2- Decalone methylation

Structurally rigid substrate surrogates were added to the cubic section model before more flexible molecules as the following order signifies pentacyclic, tetracyclic, tricyclic, bicyclic ketones, trans/cis-decalones, methyl cyclohexanones and alkyl cyclohexanones. The hydroxyls of cyclohexanols were oriented axially with respect to cyclohexyl rings consistent with the Jones protocol and with the obsen/ation that... 

The bromination given in the preceding experiment may be applied to trans-lO-methyl-2-decalone prepared in Chapter 3, Section III. The product is recrystallized from petroleum ether-benzene (10 1) giving colorless needles, mp 101-103°. 

A 7.5 g sample of c/5-10-methyl-2-decalon-9-ol is mixed with 100 ml of 10% aqueous potassium hydroxide and steam distilled, about 1 liter of distillate being collected. The distillate is saturated with sodium chloride and extracted three times with 100-ml... 

Using 3-substituted cyclohexanones the /rans-diastereoselective synthesis of decalones and octahydro-1 //-indenones may be achieved 164 169. This method has been applied, for instance, in the synthesis of 19-norsteroids. In a related Michael addition the lithium enolate of (R)-5-trimethylsilyl-2-cyclohexenone reacts with methyl 2-propenoate selectively tram to the trimethylsilyl substituent. Subsequent intramolecular ring closure provides a single enantiomer of the bicyclo[2.2.2]octane170 (see also Section 1.5.2.4.4.). 

The enzyme derived from Pseudomonas sp. strain HI-70 is able to oxidize a wide range of substrates including C12-C15 ketones, C5 and Cg ketones with methyl substituents, and some bicyclic ketones including decalones (Iwaki et al. 2006). 

The stereoselectivity is enhanced if there is an alkyl substituent at C(l). The factors operating in this case are similar to those described for 4-r-butylcyclohexanone. The tnms-decalone framework is conformationally rigid. Axial attack from the lower face leads directly to the chair conformation of the product. The 1-alkyl group enhances this stereoselectivity because a steric interaction with the solvated enolate oxygen distorts the enolate to favor the axial attack.57 The placement of an axial methyl group at C(10) in a 2(l)-decalone enolate introduces a 1,3-diaxial interaction with the approaching electrophile. The preferred alkylation product results from approach on the opposite side of the enolate. 

A similar dissection of the excited states responsible for reaction by quenching has been carried out on cis- and /ra 5-8-methyl-1 -hydrindanone and cis- and frans-9-methyl-l-decalone with the purpose of determining the... 

Dimethylcyclohexanone and 2-benzyl-2-methylcyclohex-anone have been prepared similarly in yields of 60% and 55%, respectively.2 The procedure has been extended to the synthesis of 9-methyl-, 9-w-butyl-, and 9-benzyl-l-decalone from the dianion of 2-formyl-l-decalone in yields of 55%, 48%, and 58%, respectively.2... 

Intramolecular cyclizationlenolate trapping of allylsilanes (cf., 12,496-497).3 The intermediate enolate formed in the TiCl4-catalyzed cyclization of 1 can be trapped by chloromethyl methyl sulfide to give a decalone derivative with a potential methyl group on the angular position. Actually the reaction results in... 

In fact, a similar intramolecular cyclisation was studied by Reusch [11] and he found a remarkable methyl substituent effect on the aldol equilibrium. Starting from the cis-decalones 25 (easily prepared from the Wieland-Miescher ketone), in which the angular methyl group prevents isomerisation to the more stable trans-decalone, it was found that other methyl groups may exert profound but less... 

However, as already stated [12] this is probably unnecessary, since in the basic medium in which the cyclisation takes place the rrans-decalone with no angular methyl group would be in equilibrium with the corresponding cii-decalone. Even in the less favoured case, the equilibrium would shift to the cis-isomer since this is the only isomer which can cyclise to twistanone. Should this be the case, then the stereochemical control in preparing the starting decalone would be unnecessary and the synthesis would be greatly simplified. 

Angular alkylations of fused-ring ketones are an important step in syntheses of terpenoids, steroids and related natural products. The steric course of these alkylations has therefore been the subject of several systematic investigations and has been reviewedl 3 71. Alkylation of the lithium enolate 38 (R = H) derived from octahydro-1 (2//)-naphthalenone (1 -decalone) primarily yields the civ-fused octahydro-8a-methyl-l(2F/)-naphthalenone (39, R = H)35,62,79. Due to steric reasons, the lithium enolate 38 (R = CH3), with an angular methyl group, provides the irans-fused product 39 (R = CH3). 

The copper-catalyzed conjugate addition of methyl magnesium iodide to cyclohexenone and trapping the enolate as its trimethylsilyl enol ether, followed by a trityl hexachloro-antinomate-catalyzed Mukaiyama reaction, is apphed to / -(—jcarvone. C-2, C-3 functionalized chiral cyclohexanones are converted into their a-cyano ketones, which are submitted to Robinson annulation with methyl vinyl ketone. Highly functionalized chiral decalones are obtained that can be used as starting compounds in the total synthesis of enantiomerically pure clerodanes (equation 70). 

Like other phenomena involving interactions between electromagnetic radiation and organic molecules, as in infrared, ultraviolet, and nmr spectroscopy, optical rotatory dispersion curves often are quite sensitive to small changes in structure. As an example, the rotatory dispersion curves for enantiomers of cis- and trcMr-lO-methyl-2-decalones, 16 and 17, are reproduced in Figure 19-7 ... 

Figure 19-7 Rotatory dispersion curves for c/s-10-methyi-2-decalone, 16, and trans-10-methyl-2-decalone, 17. (By permission from C. Djerassi, Optical Rotatory Dispersion, McGraw-Hill Book Co., New York, 1960.)...

In cis -fused decalones, two different conformations are possible, as in the steroid (f) and nonsteroid (g) conformers of Table 4. The octant rule predicts a strong negative Cotton effect for (f) and a strong positive Cotton effect for (g). Assuming chair conformations, nearly all of the ring atoms of (f) lie in octant symmetry planes (carbons 1, 2, 4, 7, 10 and the angular methyl) or have counterparts across the octant planes (carbons 3 and 5,... 

The contribution of the methyl substituent in 8-methyl-1-decalones 27 and 28 is octant consignate but different in magnitude for the axial and equatorial methyl group, though they are nearly symmetrically located with respect to the horizontal carbonyl plane". 

X-ray crystallographic analysis revealed that methyl cA-tetrahydro-a- (36) and -ft-santoninate (37) have a nonsteroid decalone conformation in the solid state. Furthermore, positive Cotton effects shown by both cis -fused decalone analogues indicated the presence of such nonsteroid conformation (38) in solution, in accord with the octant rule121. 

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