Potassium enones

Cydopentane reagents used in synthesis are usually derived from cyclopentanone (R.A. Ellison, 1973). Classically they are made by base-catalyzed intramolecular aldol or ester condensations (see also p. 55). An important example is 2-methylcydopentane-l,3-dione. It is synthesized by intramolecular acylation of diethyl propionylsucdnate dianion followed by saponification and decarboxylation. This cyclization only worked with potassium t-butoxide in boiling xylene (R. Bucourt, 1965). Faster routes to this diketone start with succinic acid or its anhydride. A Friedel-Crafts acylation with 2-acetoxy-2-butene in nitrobenzene or with pro-pionyl chloride in nitromethane leads to acylated adducts, which are deacylated in aqueous acids (V.J. Grenda, 1967 L.E. Schick, 1969). A new promising route to substituted cyclopent-2-enones makes use of intermediate 5-nitro-l,3-diones (D. Seebach, 1977). 

Triethylammonium formate is another reducing agent for q, /3-unsaturated carbonyl compounds. Pd on carbon is better catalyst than Pd-phosphine complex, and citral (49) is reduced to citronellal (50) smoothly[55]. However, the trisubstituted butenolide 60 is reduced to the saturated lactone with potassium formate using Pd(OAc)2. Triethylammonium formate is not effective. Enones are also reduced with potassium formate[56]. Sodium hypophosphite (61) is used for the reduction of double bonds catalyzed by Pd on charcoal[57]. 

If the equilibrium were established rapidly, reduction of the free ketone as it formed would result in a substantial loss of product. Lithium enolates are more covalent in character than are those of sodium and potassium and consequently are the least basic of the group. This lower thermodynamic basicity appears to be paralleled by a lower kinetic basicity several workers have shown that lithium enolates are weaker bases in the kinetic sense than are those of sodium and potassium." As noted earlier, conjugated enones... 

The 17a-ethynyl compound (59) has been prepared in 88% yield from estr-4-ene-3,17-dione (58) and acetylene, at 2-3 atm pressure in tetrahydro-furan in the presence of potassium t-butoxide. Presumably the A-ring enone system is protected as the enolate anion during the course of the reaction. 

In the third sequence, the diastereomer with a /i-epoxide at the C2-C3 site was targeted (compound 1, Scheme 6). As we have seen, intermediate 11 is not a viable starting substrate to achieve this objective because it rests comfortably in a conformation that enforces a peripheral attack by an oxidant to give the undesired C2-C3 epoxide (Scheme 4). If, on the other hand, the exocyclic methylene at C-5 was to be introduced before the oxidation reaction, then given the known preference for an s-trans diene conformation, conformer 18a (Scheme 6) would be more populated at equilibrium. The A2 3 olefin diastereoface that is interior and hindered in the context of 18b is exterior and accessible in 18a. Subjection of intermediate 11 to the established three-step olefination sequence gives intermediate 18 in 54% overall yield. On the basis of the rationale put forth above, 18 should exist mainly in conformation 18a. Selective epoxidation of the C2-C3 enone double bond with potassium tm-butylperoxide furnishes a 4 1 mixture of diastereomeric epoxides favoring the desired isomer 19 19 arises from a peripheral attack on the enone double bond by er/-butylper-oxide, and it is easily purified by crystallization. A second peripheral attack on the ketone function of 19 by dimethylsulfonium methylide gives intermediate 20 exclusively, in a yield of 69%. 

On the basis of precedent established previously by Still,9 the C2-C3 enone double bond in 18 is stereoselectively oxidized with potassium terf-butylperoxide to give a 4 1 mixture of stereoiso-... 

The hydrogeh atom bound to the amide nitrogen in 15 is rather acidic and it can be easily removed as a proton in the presence of some competent base. Naturally, such an event would afford a delocalized anion, a nucleophilic species, which could attack the proximal epoxide at position 16 in an intramolecular fashion to give the desired azabicyclo[3.2.1]octanol framework. In the event, when a solution of 15 in benzene is treated with sodium hydride at 100 °C, the processes just outlined do in fact take place and intermediate 14 is obtained after hydrolytic cleavage of the trifluoroacetyl group with potassium hydroxide. The formation of azabi-cyclo[3.2.1]octanol 14 in an overall yield of 43% from enone 16 underscores the efficiency of Overman s route to this heavily functionalized bicycle. 

The diastereoselective intramolecular Michael addition of /(-substituted cyclohexcnoncs results in an attractive route to ra-octahydro-6//-indcn-6-ones. The stereogenic center in the -/-position of the enone dictates the face selectivity, whereas the trans selectivity at Cl, C7a is the result of an 6-exo-trig cyclization. c7.v-Octahydro-5//-inden-5-ones are formed as the sole product regardless of which base is used, e.g., potassium carbonate in ethanol or sodium hydride in THF, under thermodynamically controlled conditions139 14°. An application is found in the synthesis of gibberellic acid141. 

Optically active y-alkoxycyclopentenones have become popular in the diastereoselective synthesis of hms-3,4-disubstituted cyclopentanones. The Michael addition to these cyclic enones catalyzed by sodium ethoxide in ethanol277 or by potassium tm-butoxide278 279 proceeds under kinetic control trans with respect to the y-substituent. 

The optimal reaction conditions were applied with 59d in the addition of various aryl boronic acids and potassium trifluoroborates to several cyclic and acyclic enones (Fig. 8). Arylboronic acids added to cyclic enones in high yields (89-97%) and with good to excellent selectivities (85-98% ee). Under these conditions, the potassium trifluoroborate reagents reacted at faster rates, but with slightly lower selectivities (83-96% ee). The reactions of acyclic enones with aryl boron reagents gave also excellent yields (83-96%). 

Addition of RJCuLi to bridgehead enones.1 Ordinarily organocuprates do not react with a bridgehead halide. However, they can undergo conjugate addition to bridgehead enones generated in situ from p-bromo ketones with potassium t-butoxide or lithium 2,6-di-r-butyl-4-methylphenoxide (6,95). 

Cyanide ion acts as a carbon nucleophile in the conjugate addition reaction. An alcoholic solution of potassium or sodium cyanide is suitable for simple enones. 

Reaction at the C atom of nitronate salts is known with a variety of electrophiles, such as aldehydes (Henry reaction) and epoxides (191-193). Thus the incorporation of the nitro moiety and the cyclization event can be combined into a tandem sequence. Addition of the potassium salt of dinitromethane to an a-haloaldehyde affords a nitro aldol product that can then undergo intramolecular O-alkylation to provide the cyclic nitronate (208, Eq. 2.17) (59). This process also has been expanded to a-nitroacetates and unfunctionalized nitroalkanes. Other electrophiles include functionalized a-haloaldehydes (194,195), a-epoxyaldehydes (196), a-haloenones (60), and a-halosulfonium salts (197), (Chart 2.2). In the case of unsubstituted enones, it is reported that the intermediate nitronate salt can undergo formation of a hemiacetal, which can be acetylated in moderate yield (198). 

The related dirhodium(II) a-caprolactamate (cap) complex [Rh2(p--cap)4] undergoes a one-electron oxidation process at quite a lower potential (11 mV) than the acetate complex (1170 mV). In agreement with the Kochi hypothesis, the a-caprolactamate complex has recently been found to be an exceptional catalyst for the allylic oxidation of alkenes under mild conditions. A wide range of cyclohexenes, cycloheptenes, and 2-cycloheptenone (Eq. 5) are rapidly converted to enones and enediones in 1 h with only 0.1 mol % of [Rh2( x-cap)4] and yields ranging from 60 to 90%, in the presence of potassium carbonate [34]. 

Reaction of that with potassium tert-butoxide affords the corresponding carbanion this is thought to first add to the enone in (5-3). The anion from the reaction with a second equivalent of base then adds to the enone function to form the spiw ring. The fact that the product from this reaction has the same relative stereochemistry as the natural product is attributed to the better overlap of the enolate with the triple bond in the transition state leading to that isomer. The product from the reaction is thus + griseo-fulvin (5-6) [5]. 

Enone 149, after treatment with bromine and then with anhydrous potassium carbonate gives unsaturated y-lactone 150 (73%). After hydrogenation of the double bond A and reaction with NaH in the presence of ethyl formiate, 151 is obtained in 91% yield. Then, the double bond A7 is regenerated and the aldehyde is protected in the form of acetal (54% yield). 

Directed introduction of fluorine has been developed on the basis of the above-mentioned observations. Ketones can be converted into ft-dioxo derivatives with ethyl formates. Thus, fluorination of enolates 12 gives the fluoro derivatives which readily decompose in the presence of potassium acetate to products 13 5 -fluorogriseofulvin (14),2 5 many fluorocyclohexanones.26 and 5-fluoro-4,4-dimethylcyclopent-2-enone (15)27 can be prepared in this way. 

The reaction of potassium dienoxy borates with A-fluorobis(phenylsulfonyl)amine (la) gives y-fluoro enones in good yield. The potassium dienoxy borates are prepared by treating potassium enolates derived from unsaturated ketones with 2-phenyl-1,3,2-benzodioxaborole. This methodology offers a convenient alternative to the traditional fluorination of dienol acetates, ethers, or enamines.145 An example is given by the formation of 13.145... 

The dibromides 45 on treatment with potassium carbonate or triethylamine are easily and regioselectively dehydrobrominated to the a-bromo-a,/J-enones 46.98... 

---