Gem-Dialkylation

Butaprost (82) not only has the typical C-15 hydroxyl of the natural prostaglandins moved to C-16, as do several of the analogues discussed above, but it has a rather interesting gem dialkyl substitution at C-17, presumably for metabolic protection, in the form of a cyclobutyl ring. It is a bronchodilator and is prepared in a manner analogous to that of rioprostil discussed above [17]. 

The gem-dialkyl effect as a function of ring size relative EM s for the formation of small rings... 

For amine cyclizations it is possible to introduce gem-dialkyl substitution at the nucleophilic centre, and the data in Table 9 suggest that a similar but reduced effect may operate in this position also. The accuracy of the EM s given in Table D.3 is not such that absolute magnitudes are very significant, but the relative magnitudes in this series are reliable since the rate constants on... 

When terf-butyl p-nitrobenzoate was used, the desired allylic esters were obtained in high enantiomeric excesses, albeit in low yields, in the presence of copper/bisoxazoline (Scheme 5.24). The reason for high enantioselectivities was attributed to the use of terf-butyl p-nitrobenzoate and gem-dialkyl bisoxazo-... 

The photochromic compounds of potential interest, based on the 2//-chromene ring system, are the 2//-benzopyrans (1.18) or the three isomeric naphthopyrans (1.19-1.21). However, 2H-naphtho[2,3-( ]pyrans (1.21) show little or no useful photochromic behaviour and can be discounted from any further discussion. Although R and can be part of a carbocyclic spiro ring, they are more commonly unconnected substituents such as gem dialkyl or aryl groups. 

The metal plays a crucial role in these reactions. (CH3)3AI and TiCI (1 l)also induce gem-dialkylation of ketones, but(CH3)3Al and A1C13 are ineffective. 

D. B. Tulshian, R. Tsang, and B. Fraser-Reid, Out-of ring Claisen rearrangements are highly stereoselective in pyranoses Routes to gem-dialkylated sugars, J. Org. Chem. 49 2347 (1984). 

The main problem a peptide chemist has to tackle with CMetrasubstituted a-amino acids is their rather poor reactivity in peptide-bond formation due to steric hindrance at the a-carbon. In addition, during the activation process of the carboxylic function of peptides and urethane or amide N-protected derivatives, an intramolecular reaction leading to the oxazoI -5 (4 //) -on e heterocyclic skeleton is greatly favored by the gem-dialkyl effect (Scheme... 

The oxazol-5(4//)-one coupling method (Scheme 4) is uniquely appropriate for C -tetra-substituted a-amino acids, since racemization or epimerization is unlikely to occur with these compounds. It represents the main methodology exploitable for fragment condensation of peptides based on C -tetrasubstituted a-amino acids. Due to the gem-dialkyl effect on the C°... 

Recently, much effort has been directed to the synthesis of analogs of the biologically active form of vitamin D3, la,25-dihydroxyvitamin D3 [la,25(OH)2D3] as an important new field in medicinal chemistry [50], As a new and efficient route to this class of compounds, the symmetry -assisted enantiospecific synthesis of the A-ring of the vitamin D-hybrid analogs, 19-nor-22-oxa-la,25(OH)2D3 was reported (Scheme 8C.20) [51]. It should be noted that any gem-dialkyl substituents is not necessary to attain a high level of enantioselectivity. 

A facilitated transition hypothesis has been suggested to replace the reactive rotamer hypothesis as an explanation for the gem-dialkyl effect in intramolecular cyclization reactions.59... 

Since /-alkyl chlorides can be obtained from ketones, this cyanation represents a method for gem-dialkylation of ketones. 

Jung, M. E. Gervay, J. gem-Dialkyl effect in the intramolecular Diels-Alder reaction of 2-fur-furyl methyl fumarates the reactive rotamer effect, enthalpic basis for acceleration, and evi-... 

Asymmetric intramolecular Diels-Alder reaction.1 This chiral Ti catalyst system 4 is also effective for enantioselective intramolecular Diels-Alder reactions (equation I). In this particular case, a dithiane group accelerates the rate and enhances the em/o-selectivity, and is comparable to the gem-dialkyl effect. 

In Section 3.5.1, it was mentioned that Br2 and Cl2 form resonance-stabilized benzyl cation intermediates with styrene derivatives and that gem-dialkylated alkenes react with Br2 hut not... 

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