Spiro -2 ,4 -diones

One of the most usefijl biocatalysts is the baker s yeast. It has been widely used to synthesize chiral intermediates. For example, baker s yeast reduction of diketones proceeds highly regio- and enantioselectively with ahphatic diketones, 2,2-disubstituted cycloalkanediones and spiro diones, producing enantiomericaUy enriched hydroxyketones (Fig. 10.7). Starting from a chiral hydroxyketone, many terpenes have been enantioselectively synthesized by Mori et at, as shown in Fig. 10.7(a). ... 

Related to the ladder polymers are the spiro polymers as typified by the reaction product of cyclo-octadecane-1, 10-dione with pentaerythritol Figure 29.22). 

Reaction of 5n,6,7,8,9,l l-hexahydropyrido[2,l-f ][l,3]benzothiazine-7,l 1-dione (47, X = S, R = H) and 2-amino-6-fluorobenzamidine dihydrochloride in boiling EtOH yielded a diastereomeric mixture of spiro derivatives 48 (X = S, R = H), which were separated by flash column chromatography (OOMIPl). 

Spiro[4.5]decane-l,4-dione and Ethyl 4-Cyclohexyl-4-oxobutanoate... 

In order to smdy the effect of perturbation arising from spiro-conjugation on the chemical reactivities, in particular the facial selectivities, sterically unbiased dienes (96 and 97) based on fluorenes in spiro geometry have been synthesized [165]. These dienes react as Diels-Alder dienes with several dienophiles (maleic anhydride (MA), A-phenylmaleimide (PMI), A-phenyl-l,3,5-triazoUne-2,4-dione (PTD) and iV-methyl-l,3,5-triazoline-2,4-dione (MTD)). 

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]. 

Because of its great reactivity PTAD has found wide use in the interception of reactive, unstable dienes. For example, unstable isoindenes,226 3a//-indenes,146 1,3-divinylallenes,227 and benzene oxides228 have all been successfully trapped with PTAD. 4-(4-Bromophenyl)-l,2,4-triazole-3,5-dione (5, R = 4-Br—C6H4) is often used if the derivatives ai e required for X-ray structure determination.229 Azodicarboxylic esters have been used to trap tetra(trifluoromethyl)cyclobutadiene,230 and spiro[4.4]nonatetraene.231... 

Also in 2001, Azizian described a one-pot diastereoselective synthesis of 2-sub-stituted l,l,2,3,3aa,3b) ,4,5,6,8,8aa-decahydro-8-(spiro-3-indolino-2-one)pyrrolo[3,4-b] pyrrolizine-l,3-dione (151) in good yield and diastereomeric excess using microwave irradiation (Scheme 9.46). 

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... 

In principle, the approach outlined above for the a-oxoamides can be applied to any reaction, ground or excited state, which converts an achiral reactant into a chiral product, and Toda, Tanaka, and coworkers have investigated a wide variety of such processes [ 15,16]. A complete discussion of their work is beyond the scope of this review, and we illustrate the general approach taken with one final example. As shown in Scheme 4, irradiation of crystalline complexes of ene-diones 20a-f with chiral host (R,R)-(-)-9b led to cyclized products 21a-f in the variable yields and ee values indicated in Table 1 [22]. Remarkably, for reasons that were not clear (there was no accompanying X-ray crystallography), the R=n-propyl derivative 20g was found to give a completely different photoproduct, spiro compound 22 (69% yield, 97% ee, stereochemistry unknown), a result that once again illustrates the rather capricious nature of the use of chiral hosts for asymmetric induction. 

The vast majority of compounds having the bisindole nucleus characteristic of the vinca structure with antitumor activity in experimental tumor systems bear a carboxyl function and a free tertiary hydroxyl group at C-3 of the vindoline moiety. The group of semisynthetic derivatives distinguished by the presence of a C-3 spiro-fused oxazolidine-l,3-dione are important exceptions to this generalization. 

Nair and co-workers reported the diastereoselective synthesis of spiro y-butyro-lactones from 1,2-dicarbonyls [125]. The authors studied the reaction with 1,2-cyclohexane dione 230 which produces the desired lactone 232 in good yields Eq. 22a. Isatins 233 are more reactive, but the products 235 are obtained as a 1 1 separable mixture of diastereomers Eq. 22b. The Nair research group extended this methodology to include homoenolate addition to tropanone 236 to form bicyclic 5-lactones 238 Eq. 22c [126]. 

In the benzyl-substituted spiro compound 30 (Scheme 18), the phenyl ring (due to a weak intramolecular interaction) was folded over the 1,3-dioxan-3,6-dione moiety (78M1263) the ABMNX spin system in the H NMR spectrum therefore was analyzed in detail (in CDCI3). 

Structure of 1,3-dimethyl-3",4 -diphenylimidazolidine-2-spiro-2 (2 jff) thiete-4,5-dione. ... 

Ring closure at the uracil 6-position also occurred with brominated aromatic derivatives 444 linked to the 6-position, to give benzopyrano[4,3-rf pyrimidine-2,4-dione spiro derivatives 445 <2004S1864>. 

Intramolecular [2 + 2] photocycloadditions have been used successfully for the syntheses of (polycyclic) cage compounds. Recent examples of such reactions are the formation of pentacyclo[5.4.0.02 6.031°.05 9]undecane-8,ll-dione-4-spiro-l-cyclopentane,55 hexacy-clo[7.4.2.01,9.03,7.04 14.061s]pentadeca-10,12-diene-2,8-dione-5-spiro-l -cyclopropane,56 pen-tacyclo[5.4.0.02 6.031°.04 8]undecane57 and pentacyclo[6.4.0.02 7.03 12.06 9Jdodeca-4,10-diene.58 Irradiation of benzoquinone tetrahydropentalene adducts afford cage compounds which are easily converted to angular tetraquinanes.59... 

Another interesting synthesis of spiro[2.3]hexan-4-one (16) comprised of dipolar attack of 4-phenyl-l,2-dihydro-4//-l,2,4-triazole-3,5-dione on bicyclopropylidcnc to give a zwitterion 17, which underwent ring enlargement to 18 before ring closure to diaziridine 19 took place. Accordingly, in the presence of water, 18 was trapped with formation of spiro[2.3]hexan-4-one (16) which was also obtained from 19 by saponification.118... 

Initial thermal sigmatropic 1,5-carbon shifts are believed to account for the product formation from spiro[2.4]hepta-4,6-diene (l) 200 and spiro[cyclopropyl-l, 2 -2 //-indene] (6),201 obtained by photodecarbonylation of dione 5. In the first case, a 1,5-hydrogen shift and an electrocyclic ring opening completes the formation of 3,4-dimethylenecyclopent-l-ene (4),200 and in the second case, the initially formed benzoannulated bicyclo[3.2.0]hepta-l,3-diene 7 dimerizes to 8 as mixture of two stereoisomers.201... 

Nearly all examples of epoxidation of alkylidenecyclobutanes involve 3-chloroperoxybenzoic acid.15 58-70 This is because the conditions are mild, the workup is easy and few byproducts are formed. Generally, dichloromethane or chloroform is used as solvent. Solid sodium hydrogen carbonate is occasionally added to avoid acid-catalyzed rearrangement of the spiro compound. For example, 6-isopropylidene-l,4,4-trimethylbicyclo[3.2.0]heptan-3-one reacted with 3-chloroperoxybenzoic acid and sodium hydrogen carbonate to give 2,2,3, 3, 6-pentamethyl-spiro[3-oxabicyclo[4.2.0]octane-8,2 -oxirane]-4-one (4) in quantitative yield. However, without the use of sodium hydrogen carbonate, substantial amounts of 2,2,6,9,9-pentamethyl-3-oxa-bicyclo[4.3.0]nonane-4,8-dione (5) and 2,2,6,8,8-pentamethyl-3-oxabicyclo[4.3.0]nonane-4,9-dione (6) were also formed.15-64... 

Another simplified nomenclature adopted here relates to natural spiro-2,3-dihydrobenzofuran derivatives, such as griseofulvin. The fundamental heterocycle, named grisan, being spirobenzofuran-2(3ff)-l -cyclohexane (5), griseofulvin (7-chloro-4,6,2 -trimethoxy-6 -methyl-spirobenzofuran-2(3//)-l -[2]cyclohexene-3,4 -dione) (6) becomes 7-chloro-4,6,2 -trimethoxy-6 -methyl-2 -grisene-3,4 -dione. 

The photoconversion of spiro[benzofuran-2,r-cyclohexa-3, 5 -diene]-2, 3(2//)-diones to dibenzofurans is recorded (81JCS(Pi)870). It was proposed that excitation of the dienone chromophore of the grisedienone (401) causes either concerted or radical ring opening to pairs of stereoisomeric dienylketenes. One member of each pair can undergo a thermal intramolecular va + tts cyclization to yield a /3-lactone subsequent loss of C02 would yield the products. 

Reaction of pyrido[2,l-6][l,3]thiazine-2,4-dione (105) with p-tosyl azide in the presence of triethylamine in acetonitrile at 0°C gave a 3-diazo derivative (106), which reacted with cyclohexene in the presence of a catalytic amount of rhodium acetate under reflux to yield a spiro derivative (107) [94H(39)219 95H(41)1631]. 

When two equivalents of an isocyanate are treated with one equivalent of an enamine, a l,3,5-triazine-2,4-dione is formed. The novel spiro compound (171) may be prepared by this route. The spiro derivative is isomerized on heating (69CB931). 

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