5-Hydroxymethyl-2-cyclohexenone

The kinetic resolution of 5-hydroxymethyl-2-cyclohexenone towards the total synthesis of penienone, a fungal metabolite of Penicillium sp. no. 13 [89], has been performed by using Lipase PS from B. cepacia for the acetylation of the (S)-enantiomer, leaving the desired (/ )-alcohol. As a main problem inherent with enzymatic kinetic resolutions, the reaction yielded both products in a 1 1 mixture... 

The key step was the introduction of the hydroxymethyl group onto the a-phenylsulfonyl cyclohexenone 16 through the Michael type addition of tributylstannyl lithium followed by trapping with formaldehyde and desulfonylation. 

Tlie latter reagent undergoes 1,2-addition to a,p-unsaturated aldehydes 1,4-addition, with copper catalysis, is observed with cyclohexenone alone. A more satisfactory reagent for the conjugate introduction of the hydroxymethyl group is the allyldimethylsilylmethyl Grignt reagent... 

Hydroxymethylation. A CH OH group is introduced into C-2 of 1,4-naphthoquinones by reaction with formaldehyde in the presence of K COj and under microwave irradiation. 2-Cyclohexenones ate also hydroxymethylated at the a-position in a DMAP-catalyzed Baylis-Hillman reaction. ... 

Michael addition of the -keto-ester (429) to the vinyl cyclohexenone (430), and subsequent base-catalysed cyclisation to the key intermediate (431), has provided a route to 8)3-methoxycarbonyl-, -formyl-, and -hydroxymethyl-... 

An interesting approach to the synthesis of highly oxygenated cyclohexane derivatives has been developed by Ichihara. Benzoquinone epoxides and epox-ycyclohexenones were obtained by the thermal retro Diels-Alder reaction of epoxide 511, obtained from quinones and dimethylfulvene without isolation of the primary adduct. Intermediate 512 (R = Ac), obtained in this way from hydroxymethyl-benzoquinone, was converted into the natural compound sene-poxide (514) as shown in Scheme 6. Reductive, regioselective cleavage of the diepoxide 513 was achieved by treatment with hydrazine hydrate. The stereoselective total synthesis of crotoepoxide (515) from cyclohexenone 512 (R = Ms), and of other natural compounds with related structure, was described. ... 

In 1998, Rezgui and El Gaied were the first to carry out the DMAP-cata-lyzed MBH reaction of cyclohex-2-en-l-one derivatives 76 with formaldehyde in an aqueous medium to provide 2-(hydroxymethyl)cyclohex-2-en-l-one derivatives 77 (Scheme 2.33). They noticed that this reaction could not proceed in the presence of DABCO. p-Substituted cyclohexenone derivatives did... 

In 2009, Imagawa and Nishizawa reported the first synthesis of ( )-neovibsanin B (63) [46]. They employed an intramolecular Diels-Alder reaction of 91 at 200 °C in dimethyl imidazolidinone (DMI) as a solvent for constructing the core cyclohexenone ring of neovibsanin, leading to a mixture of 92a and 92b (9 1) in 58% yield. DMI plays a cmcial role in accelerating this reaction rate and thus makes it suitable for scale-up. Further manipulation of Diels-Alder adducts 92a and 92b involves introduction of a hydroxymethyl group by Baylis-Hillman reaction with formaldehyde to provide the key intermediate 95, Scheme 11. 

Schuster, D. 1. and Brizzolara, D. F., The mechanism of photoisomerization of cyclohexenones. 10-hydroxymethyl-A > -2-octalone the question of hydrogen abstraction from benzene by ketone triplets, /. Am. Chem. Soc., 92, 4357,1970. 

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