2- cyclohex-2-enon

Cyclic a,) -unsaturated ketones present a rich array of photochemical reactions, some of which are of considerable synthetic value (see Section 6.4 of Part B). For cyclohex-enones, two prominent reactions are the di-rr-methane rearrangement (path A) and the lumiketone rearrangement (path B). 

Tridachiahydropyrone belongs to the family of marine polypropionates [69]. Efforts towards its total synthesis have recently led to a revision of the structure with the new proposal 2-147 [70]. The construction of the highly substituted cyclohex-enone moiety 2-146 which could be incorporated into this natural product [71] has been described by Perkins and coworkers (Scheme 2.33) [70, 72]. The conjugate addition/ Dieckmann-type cydization utilizing organocopper species as Michael donors afforded the enantiopure 2-145 in 68% yield. A further methylation of the (3-ketoester moiety in 2-145 followed by an elimination led to the desired cydohex-enone 2-146. 

Cyclohexenol <1%, cyclohexenone 4%, d5/fran5-l,2-cyclohexanediols 24% [the structures of the cyclohexenol and cyclohex enone are not given]. 

The optically active 1,4-cyclohexenediol monoacetate 525, prepared by hydrolysis of the /we.so-diacetate with lipase, was converted into the optically pure cyclohex enone 526 by an elimination reaction in the presence of ammonium formate. Optically active carvone (527) was prepared from 526[343]. 

Starting from optically active 1-chlorovinyl p-tolyl sulfoxide derived from 2-cyclohex-enone, the asymmetric synthesis of cyclopropane derivative (85) was realized (equation 23) . Addition reaction of lithium enolate of tert-butyl acetate to 83 gave the adduct (84) in 96% yield with over 99% ee. Treatment of the latter with i-PrMgCl in a similar way as described above afforded optically pure (15,6/ )-bicyclo[4.1.0]hept-2-ene (85) in 90% yield. 

Soeda et al. (358) used Pd-supported heteropoly compounds for a heterogeneous Wacker-type reaction and found that Pd/Cs2 5H0 5PW6Mo6C)4o was active for oxidation of cyclohexene to produce cyclohexanone and cyclohex-enone. The active sites are assumed to be Pd2+ and Pd° for the two products, respectively. Homogeneous Wacker-type reactions are described in Section XI. 

Formation of cyclohexadiene 173 by protonation is a useful reaction. Cyclohex-enone can be prepared from anisole by this reaction. Meta-substitution of the... 

Regeneratable polymeric organotin dihydride beads have been used to reduce halides selectively (e.g. 3-bromocamphor to camphor).52 /3-Unsubstituted cyclohex-enones undergo exclusive and almost quantitative 1,4-reduction by potassium tri-s-butylborohydride to the corresponding saturated ketone [e.g. (16)] 53 reductive alkylation of carvone proceeds similarly to (17 R = Me, X = H).53 In contrast,... 

N. Chida, M. Ohtsuka, K. Ogura, and S. Ogawa, Synthesis of optically active substituted cyclohex-enones from carbohydrates by catalytic Ferrier rearrangement, Bull. Chem. Soc. Jpn., 64 (1991) 2118-2121. 

The best chiral resolution (68% ee) was obtained by the nonfunctionalised saturated NHC ligand, closely followed by the hydroxyethyl functionalised NHC (61% ee). However, the two catalysts afforded different enantiomers, the former the S ) enantiomer the latter the R +) enantiomer. This result seems to be representative. When alkyl substituted cyclohex-enones were used as substrates the products had the same R S distribution. 

Scheme 8). Conjugate addition of the resulting enamine-silyl ether to methyl a-trimethylsilylvinyl ketone in the presence of MgCl2 provided the cyclohex-enones. Using the prolinol-derived enamine, the annelated product was obtained with 77% ee.

N,P P, P] Danishefsky and Simoneau utilized the sequential Michael-aldol reaction for the synthesis of compactin and ML-236A (51.1 and 51.2 in Scheme 51) (101). In this context, the HgI2-promoted addition of the rerf-butyldimethylsilyl ketene acetal derived from ethyl acetate to cyclohex-enone 51.3 followed by reaction with crotonaldehyde and acidic work-up produces 35-42% of lactone 51.4 as one stereoisomer. As enone 51.3 is available in optically pure form from quinic acid (102), the naturally occurring enantiomer of compactin can be obtained. 

An interesting case contrasts the solid-state photochemistry of 2-methyl-4,4-diphenylcyclohexenone 9 with that observed in solution. Although only one product, 10, is formed in solution, in the crystal lattice, a second photoproduct, 11, is formed to an equal extent. The theoretical treatment of this is considered along with some further substituted cyclohex-enone photochemistry, which follows. 

It is clear from these examples that oxygenated dienes are convenient and useful precursors to cyclohex-enones and 7-oxabicycloheptane derivatives. Typical disconnections for oxygenated dienes are... 

Pyrrolidine-tetrazole 108 is also a very useful catalyst for the conjugate addition of a wide variety of nitroalkanes to cyclic and acyclic enones using /ranx-2,5-dime-thylpiperazine as base (Scheme 2.55) [161]. Excellent enantioselectivities (94-97% ee) are obtained for the addition of primary and secondary nitroalkanes to cyclohex-enone and 3-methyl-2-cyclohexenone. On the other hand, the level of enantioselection displayed by catalyst 108 in the case of the conjugate addition to acyclic enones is similar to that obtained with catalyst 107 (Scheme 2.55). 

The application of BINOL derivatives 256 in the MBH-reaction of cyclohex-enone 257 with aldehydes has been more interesting (Scheme 4.45). Triphenyl phosphine (100 mol%) was used as a nucleophilic promoter in THF at O C. Optimal yields and enantioselectivities were achieved using aliphahc aldehydes, while the use of benzaldehyde or p-nitrobenzaldehyde led to worse results [332]. 

Irradiation of 2,3-benzo-6,6-dimethylcydohepta-2,4-dienone gave a mixture of two dimers, (208) and its isomer with the opposite configurations at C-1 and C-9. These may have been formed by a photochemical [ 4s + 2a] cycloaddition, followed by a 1,3-acyl shift.Irradiation of cyclo-octa-2-en-l,4-dione gave the dimer (209), whereas irradiation in the presence of cyclopentadiene or furan gave the [4 + 2] adducts (210 X = O or CH2), and irradiation in methanol gave the methanol adduct, 2-methoxycyclo-octa-l,4-dione. The photochemical cycloadditions of cyclohex-enone to cycloheptatriene, cycIo-octa-l,3-diene, and cyclo-octa-1,5-diene, and of cyclopentenone to cyclo-octa-1,3-diene, have been studied. ... 

The UV and IR spectra of alkaloids with a cyclohexadienone or cyclohex-enone ring, including proaporphines, homoproaporphines, and morphinandi-enones have been discussed and compared. Some of the available UV data are given below. ... 

Identification of the four-carbon methyl vinyl ketone unit within the cyclohex-enone TM leads to the appropriate disconnections. The first retrosynthetic step is a retro-aldol, so a disconnection is made between the alpha and beta carbons. The alpha carbon will be introduced as an enolate nucleophile the other carbon was a carbonyl electrophile. 

These annulations are governed by conformational factors. In 1968 Johnson predicted that the dominant conformation for C(3),C(4)-dialkyl-substituted cyclohex-enones, such as 5, has the C(4) substituent oriented axially because of A-strain (Eq. 7)P In addition, the diene moiety of S can exist in either a transoid or a cisoid conformation, cf. conformations lii and iv, respectively. In simple acyclic 1,3-dienes, the planar transoid conformation is more stable than the cisoid form. However, examination of a Drieding model of iii suggests that nonbonded steric interactions tween the equatorial C(4) methyl substituent and the C(3) vinyl group would force the dienone into a cisoid conformation. This orientation clearly precludes 1,6-nucleophilic attack by the silicate species thus, 1,4-addition occurs to generate a cyclopentane ring. 

The diastereoselective [2 + 2] photocycloaddition between cyclohex-enones supporting a chiral 8-(p-metho yphenyl)menthyl auxiliaiy and olefins has been conducted in aqueous media using sodium dodecyl sulfate or dodecylamine hydrochloride as surfactants. ... 

Obtained by reaction of aniline with 2-acetyl-3-di-methyl-amino-5-hydroxy-5-methyl-2-cyclohex-enone in refluxing ethanol (17%) [2712]. 

The ability of chiral binaphthol (BINOL) derivatives as a Br0nsted acid catalyst to facilitate asymmetric transformations was demonstrated by Schaus by the development of the highly enantioselective Morita-Baylis-Hilhnan reaction of cyclohex-enone with aldehydes effectively catalyzed by (R)-octahydro-l,l -bi-2-naphthol derivatives, bearing either 3,5-bis(trifluoromethyl)phenyl (24a) or 3,5-xylyl (24b) groups at the 3,3 -positions, in combined use with triethylphosphine as a nucleophilic promoter (Scheme 7.43) [68]. 

In 2006, Gong and coworkers reported the first chiral Br0nsted acidotalyzed asymmetric direct aza-hetero-Diels-Alder reaction [70]. Phosphoric acid catalyst 160 exhibited excellent catalytic activity and selectivity for the reaction of cyclohex-enone (31) with a broad range of aldimines 159 to produce N-containing heterocycles 162 with up to 87% ee (Scheme 38.47). More recently, Carter and coworker developed the modified proHne catalyst 161 for this reaction, and high levels of enantioselectivity and diastereoselectivity were obtained (Scheme 38.47) [71]. Interestingly, the aromatic imines favor exo products while the ahphatic imines favor endo products. 

Chiral phosphoric acids also catalyze [4+2] cycloadditions. Gong and colleagues showed that 99c activates aromatic aldehydes 207, anisidine (119), and cyclohex-enone (206) to give the hetero-Diels-Alder products 208 and 209 with good yield and enantioselectivity, along with moderate endo-selectivity (Scheme 42.48) [104]. 

The Fe(CO)5-mediated [5-1-1] carbonylation of vinylcyclopropanes and CO had also been used in the synthesis of natural products by Taber et al. (Scheme 17.9) [13]. For example, this method was used to synthesize the cyclohex-enone core of sesquiterpene (—)-delobabone [13a]. In the... 

The tendency for exo addition to norbomene is also seen in Magomedov and co-workers results (Scheme 19.6). Exposure of cross-conjugated dienone 16 (Ts=/i-toluene-sulfonyl) to the sterically demanding Lewis acid MAD and triethylamine at room temperature furnished cyclohex-enone 17 in 91% yield as a single isomer. 

In 2011, Vaccaro et al. and Kobayashi et al. independently reported on chiral Sc(OTf)3/bipyridine-catalyzed sulfa-Michael additions to enones 264 in water. High yields and enantioselectivities were obtained for aliphatic thiols and acyclic enones, but the use of benzenethiol or cyclohex-enone failed to deliver optimal selectivity. 

Zimmerman, H.E. and Earners, P.H., Photochemistry of some extended 7t-systems type A and aryl rearrangements of systems with extended conjugation related to cyclohexadienones and cyclohex-enones. Mechanistic and exploratory organic photochemistry, /. Org. Chem., 54, 5788,1989. 

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