Cyclohexenones 4-hydroxy

Further functionalized compounds, such as 4-hydroxy-2-cyclohexenones, were found to be very useful substrates for both allylsilane, and alkynylsilane cyclizations. More importantly, these cyclizations can be run in high chemical yields under mild acid catalysis. 

A related cyclization can be realized starting from 4-hydroxy-2-cyclohexenones 13 or the corresponding protected ketal 12. The reaction can be initiated either by Bronsted or by Lewis acids. The stereochemical outcome is dependent on the Lewis acid used47-58,59. 

Diastereoselective reduction of chiral fl-keto sulfoxides1 (13, 115-116). This reaction, which can be controlled to provide either diastereomer of a chiral P hydroxy sulfoxide, has been used to obtain (R)- or (S)-4-hydroxy-2-cyclohexenones from the monoketal (2) of 1,4-cyclohexanedione. Sulfinylation of 2 with (S)-( —)-... 

Ohnemuller, UK, Nising, CF, Encinas A, Erase S (2007) A Versatile Access to Enantiomerically Pure 5-Substituted 4-Hydroxy-2-cyclohexenones. An Advanced Hemisecalonic Acid A Model. Synthesis 2175... 

The authors proposed the mechanism depicted in Scheme 5.30a to explain the stereoselective synthesis of these 4-hydroxy-2-cyclohexenones 49. This mechanistic pathway... 

J. Barluenga, M. G. Suero, R. De la Campa, J. F16rez, Angew. Chem. Lnt. Ed 2010,49,9720-9724. Enantioselective synthesis of 4-hydroxy-2-cyclohexenones through a multicomponent cyclization. 

Nising CF, Ohnemuller UK, Brase S (2006) A Short and Practical Access to Both Enantiomers of 4-Hydroxy-cyclohexenone Based on a Desymmetrizing CBS Reduction. Synthesis 2643... 

Photoirradiation of both neat and benzene solutions of 2-cyclohexenone (66b) gives a complex mixture of photodimers [40]. However, photoirradiation of a 1 1 complex of 66b with the chiral host (S,S)-(-)-l,4-bis[3-(o-chlorophenyl)-3-hydroxy-3-phenylprop-l-ynyl]benzene (167) in the solid state (Scheme 24) gave (-)-anf/-head-to-head dimer 168 of 46% ee in 75% yield [40]. This reaction was found to proceed in a single crystal-to-single crystal manner. The mechanism of the reaction was studied by X-ray crystal structural analysis [41]. 

Ring enlargement.1 A new route to seven-membered ring systems from a cyclohexenone (1) involves a photocycloaddition of ethylene to provide the bicy-clooctanone 2. Addition of lithio-1,3-dithiane to 2 provides the adduct 3, which on reaction with HgO and HBF4 forms an unstable rearranged hydroxy aldehyde... 

In 1999, Sanjuan and co-workers [27] reported a very elegant type IIavRH oxidation of cyclohexene to give a mixture of cyclohexane-1, 2-diol, 2-cyclohexenol, and 2-cyclohexenone. The reaction is initiated by excitation of the zeolite-embedded 2,4,6-triphenylpyrylium cation to produce a hydroxy radical (steps 1 and 2... 

The asymmetric addition of thiolates to 2-cyclohexenone was induced in an inter-molecular induction process by catalytic amounts of the 4-hydroxy-(S)-proline derivative (236) 235>. 

They can be prepared from acyclic compounds. In an industrial process, dimethyl malonate is condensed with 4-alken-3-ones (or a mixture of the respective ketones with 5-chloroalkan-3-ones) to give a substituted 3-hydroxy-2-cyclohexenone. Aromatization, in good yield is achieved by reaction of the hydroxycyclohexenones... 

A similar reaction with aldehydes results in y-hydroxy-a,/i-unsalurated acids (66% yield, 1 example). The anion 2 undergoes exclusive 1,4-addition to cyclopentenone and cyclohexenone (yields of products, 67% and 85%, respectively). The anion thus is the equivalent of a -carboxyl vinyl anion. 

Control over the absolute configuration in cyclohexenone photocycloadditions has been achieved by auxiliary-induced diastereoselectivity. In particular, esters related to compound 26, which are derived from a chiral alcohol but not from methanol, lend themselves as potential precursors, from which the chiral auxiliary can be effectively cleaved [42, 43]. In a recent study, the use of additives was advertised to increase the diastereomeric excess in these reactions [44], An intriguing auxiliary-induced approach was presented by Piva et al., who employed chiral 13-hydroxy-carboxylic adds as tethers to control both the regioselectivity and the diastereoselectivity of intramolecular [2 + 2]-photocycloaddition reactions [45]. In Scheme 6.14 the reaction of the (S)-mandelic acid derived substrate 38 is depicted, which led with very good stereocontrol almost exclusively to product 39a, with the other diastereoisomer 39b being formed only in minor quantities (39a/39b = 96/4). Other acids, such as (S)-lactic acid, performed equally well. The chiral tether could be cleaved under basic conditions to afford enantiomerically pure cydobutane lactones in good yields. 

Epothilone A (2) is a natural product that exhibits taxoterelike anticancer activity. A new synthesis of the ketoacid 6, a common C1-C6 fragment used in the total synthesis of epothilone A, was accomplished by directed aldol reaction of acetone with the aldehyde 34 (Scheme 2.3c). The aldol reaction of acetone with the aldehyde 3 in the presence of D-proline proceeded smoothly to furnish the expected aldol product (4) in 75% yield and with greater than 99% ee. Intramolecular aldol reaction of the hydroxy ketone 4 in the presence of pyrrolidine gave the cyclohexenone 5 in good yield. Protection of the alcohol as a TBS ether followed by oxidation of the alkene then produced the desired ketoacid (6). 

Secondary and tertiary TV-alkylamino-cyclohexenones and -cyclopentenones react quite differently with quinones. Partially reduced dibenzooxazinone can be obtained in low yield by reaction of 2,5-dichloro-l,4-benzoquinone and a secondary ketoenamine as a consequence of [4 + 2]-heterocyclization. Tertiary enaminones, however, yield hydroxy cyclohexa- and cyclohepta-benzofuranones by a polar reaction in good yield after splitting the amine moiety316 (equation 234). 

Photohydration of 3-oxo-A -compounds in water-methanol (4 1) gave the corresponding 5a-hydroxy-3-oxo-compounds. ° Photolysis of 3-oxo-4-tosyl-oxycholest-4-ene (204) gave the hydroxy-compound (205) whereas the simple cyclohexenone derivatives (206) afforded the 3-aryl-2-hydroxycyclohexenones (207). It was established that photo-Beckmann rearrangement of A-nor-5a-cholestan-3-one oxime proceeded with retention of configuration at C-5. 

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