C3 methyl group

Cholesterol is derived from the steroid skeleton by adding a hydroxyl group at C3, methyl groups at CIO and C13, an eight-carbon alkyl group at C17, and introducing a double bond between carbon atoms 5 and 6.1 have taken some pains to indicate the stereochemistry at each of the eight chiral centers in this molecule its shape matters. 

S-Diketones.1 /3-Diketones react readily with hydroxylamine to form isoxazoles and can be reformed by acid hydrolysis and thus can function as / -diketone synthons. For example, 3,5-dimethylisoxazole, readily obtained from acetylacetone, can be metallated by a variety of bases, and the anion so obtained can be alkylated at the C5-methyl group. A second alkylation occurs only at the C3-methyl group. Thus it is possible to prepare selectively 3,5-dialkylisoxazoles, from which the corresponding / -diketones are obtained in 70-95% yield by acid hydrolysis in ethanol. 

Examples of selective side-chain oxidation were reported for two reagents Ceric ammonium nitrate was found to convert 5-methylpyrrole-2-carboxylates to 5-formylpyrrole-2-carboxylates. <95TL4345> Several examples of oxidation of C2 and C3 methyl groups to formyl in 1-(phenylsulfonyl)indoles with Mn02 were reported. <95SC2407>... 

Michael-aldol ring-closures In another variant, the addition of an amine base to the 3,4-dimethyl anisolium species 52 results in deprotonation at the benzylic C3 methyl group,... 

Clearly, the zwitterionic peroxide (213) is implicated (Scheme 27). Closure to the dioxetane (214) and scission to (210) is a minor event. Capture of (213) by aldehyde predominates. The epimeric cM-fused trioxanes (211) arise from the syn or anti arrangement (215). The major epimer, identified by x-ray, has the C3 methyl group disposed cis with respect to the indole ring. The trans epimer is unstable and cannot be isolated. The structure of the minor position isomer (212) follows from its NMR spectrum. It probably derives from the addition of the alternative benzylic zwitterionic peroxide (216) to acetaldehyde. 

The diastereoselectivity of the IMDA is rationalized in Figure 19.5. Within the ordered transition state of the thermal cyclization, conformation A is disfavored due to allylic A strain. The fevored conformation B facilitates the facial selectivity of C3a-C9a bond formation engendering a c/s-relations ship between the C3 methyl group and 3 hydrogen in 16. The relative stereochemistry between C3a and C9a is a function of the exo-selective nature of the IMDA, and the relative stereochemistry between Csa and C4 is controlled by the choice of cw-dienophile. The C9a stereogenic center was readily epimerized by treatment with DBU. Catalytic reduction of the internal double bond incorporated the stereogenic center at Cga in the required relative stereochemistry (see Scheme 19.1). In short, the... 

The lactone ring is essential for PAR-1 activity. The lactone ring does not remain opened as the carboxylic acid-alcohol because it spontaneously cyclizes, presumably due to the Thorpe-Ingold effect exerted by the methyl group. Reduced versions of the lactone, such the fused tetrahydrofuran and diol (not shown) are far less active. The C3 methyl group is optimal, whereas the C3... 

For a symmetric rotor molecule such as methyl fluoride, a prolate symmetric rotor belonging to the C3 point group, in the zero-point level the vibrational selection mle in Equation (6.56) and the character table (Table A. 12 in Appendix A) show that only... 

Figure 3.9 A plot of potential energy versus rotation for the C2-C3 bond in butane. The energy maximum occurs when the two methyl groups eclipse each other, and the energy minimum occurs when the two methyl groups are 180° apart (anti. ...

The energy difference between axial and equatorial conformations is due to steric strain caused by 1,3-diaxial interactions. The axial methyl group on Cl is too close to the axial hydrogens three carbons away on C3 and C5, resulting in 7.6 kj/mol of steric strain (Figure 4.13). 

Here N represents the order of the rotation axis, i.e, N = 3 for the hindered rotation of a methyl group about its C3 symmetry axis (see Chapter 9). 

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