Cyclohexenone-3-carboxylic acid

Photocycloaddition of chiral esters of cyclohexenone-3-carboxylic acid 168 or of cyclopentenecarboxylic acid 175 led to mixtures of stereoisomeric cycloadducts with variable diastereoselection, as shown in Scheme 28 [148]. 

Allylic oxidation, for example, of cyclohexene to 2-cyclohexenone, and oxidative cleavage of styrene to benzaldehyde are readily accomplished with oxygen such reaction systems contain ALhydrox3fphthalimide and l,4-diamino-2,3-dichloro-9,10-anthraquinone. Aldehydes are converted into carboxylic acids with Pd/C, KOH and catalytic amounts of NaBH4 in the air. Very similar conditions (K2CO3 instead of KOH) are described for oxidation of benzylic and allylic alcohols. ... 

In 1991, the Danishefsky group disclosed the synthesis of the C-28-C-49 subunit of rapamycin utilizing the combination of the Perrier carbocyclization reaction and an Ireland-Claisen rearrangement (see Section 12.3.3. Scheme 12.21T The Perrier carbocyclization of 5-enopyranoside 86, prepared from 2-deoxy-d-glucose derivative (Section 12., Scheme 12.2ST followed by elimination of the p-hydro group gave cyclohexenone 152 tScheme 12.40T Luche reduction of 152 afforded cyclohexenol 83 stereoselectively. Condensation of 83 with carboxylic acid 84, prepared from (i )-3-(benzylojg )-2-methylpropanal, provided ester 82 in 75% yield. 

In conjugate reduction of enones with other transition metals such as chromium, the rates of reduction were shown to be dependent on the conformation of the substrate, with faster reactions being observed with the cisoid forms as compared with the transoid onesJ However, with the Pd/Si/Zn system, the rigid transoid enone of cyclohexenone and the flexible enone of acetylcyclohexene are both reduced in comparable rates. This indicates that palladium interacts exclusively with the olefinic part of the enone without significant participation of the carbonyl. Interestingly, this method is highly selective for unsaturated ketones and aldehydes, as the reduction of corresponding o,jS-unsaturated carboxylic acid derivatives, such as esters, amides, and nitriles, is very slow under the conditions used. Thus, ben-zylideneacetone is selectively and cleanly reduced in the presence of methyl cinnamate, dnnamonitrile, or dnnamamide.t" ... 

Table 3 Adiabatic Singlet-Triplet Splitting Energies (in kcalmol ) for the tt, n State of 2-Cyclopentcnone (2-CP), 2-Methyl-2-cycIohexenone (2-Me-CH), 3-Methyl-2-cyclohexenone (3-Me-CH) and Norbomene (Nor), and the n,. t State of 1-Cyclopentene-1-carboxylic acid (CPC). Geometries were Optimized at the HF/6-31 G(d) Level and Zero-Point Corrections are Included...

In British practice the locant (or locants) is placed immediately before the syllable that it qualifies (see p. 35), as in hexan-3-one, hexane-2,3-dione, 1-chloro-hexan-3-one, hex-3-en-l-yne, pyrazol-3-yl, carbazole-2-carboxylic acid. In USA, one locant (or one set of locants) for a suffix is placed in front of the stem name, as in 3-hexanone, 2,3-hexanedione, l-chloro-3-hexanone, 3-hexene, 3-pyrazolyl but only one numeral (or set of numerals) is so placed any others precede the syUable that they qualify, 3-hexen-l-yne, 3-cyclohexen-l-one (the 1 maybe omitted in the second name, giving 3-cyclohexenone, where the 3 refers to the unsaturation en ). There are, however, many cases where parent names carry locants in front of them, e.g., m-dioxan, 1,7-naphthyridine (where the heteroatoms in the ring are cited by the locants 1,7 or m) in such cases the additional locants for suffixes are all placed after the parent name, as in m-dioxan-4-carboxylic or l,7-naphthyridin-2(lfl )-one. The tendency in Chemical Abstracts is to place the locants after the parent name whenever ambiguity might arise it is matched by a tendency in Great Britain to place one numeral in front of the parent name when no ambiguity can arise. A compromise seems to be working itself out unofficially. 

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. 

Ficini, J. Touzin, A. M. "Cycloaddition of an ynamine to cyclohexenones. Synthesis of aminobicyclo[4.2.0]octenones Tetrahedron Lett. 1972, 2093. Ficini, J. Touzin, A. M. "Stereochemical control of an asymmetric center formed a to the carboxyl function by hydrolysis of bicyclic en amines. Stereoselective synthesis of diastereoisomericy-keto acids" Tetrahedron Lett. 1972, 2097. Ficini, J. d Angelo, J. Noire, J. "Stereospecific Synthesis of c//-Juvabione" J. 

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