2-Methylcyclohexanone, chirality

Our research group developed catalytic enantioselective protonations of preformed enolates of simple ketones with (S,S)-imide 23 or chiral imides 25 and 26 based on a similar concept [29]. For catalytic protonation of a lithium eno-late of 2-methylcyclohexanone, chiral imide 26, which possesses a chiral amide moiety, was superior to (S.S)-imide 23 as a chiral acid and the enolate was pro-tonated with up to 82% ee. 

Since most often the selective formation of just one stereoisomer is desired, it is of great importance to develop highly selective methods. For example the second step, the aldol reaction, can be carried out in the presence of a chiral auxiliary—e.g. a chiral base—to yield a product with high enantiomeric excess. This has been demonstrated for example for the reaction of 2-methylcyclopenta-1,3-dione with methyl vinyl ketone in the presence of a chiral amine or a-amino acid. By using either enantiomer of the amino acid proline—i.e. (S)-(-)-proline or (/ )-(+)-proline—as chiral auxiliary, either enantiomer of the annulation product 7a-methyl-5,6,7,7a-tetrahydroindan-l,5-dione could be obtained with high enantiomeric excess. a-Substituted ketones, e.g. 2-methylcyclohexanone 9, usually add with the higher substituted a-carbon to the Michael acceptor ... 

The situation is different for 2-methylcyclohexanone. 2-Methylcvclo-bexanone has no symmetry plane and is chiral because C2 is bonded to four different groups a -CH3 group, an —H atom, a -COCH2- ring bond (C1), and a —CH2CH2— ring bond (C3). 

Finally, with the aim of discovering novel chiral oxomolybdenum catalysts able to perform enantioselective alkene epoxidations, Kuhn et al. have reported the exploration of the catalytic behaviour of a series of dioxomolybdenum(VI) complexes with chiral cw-8-phenylthiomenthol ligands derived from ( + )-pulegone. Therefore, the epoxidation of c -p-methylstyrene using t-butyl-hydroperoxide as the oxidant and performed in the presence of ( + )-(2i ,5i )-2-[1-methyl-l-(phenylthio)ethyl]-5-methylcyclohexanone oxime as the ligand, did not produce, however, a significant optical induction in these conditions. 

A) (23), was obtained in an improved yield using the modified literature procedure (28) starting from benzene diazonium chloride (1054) and hydroxymethylene-5-methylcyclohexanone (1055). A biomimetic coupling of l-hydroxy-3-methylcarba-zole (O-demethylmurrayafoline A) (23) by reaction with di-ferf-butyl peroxide l(t-BuO)2] afforded the dimer of O-demethylmurrayafoline A (204). Finally, oxidation of 204 with PCC afforded (+ )-bismurrayaquinone-A (215). The resolution of atropo-enantiomers was achieved by chiral HPLC using Chiracel OF. The assignment of the absolute configuration of the two enantiomers (S)-215 and (f )-215 was achieved by comparison of their theoretical and experimental circular dichroism (CD) spectra (166,167,661) (Scheme 5.164). 

The preparation of 2-isopropyl-6-methylcyclohexanone is strongly dependent on the sequential order of introducing the methyl and the isopropyl group. Metalation of the chiral 2-isopropyl-cyclohexanone imine and alkylation with iodomethane furnished only 18% yield, whereas a 95 % yield was obtained by first introducing the methyl group and alkylating in the last step with 2-iodopropane8. 

In 1968, Horeau et al.1441 reported an enantioselective methylation of cyclohexanone via an optically active terpenylimine to yield 2-methylcyclohexanone with 72% enantiomeric excess. The following deals only with those chiral amino compounds that are derived directly from amino acids 14S). 

Chiral 2,2-disubstituted cycloalkanones.1 The imine 2 prepared from racemic 2-methylcyclohexanone and (S)-( - )-l, reacts with methyl vinyl ketone to form an adduct that is hydrolyzed to the (R)-( + )-diketone 3 in 91% ee with recovery of 1 in almost quantitative yield. The reaction is described as a deracemizing alkylation. ... 

Diastereotopic faces also exist, as seen in the achiral 4-methylcyclohexanone (LXIV) and in the chiral 2-methylcyclohexanone (LXV). In contrast, cyclohexanone itself has two equivalent faces. 

S)-3-Methylcyclohexanone isn t racemized by base because its chirality center is not involved in the enolization reaction. 

Chiral -substituted ketones.2 Conjugate addition of (CH3)3A1 to the ketal (2) of cyclohexenone derived from (S,S)-1 followed by acetylation results in the adduct 3, which is hydrolyzed by acid to (S)-3-methylcyclohexanone (4) in 77% ee. The ketal derived from (2R,3R)-2,3-butanediol undergoes a similar conjugate addition with low asymmetric... 

The reaction of chiral phosphonium ylide or related reagent with a 4-substituted cyclohexanone gives an axially dissymmetrical alkene. For example, alkenation of 4-methylcyclohexanone (4.40) with chiral ylide 4.41 containing stereogenic centre on phosphorus gives optically active alkene (S)-(+)-4.42 in 43% yield . 

At an early stage Kitagawa and co-workers followed a path which, unfortunately, did not reach the goal (57). Starting from d-camphor, building block 43 (Scheme 10) was reached via various steps (58). Resolution of diastereomeric ketals of cyclopropanated 3-methylcyclohexanone likewise yielded the chiral... 

Stereoselective selenenylation of ketones with chiral selenamines has been utilized as a facile entry to optically active 4-substituted 2-cyclohexenones 9, but with low optical purity6. Thus, the reaction of 4-te/T-butyl- or 4-methylcyclohexanone with chiral selenamines in benzene or tetrahy-drofuran at various temperatures and/or times affords diastereomeric 2-arylseleno-4-/< /7-butyl-and 2-arylseleno-4-methylcyclohexanone (8). Oxidation of these selenides with hydrogen peroxide produces (S)-4-/erf-butyl- or (.S )-4-methyl-2-cyclohexenone (9) in quantitative yield6. 

Medium-sized cyclic ketones have been enantioselec-tively alkylated via their chiral lithioenamines to yield 2-alkylcycloalkanones in 80-100% ee. This procedure has also furnished a,a -dialkyl cyclohexanones in good enantiomeric excess (eq 2). Based on this protocol, regiospecific deutera-tion of 3-methylcyclohexanones has been achieved with good enantioselectivity. ... 

Chiral lactones can be formed from ketones via the Bacyer-Villiger reaction. Such lactones are potentially useful synthons for a number of natural products (37). Many of the examples of enantioselective lactone formation have been demonstrated using cyclohexanone oxygenase isolated from various Acinetobacter spedes (37,38). Figure 14 shows the enzymatic lactonization of methylcyclohexanone, which gave an 80% yield with an enantiomeric excess greater than 98%. 

R-3-Methylcyclohexanone desorption reveals the same types of easily assigned desorption features on many of the other chiral and achiral surfaces in the stereographic triangle [23]. 

Horvath JD, Baker L, GeUman A1 (2008) Enantiospecific orientation of R-3-methylcyclohexanone on the chiral Cu(643)" surfaces. 1 Phys Chem C 112 7637... 

With the aid of molecular models and diagrams, indicate whether you would expect the following to be chiral (a) trans-cyclohexane-1,2-dicarboxy Lie acid (b) 3-methylcyclohexanone (c) 1,1,4-trichlorocyclobexane (d) 1,1,2-trichlorocyclohexane (e)... 

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