjected to hydrolytic conditions. In an alternative protocol, oxymercuration of (229) afforded a-mercurio ketone (230 42%) which was acetylated under standard conditions to provide 1,4-diketone (231) quantitatively. Similarly, epoxidation of (229) provided functionalized photoaldol (232), which was hydrolyzed and acetylated to form a-acetoxy derivative (233). Finally, hydrolysis of (234) (4 1 THF/0.1 N HCl) gave lactol (235) in nearly quantitative yield, illustrating the utility of the intramolecular furan carbonyl photocycloaddition in spirocycle formation. 

In a third category of cyclic 3, y-enones of synthetic potential, the chromophore moieties are linked by a spiro carbon typical examples are a 3, y-unsaturated 8-diketone and 3, y 8,e-unsaturated spirocyclic ketones. " A representative of the latter category is (53), which upon triplet sensitization with Mich-ler s ketone affords the isomers (54) and (55) in a ratio of about 2 1 and a total yield of 82% (Scheme... 

Reactions of oc-diketones and o-quinones with phosphorus compounds in the syntheses of P-heterocycles (cyclophosphates, phosphorans, spirocyclic compounds) 02CRV629. 

Herrera et al. [97,98] have reported the usage of Norrish-Yang photocyclization for the synthesis of new spirocyclic monosaccharide derivatives of types 243 and 244 via a hydrogen atom transfer (HAT) reaction promoted by a 1,2-diketone 241, in its excited state, followed by C-C tetrasubstituted bond formation in a diastereo-selective manner (Fig. 8.59). Of special interest is the study of the tendency to inversion at C5 (for examples of epimerization of anomeric and pseudoanomeric radicals, see [99, 100]), probably triggered by conformational changes that the 1,4-diradical intermediate 242 undergoes in its triplet state, within its lifetime (for discussions of the lifetime of diradicals in solution, see [101, 102]) before the intersystem crossing (ISC) occurs. 

An improved conversion of isoxazoline derivative 36 into bis-spiroketal 37, a building block used by Fiirstner et al. in the total synthesis of the methyl ester of macrolide spirastreUolide A, was reported. In particular, Mo(MeCN)3(CO)3 was found to induce N—O bond cleavage at lower temperature than Mo(CO)6 (50 vs 90 °C) and the subsequent treatment of the crude mixture with trimethylamine Af-oxide allowed the isolation of a product free of metal contaminants. Next, simultaneous removal of silyl ethers and the cyanohydrin moiety with TASF afforded an intermediate trihydroxy diketone that smoothly underwent bis-spirocyclization in the presence of a catalytic amount ofPPTS (13CEJ3596). 

The rearrangement of adducts of enol acetates derived from a-diketones has been reported. An interesting application of this principle was in a model study for the synthesis of acorenones (Scheme 14) in which the adduct (49) underwent rearrangement in base to (50) which was cleaved with lead tetra-acetate to generate the spirocyclic product (51). ... 

Additionally, in a recent report of their studies toward the related purpuromycin 64, Kozlowski and coworkers [62] found that the use of diketone 61 enabled spirocyclization to take place under acidic conditions (Scheme 16). 

The proposed mechanism for this transformation is closely related to that depicted in Scheme 40.47 above, except that the intermediate iminium ion derived from the primary amine catalyst 32 is epoxidated stereoselectively [60] and, after hydrolysis of the iminium, an acid-induced diastereoselective semipinacol rearrangement affords the spirocyclic hydroxy-diketone product (Scheme 40.53). 

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