Conformational restriction methyl groups

B.2.9-12.) The interaction between an o-methyl group and an a cr-di-methyl-substituted chain is particularly severe, and undoubtedly leads to restricted rotation about the ring-chain bond (see Lomas and Dubois, 1978). This is not itself a major source of high effective molarities, however, as shown by the moderate EM s for compounds like [20] and [21] which have naturally restricted conformations (Danforth et ai, 1976). 

The preceding prediction rules are largely restricted to acyclic compounds. But there is also a considerable need for parameter sets enabling the spectroscopist to calculate I3C chemical shifts of conformationally defined cyclic molecules, especially of the cyclohexane type. Methyl-group effects in methylcyclohexanes (100,101) that are to be added to the basic value for cyclohexane itself (8 = 27.3) are listed in Table 29. Analogous methyl-group parameters in tetralins and tetra-hydroanthracenes have been reported (403). 

The predicted low enantiocontrol from reactions performed with methallyl diazoacetate (Eq. 5.18) was borne out in reactions catalyzed by Rh2(MEPY)4 and Rh2(MEOX)4, but when chiral imidazolidinone-ligated dirhodium(II) was used, enantioselectivity rose to 89% ee (Table 5.8) [89]. The use of CuPF6/7b also caused relatively high enantiocontrol (87% ee) [92] which, however, decreases to 82% ee when the methyl group of 36 was replaced by n-butyl, whereas with Rh2(4S-MPPIM)4 the enantiopurity of the product corresponding to 37 was 93% ee. The A-3-phenylpropanoyl substituents of Rh2(4S-MPPIM)4 help to create a more conformationally restrictive environment that leads to enhanced enantiocontrol. 

Figure 4.2 Harmes et al. suggest that the lack of antihistamine activity in the ortho-methyl analogue of diphenyhydramine is due to the ortho-methyl group restricting rotation about the C-O bond. It is believed that this prevents the molecule from adopting the conformation necessary for antihistamine activity...

A five-line e.s.r. spectrum is recorded. Evidently, the grafted polymer on the photoirradiated cellulose had a conformation that restricted rotation about the Ca - Cg bond, so that only one of the methylene hydrogens and the freely rotating methyl group interact with the unpaired electron (17). 

The authors suggested244 that proton loss [Eq. (185)] is controlled by stereo-electronic considerations and not by the thermodynamic stability of the product. In the preferred conformation, the tertiary hydrogen on the isopropyl group of the p-cymene radical cation is located in the nodal plane of the benzene ring where its interaction with the n system in the transition state is minimized. The methyl group, on the other hand, rotates rather freely, and the loss of any one of the hydrogens is, therefore, not conformationally restricted. 

This evidence, as well as that presented by other authors, has led Liquori et al. to conclude (d) that in the tightly coiled random chains of PMA most of the methyl groups have to be conceived of as being in the interior of the coils together with a fraction of the carboxyl groups, compatible with the obvious steric restrictions controlling the local conformation of the chain. 

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