Gem-dimethyl substituents

Catalyst Study. Equivalent amounts of p-phenylenebis(4,4-dimethyl-2-oxazol1n-5-one ) (2) and Jeffamine D-2000 (polyoxypropylenediamine from Texaco Chemical Co., amine equiv. weight 1023) were mixed with 5 mole % of the desired catalyst. The stirred mixture was heated at 240°C under argon for 30 minutes, then an additional 1.5 hours under vacuum (<1 torr) and collected. The amount of cyclization was estimated by 1H-NMR in CDC 13 by comparison of the Integrated intensities of the absorptions due to the gem-dimethyl substituents. These absorptions appeared at 1.39 ppm in the cyclic form and at 1.73 ppm in the open-chain form of the polymer (see Scheme 4). Results are listed in Table I. 

Ni11 complexes with tri-, tetra-, penta-, and hexa-thia crowns have been studied.1675-1683 It has been shown that peripheral macrocycle modifications may lead to substantial improvements in Ni11 complexation gem-dimethyl substituents at the [14]ansS4 macrocycle (e.g., (659), (660))... 

The very good yields of especially the bridgehead alkoxy derivatives 231 and the excellent regioselectivity with which they can be transformed to other skeletons plus the fact that a spirocyclopropane moiety is a mimic of and can in fact be considered as a masked gem-dimethyl substituent [28, 112] makes these products versatile precursors of certain natural products. In fact, one may conceive new approaches to the total syntheses of taxol [113-115] and of mediter-raneol [116]. Both strategies rely on the MIMIRC reaction of lithium cycloalka-dienolates [117] with the a-chloro acrylate 1-Me to produce a tricyclic precursor to the appropriate bicyclo [n.2.1]alkanedione derivative, which are key structural units of several diterpenes and their metabolites. 

Friedel-Crafts acylation of 4-bromoindole led to 67, which, after protection by N-tosylation to give 68, was treated with methylmagnesium bromide and afforded compound 66, which contains the welwistatin C3-C16 bond as well as its gem-dimethyl substituent at C(16). A Lewis-acid catalyzed displacement of the tertiary hydroxyl in 66 by a cyclohexanone silyl enol ether afforded intermediate 69, which was then deprotected and N-mclhylalcd to 70 (Scheme 13). 

As indicated from computational studies, the catalyst-activated iminium ion MM3-2 was expected to form with only the (E)-conformation to avoid nonbonding interactions between the substrate double bond and the gem-dimethyl substituents on the catalyst framework. In addition, the benzyl group of the imidazolidinone moiety should effectively shield the iminium-ion Si-face, leaving the Re-face exposed for enantioselective bond formation. The efficiency of chiral amine 1 in iminium catalysis was demonstrated by its successful application in several transformations such as enantioselective Diels-Alder reactions [6], nitrone additions [12], and Friedel-Crafts alkylations of pyrrole nucleophiles [13]. However, diminished reactivity was observed when indole and furan heteroaromatics where used for similar conjugate additions, causing the MacMillan group to embark upon studies to identify a more reactive and versatile amine catalyst. This led ultimately to the discovery of the second-generation imidazolidinone catalyst 3 (Fig. 3.1, bottom) [14],... 

The results (4) do not support the conclusion that the rates for the norbomyl derivatives exhibit major enhancements. For example, the rate of solvolysis of camphene hydrochloride (/) is faster than that of the tetraniethylcyclopentyl chloride (7) by a factor of only 5.7. Such a factor is far too small to argue for a major new stabilizing phenomenon in the ion from 1. Removal of the gem-dimethyl substituents decreases the rate from 13,600 for 1 to 355 for 8. A similar effect is observed in the cyclopentyl derivatives, 7 and 9. These changes in reactivity are far more compatible with relief of steric strain13 than with resonance stabilization of the cations 12 ... 

The expected rate-enhancing effects of gem-dimethyl substituents were not seen in the base-catalysed cyclizations of ethyl A-(4-nitrophenyl)hydantoate (106 R, = Me, R = 4-O2NC6H4) and of ethyl A-phenylhydantoate (106 R R = Me, R° = Ph). Solvent kinetic isotope effects and other data led to the conclusion that the loss of the gem-dimethyl effects was due to steric hindrance to proton transfer of... 

Comparison of the polymerization behavior of 1-methylazetidine with that of 1,3,3-trimethylazetidine shows the importance of the gem-dimethyl substituents in the 3-position. With the former monomer, a termination reaction occurring between the active species and an amino function of the polymer, leading to branched or macrocydic ammonium salts, was observed," whereas with the latter this termination is virtually nonexistent as a consequence of steric shielding of the amino functions in the polymer chain. 

In the absence of gem dimethyl substituent at C-3, a di-n-methane rearranged product still formed from 1, 4-diene, but through a 1, 2-shift in contrast to previous mechanism. However, this is confirmed by deuterium labeling. 

Epoxidation reactions are well known to respond to steric effects and are generally observed to occur diastereoselectively from the less hindered face of an olefin. Two selected examples that showcase this feature are illustrated below. The presence of the C7-gem-dimethyl substituents on the norbornene skeleton (7,7-dimethylnorbornene, 3, Equation 2) overrides the inherent proclivity for the unsubstituted norbornene (1, Equation 1) to undergo epoxidation from the exo face [51]. 

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