0-Diketones bicyclic

Several papers this year have been devoted to the effect of acids, notably acetic acid, on reactions between carbonyl compounds and chlorophosphines. Thus dichlorophosphines react with cyclic ketones to give the phosphinic chlorides (40), but in the presence of acetic acid the products are a-hydroxyalkyl derivatives, such as (41). When phosphorus trichloride and acetic acid are added to 1,5-diketones, bicyclic phosphonates (42) are formed the authors suggest that the reaction is... 

P-diketones, bicyclic, partially-protected 43, 981 Siloxycyclopropane ring... 

The reactions of enamines with a,/3-unsaturated acid chlorides have provided bridged bicyclic diketones 312,313). 

An interesting bridged-sulfur compound, which is a natural constituent of Iranian oil, has been synthesized 478) by the reaction of a bicyclic bis-enamine with sulfur dichloride and subsequent Wolff-Kishner reduction of an initial sulfur-bridged diketone. Sulfur dichloride has also been added to a number of vinylogous amides 479). 

In addition to the intermolecular Paterno-Buchi reaction, the intramolecular variant has also been studied the latter allows for the construction of bicyclic structures in one step. For example the diketone 8 reacts quantitatively to the bicyclic ketone 9 ... 

The reaction of a cyclic ketone—e.g. cyclohexanone 1—with methyl vinyl ketone 2 resulting in a ring closure to yield a bicyclic a ,/3-unsaturated ketone 4, is called the Robinson annulation This reaction has found wide application in the synthesis of terpenes, and especially of steroids. Mechanistically the Robinson annulation consists of two consecutive reactions, a Michael addition followed by an Aldol reaction. Initially, upon treatment with a base, the cyclic ketone 1 is deprotonated to give an enolate, which undergoes a conjugate addition to the methyl vinyl ketone, i.e. a Michael addition, to give a 1,5-diketone 3 ... 

The condensation of dihydrazones of aryl-substituted 1,2-diketones with aryl-substituted 1,2-diketones has also been described, albeit with rather low yields (up to 15 %).20 Subsequently, it was explicitly shown that this reaction leads to the same products as the dimerization of benzil monohydrazones, i.e. the 1,2,5,6-tetrazocine system, is not produced, rather the bicyclic tetraazapentalene system is obtained,21... 

In a recent total synthesis of the novel neurotrophic agent merrilactone A (22, Scheme 4) by Inoue and Hirama [24], key intermediate 21 with the cis-bicyclo[3.3.0] octane framework embedded within the caged pentacycle 22 was elaborated from cyclobutane 18 by a sequence of RCM and immediate cleavage of the resulting bicyclic vicinal diol 19 to raeso-diketone 20. Cyclooctenedione 20 then underwent regioselective transannular aldol reaction at low temperature (LHMDS, THF, -100 °C) to produce a 3 1 mixture of isomers in 85% combined yield. The major isomer 21 with the required stereochemistry was then converted into the racemic natural compound ( )-22 in 19 steps. 

An interesting combination of enzymatic with non-enzymatic transformation in a one-pot three-step multiple sequence was reported by Waldmann and coworkers [82]. Phenols 125 in the presence of oxygen and enzyme tyrosinase are hydroxylated to catechols 126 which are then oxidized in situ to ortho quinones 127. These intermediates subsequently undergo a Diels-Alder reaction with inverse electron demand by reaction with different dienophiles (Table 4.19) to give endo bicyclic 1,2-diketones 128 and 129 in good yields. 

By complexation of the rac-bicyclic diketone (rac-133) with 10a, R)- -)-l33 was included enantioselectively to give a 1 1 complex of 10a and enantiomerically pure R)-(-)-133. Treatment of the complex with NaBH4 in the solid state gave R,R)- -)-l34 of 100% ee in 54% yield [28]. Not only enantioselective but also regioselective reduction of the cyclopentanone moiety of 133 occurred. X-ray... 

Grogan G, GA Roberts, D Bougioukou, NJ Turner, SL Flitsch (2001) The desymmetrization of bicyclic P-diketones by an enzymatic retro-claisen reaction. J Biol Chem 276 12565-12572. 

CHEC-II(1996) comprehensively outlines the most commonly used synthetic approaches applied to these types of bicyclic compounds of phosphorus, arsenic, antimony, and bismuth <1996CHEC-II(8)863>. The six classes of compounds listed in this section have received considerable attention over the review period and as such the principal synthetic methods for these compounds are discussed. Schoth et al. <2000CCR101> have reviewed the use of fluorinated 1,3-diketones, 2-trifluoroacetylphenols, and their derivatives in the synthesis of phosphorus compounds. Included in this review is the use of these reagents for the synthesis of various [3.3.1] nonfused and [3.3.0] fused phosphorus bridgehead bicyclic systems. 

With a synthesis of 58 completed, the key intramolecular diketone aldol cyclization was investigated. Precedent for this type of 1,8-dicarbonyl aldol reaction is rare, although an aldol reaction has been proposed in the biosynthetic pathway to the hypocrellins. The only reported examples of such diketone aldol cyclizations involve multicyclic or bridged bicyclic systems, and of these no examples exist for 1,8-diketones forming 7-membered rings. MM2 calculations indicated that a... 

In contrast to the above general scheme (p. 66), the strained bicyclic cyclopro-penone 4047 is attacked by hydroxide ion at both three-ring sites (C3 and C1 2 ) resulting in formation of acid 320 and 1,2-diketone 321 in a ratio of 2 3,... 

A range of symmetrical bicyclic /3-diketones can be converted to 2,3-disubstituted cycloalkanones in high yield with high diastereomeric and enantiomeric excess using a cell-free preparation of a retro-Claisenase enzyme, or /3-diketone hydrolase, the gene for which has been heterologously expressed in Escherichia coli. ... 

A synthetic method for the preparation of the diketone substrates has been presented HiU, C.L., McGrath, M., Hunt, T. and Grogan, G., A generic and reproducible route to homo- and heteroannular bicyclic /3-drketones via Knochel-type 1,4-conjugate additions to o ,/ -unsaturated cycloalkenones. Synlett, 2006, 309. 

The present procedure is simpler than others previously described and gives equally good yields. It is easily adapted to the preparation of large quantities of either the diester or the diketone. It can be extended to the preparation of various alkylated 1,4-cyclohexanediones and bicyclic diketbdicarboxylic esters such as diethyl bicyclo[2.2.2]octane-2,5-dione-l,4-dicar-boxylate. 1,4-Cyclohexanedione is a useful intermediate for... 

The ketone 73 was reduced chemo- and diastereoselectively and protected to provide the silyl ether 74. The ester function was then deprotonated to the corresponding ester enolate (75) that was alkylated with methyl iodide exclusively from the Re face of the enolate to afford the bicycle 76 (Scheme 11). The substrate for the retro-aldol reaction (77) was prepared by a sequence that consists of seven functional and protecting group transformations. The retro-aldol reaction converted the bicyclic yS-hydroxy ketone 77 into the 1,3-diketone 69 via the alkoxide (78) in very good yield. 

The first successful synthesis of longifolene was described in detail by E. J. Corey and co-workers in 1964. Scheme 13.19 presents a retrosynthetic analysis corresponding to this route. A key disconnection is made on going from I => II. This transformation simplifies the tricyclic skeleton to a bicyclic one. For this disconnection to correspond to a reasonable synthetic step, the functionality in the intermediate to be cyclized must engender mutual reactivity between C-7 and C-10. This is achieved in diketone II, because an enolate generated by deprotonation at C-10 can undergo an intramolecular Michael addition to C-... 

Modest yields of bicyclic 1,2,4-trithiolanes (156) have been obtained from the sulfurization of nonenolizable diketones of type (157) using Lawesson s reagent (Scheme 44) <90JOC2421>. Although the reaction is limited, a similar procedure has provided one of the few routes to 1,3,4-oxadithiolanes (158) from the corresponding keto hydrazone (159) (Scheme 44) <92CC7,93BCJ1714>. 

Oxidation of 2,3-epoxynorbomane to diol, ketohydroxy, and diketone derivatives was studied with RuCyaq. oxidant/CCl -CHjCN (co-oxidant=(I04) , H O, Oxone , (CIO)", (S Og) " (BrO )" was ineffectual) [73]. The system RuClj/aq. Na(10 )/CCl4-CH3CN oxidised substituted epoxides containing bicyclic [2.2.1] heptane skeletons, e.g. exo-2,3-epoxynorbomanes to the corresponding diketo compounds [74]. Stoicheiometric RuOyCCl converted 20,21-dihydroxy-lip,... 

Bis C-alkylation is observed using Al,Al-disubstituted enamines of cycloaUca-nones and leads to the bicyclic p-diketones 578 (Scheme 7.183). ... 

Other removal procedures include reaction of the bicyclic lactam 4 with hydride (R6 = H) or an alkyl metal (R6 = alkyl). After hydrolysis of the bicyclic azahemiketal 5, ketoaldehydes or diketones 6 result. These can then be used in intramolecular aldol-type reactions to furnish enantiomerically pure cyclopentenones 7 (n = 1). The same reaction sequence can be used to prepare cyclohexenones (see Table 9)3-6 7l 1 ... 

Bicyclic diketone 48 (R = H, n = 2) was recently cyclized to 65% of dihydroxy derivative 61, which yielded 84% of 62 on treatment with catalytic traces of HC1.106... 

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