Allyl ketones, preparation

The majority of catalytic enantioselective allylation reactions involve the chiral Lewis-acid-catalysed additions of allylsilanes or allylstannanes to carbonyl compounds. Monothiobinaphthol has been used by Woodward et al. as a chiral promoter in the enantioselective catalytic allylation of aryl ketones with impure Sn(allyl)4, prepared from allyl chloride, air-oxidised magnesium and SnCl4. Therefore, the allylation of arylketones in these conditions was achieved very efficiently, since the corresponding allylic alcohols were formed in... 

Some representative Claisen rearrangements are shown in Scheme 6.14. Entry 1 illustrates the application of the Claisen rearrangement in the introduction of a substituent at the junction of two six-membered rings. Introduction of a substituent at this type of position is frequently necessary in the synthesis of steroids and terpenes. In Entry 2, formation and rearrangement of a 2-propenyl ether leads to formation of a methyl ketone. Entry 3 illustrates the use of 3-methoxyisoprene to form the allylic ether. The rearrangement of this type of ether leads to introduction of isoprene structural units into the reaction product. Entry 4 involves an allylic ether prepared by O-alkylation of a (3-keto enolate. Entry 5 was used in the course of synthesis of a diterpene lactone. Entry 6 is a case in which PdCl2 catalyzes both the formation and rearrangement of the reactant. 

Substituted 2-(/J-oxoalkyl)tetrahydrofurans have been prepared in acceptable yields by a one-step aldol-type reaction of allyl ketones and 4-methyl-l-phenyl-4-penten-l-one, catalyzed by a rhodium(I) complex-tin(II) chloride mixture (equation 180)652. This type of catalyst mixture has also been used for both linear653 and cyclic654 codimers in a similar fashion. 

Allyl ketones can be prepared by trapping acylpalladium intermediates with main group metal compounds. The allyl ketone 251 can be prepared from the allyl ester 248 by trapping acylpalladium 249 with the alkylzinc compound 250 at room temperature and 1 atm [115]. Reaction of geranyl chloride (252) with the furylstannane 253 under CO pressure afforded the ketone 254, which was converted to dendrolasin (255) [93]. Aldehydes are prepared by trapping with a metal hydride. The /l,y-unsaturated aldehyde 257 is prepared by the carbonylation of the allyl chloride 256 in the presence of Bu3 SnH [116,117],... 

P-Alkoxy kettmes and y-acetoxy ketones prepared by the oxidation of allyl ethers and homoallyl acetates, respectively, are synthetically useful intermediates. The reaction of (K) in the presence of excess sodium methoxide with 2-methylcyclohexanone afforded methyloctalone (94) in 42% yield (equation... 

Kosugi, M., Shimizu, Y., Migita, T. Reaction of allyltin compounds. II. Facile preparation of allyl ketones via allyltins. J. Organomet. Chem. 1977, 129, C36-C38. 

Nokami reported allylation of carbonyl compounds by use of allyl halides and tin powder in the presence of water [45]. In this reaction, water obviously accelerates the addition, and the allylating reagent prepared in situ reacted with ketones... 

Allylation. 2-Allyl-l,2-oxaborolane is an allylating agent prepared from reaction of 2-allyloxy-l,2-oxaborolane with allylmagnesium bromide. Allylation is carried out without solvent, between 0°C to room temperature with aldehydes and at 80-100°C with ketones. Conjugated aldehydes undergo 1,2-addition. 

The 1,5-diketone 21 is prepared by 3-butenylation of ketones to give 20 via Pd-catalyzed hydrogenolysis of the allylic acetate 19, followed by Pd-catalyzed oxidation, and is used for annulation to form the cyclohexenone 22 [19]. In this method, the 3-butenyl group is a masked methyl vinyl ketone. Preparation of the 1,7-diketone 24 was performed by oxidation of 23, and applied to the synthesis of dysidiolide (25) [23]. 

Allyl ketones are prepared by cross-coupling of allyl esters with acyl metals. For the coupling, allyl trifluoroacetate (306) and the acylstannane 307 were used to provide the ketone 308 [112]. Similarly, acylsilanes such as 310 are used for the coupling with allyl trifluoroacetate 309 to give 311 [113]. For these couplings, use of allyl trifluoroacetate is important. No reaction occurred with allyl acetate. While ligandless palladium trifluoroacetate is most effective, Pd(OAc)2 shows low activity. 

Applications of these reactions have been reported. Wicha and co-workers prepared the allylated ketone 552 in 87 % yield as a synthetic intermediate of vitamin D by the reaction of the silyl enol ether 550 with the cw-allyl carbonate 551 [202]. 

No allylation of simple ketones, aldehydes, and esters without additional EWGs occurs. Allylation of ketones is carried out indirectly. For example, enamines, prepared from ketones, are allylated easily and allyl ketones are obtained after hydrolysis (Scheme... 

The oxygenation of the allylic ketones. Direct evidence for such type of lipoxygenase reaction was obtained in 1991 independently by ourselves [4] and by German group [5]. The last one incubated an allyUc ketone, prepared by oxidation of ricinoleic acid, with soybean LOX. They have identified an a,jS-unsaturated 7-diketone as the predominant product. Studying the oxidation of a-ketols, we have suggested, that the primary products of their LOX oxidation are the corresponding hydroperoxides [4]. 

Several 1,4-dicarbonyl compounds are prepared based on this oxidation. Typically, the 1,4-diketone 10 or the 1,4-keto aldehyde 12 can be prepared by the allylation of a ketone[24] or aldehyde[61,62], followed by oxidation. The reaction is a good annulation method for cyclopentenones (11 and 13). Syntheses of pentalenene[78], laurenene[67], descarboxyquadrone[79], muscone (14 R = Me)[80]) and the coriolin intermediate 15[71] have been carried out by using allyl group as the masked methyl ketone (facing page). 

Allylic carbonates are most reactive. Their carbonylation proceeds under mild conditions, namely at 50 C under 1-20 atm of CO. Facile exchange of CO2 with CO takes place[239]. The carbonylation of 2,7-octadienyl methyl carbonate (379) in MeOH affords the 3,8-nonadienoate 380 as expected, but carbonylation in AcOH produces the cyclized acid 381 and the bicyclic ketones 382 and 383 by the insertion of the internal alkene into Tr-allylpalladium before CO insertion[240] (see Section 2.11). The alkylidenesuccinate 385 is prepared in good yields by the carbonylation of the allylic carbonate 384 obtained by DABCO-mediated addition of aldehydes to acrylate. The E Z ratios are different depending on the substrates[241]. 

Ketones can be prepared by trapping (transmetallation) the acyl palladium intermediate 402 with organometallic reagents. The allylic chloride 400 is car-bonylated to give the mixed diallylic ketone 403 in the presence of allyltri-butylstannane (401) in moderate yields[256]. Alkenyl- and arylstannanes are also used for ketone synthesis from allylic chlorides[257,258]. Total syntheses of dendrolasin (404)f258] and manoalide[259] have been carried out employing this reaction. Similarly, formation of the ketone 406 takes place with the alkylzinc reagent 405[260],... 

Another preparative method for the enone 554 is the reaction of the enol acetate 553 with allyl methyl carbonate using a bimetallic catalyst of Pd and Tin methoxide[354,358]. The enone formation is competitive with the allylation reaction (see Section 2.4.1). MeCN as a solvent and a low Pd to ligand ratio favor enone formation. Two regioisomeric steroidal dienones, 558 and 559, are prepared regioselectively from the respective dienol acetates 556 and 557 formed from the steroidal a, /3-unsaturated ketone 555. Enone formation from both silyl enol ethers and enol acetates proceeds via 7r-allylpalladium enolates as common intermediates. 

---