Alkyl geminal substitution

The mono-alkylated species N3P3C15R is a good synthon for the generation of geminally substituted products by further reaction with Grignard reagents (Eq. 4) (150)... 

Hyperconjugation does not seem to have much effect on alkene reactivity towards bromine, since (16) applies whatever the number of alkyl groups on the double bond. However, only cis-olefins are involved in this correlation. To include geminally substituted olefins, an additional term is necessary, as in (19) where d is unity for the pem-disubstituted compounds and zero for... 

With sodium methoxide, arylidene derivatives 209 undergo a rearrangement into photochromic dihetaryl-substituted cyclopentenediones 211. They are easily alkylated to form geminally substituted products 212 in 91-94% yields (07MC301). Their photochemical properties were investigated (07OS975, 08IZV853). 

A variety of geminally substituted cyclopropyl ethers are synthesized employing Fischer carbene complexes [(CO)5M=CR (OR2) M = Cr, Mo, W R1 = alkyl, alkenyl and aryl] as alkoxycarbene sources. Electron-deficient alkenes and conjugated dienes are suitable substrates for the reaction (equation 108)237-245. Electron-rich enol ethers and enamines are also... 

Geminal substituted dibromoalkenes can be prepared by the alkylation of dibromomethyllithium with a-chloroalkyl methyl ethers. Deprotonation of the alkylation products results in the elimination of methanol and the formation of the corresponding 1,1-dibromoalkenes. Despite the lower acidity of 1 -bromo-1 -chloroalkyllithiums relative to the dibromo analogs they exhibit similar nucleophilic proper-ties. Alkyl dichloroacetates can also be deprotonated with lithium diethylamide and alkylated with a range of alkyl halides. ... 

Alkylation of 2- and 4-cyanocholestan-3-one derivatives provides a method for controlling the site of substitution of such unsymmetrical ketones and gives geminally substituted products whose stereochemistry is not readily obtainable by other means. ... 

Fig. 4.30) with various substitution pattern at Cl and C2 were investigated. Experiments with alkyl substituents at C2, in place of the sulfur heteroatoms, eliminate the viability of a chelation-controlled selectivity and reveal the significance of geminal substitution [geminal substitution influenced the selectivity in other oxocarbenium ion systems [108]]. Perturbation of the Cl substituent of the oxocarbenium ion intermediate has little effect on reaction stereoselectivity, and analysis of this observation lends additional support for stereoelectronically preferred inside attack of the nucleophile. The results demonstrate that selective formation of the 1,4-c/s product 84 does not require a chelated transition stracture, reinforcing the utility of the inside attack model to analyze the reactivity of complex five-membered ring oxocarbenium ion intermediates. 

The reactivity of allyl radicals does, however, appear to be sufficient for intramolecular radical reactions. In a systematic study, Stork and Reynolds investigated the feasibility of allyl radical 5-exo cyclizations41. It was found that cyclization proceeds readily for a variety of systems, especially for those with geminal 3,3-diester substitution. Mixtures of c/s/fraws-cyclopentanes are formed as the major products, while 6-enclo cyclization is hardly observed42. Allyl radicals behave in this respect much like alkyl radicals43. Cyclization is not even hindered by the presence of substituents at the attacked carbon... 

Martin and Martin 51) have reported similar small (AJ= -0.2 to -0.45 Hz) changes for VHH in a series of alkyl substituted vinyl bromides. The same authors si> have repeated a 1.5 Hz decrease with increasing solvent polarity for the negative geminal coupling constant in allenic ketones of the form RCOCH = C=CH2 where R is methyl or ethyl. Reaction field interactions are suggested. 

Tables 5.2 and 5.3 give characteristic shifts for nuclei in some representative organic compounds. Table 5.4 gives characteristic chemical shifts for protons in common alkyl derivatives. Table 5.5 gives characteristic chemical shifts for the olefinic protons in common substituted alkenes. To a first approximation, the shifts induced by substituents attached an alkene are additive. So, for example, an olefinic proton which is trans to a -CN group and has a geminal alkyl group will have a chemical shift of approximately 6.25 ppm [5.25 + 0.55(tra .s-CN) + 0.45(gew-alkyl)].

Highly regioselective ene reactions of singlet oxygen with alkyl-substituted alkenes can also be used for synthetic purposes. For example, in the photooxygenation ofl-t-butylcycloheptene only one allylic hydroperoxide, by the exclusive geminal hydrogen... 

Strategies centered on reductive introduction of the fluoroolefin via a geminal difluoro allylic array have been reviewed [66]. In an introductory example to this synthetic approach, Okada et al. [67] developed a completely stereoselective synthesis of Z)-2,5-syn 2-alkyl-4-fluoro-5-hydroxy-3-alkenoic acids through the Cu(l)-mediated allylic substitution reaction of trialkylaluminum with the (E)-4,4-difluoro-5-hydroxyallylic alcohol derivative (61) (Scheme 21). Reaction... 

Ethylene dithioacetals of benzophenone and its 4-fluoro-, 4-bromo-, 4,4 -difluoro-, 4,4 -dichlo-ro-, and 3,5-dimethyl-substituted analogs react with sulfuryl chloride or sttlfuryl chloride fluoride in hydrogen fluoride/ pyridine at — 78 C to room temperature to give the corresponding geminal difluorides in 85-90% yield. The reaction is, however, not applicable to dialkyl or alkyl aryl ketones as they undergo chlorination under these conditions.73... 

Butadienes with alkyl substituents in the 2-position favor the formation of the so-called para-products (Figure 15.25, X = H) in their reactions with acceptor-substituted dienophiles. The so-called mefa-product is formed in smaller amounts. This regioselectivity increases if the dienophile carries two geminal acceptors (Figure 15.25, X = CN). 2-Phenyl-1,3-butadiene exhibits a higher para -selectivity in its reactions with every unsymmetrical dienophile than any 2-alkyl-1,3-butadiene does. This is even more true for 2-methoxy- 1,3-butadiene and 2-(trimethylsilyloxy)-l,3-butadiene. Equation 15.2, which describes the stabilization of the transition states of Diels-Alder reactions in terms of the frontier orbitals, also explains the para "/"meta "-orientation. The numerators of both fractions assume different values depending on the orientation, while the denominators are independent of the orientation. 

Butadienes with alkyl substituents in the 2-position favor the formation of the so-called para products (Figure 12.24, X = H) in their reactions with acceptor-substituted dienophiles. The so-called meta product is formed in smaller amounts. This orientation selectivity increases if the dienophile carries two geminal acceptors (Figure 12.24, X = CN). 2-Phenyl-l,3-butadiene exhibits a higher para selectivity... 

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