Polar addition activated double

However, better results have been reported when the polarity of the reaction is reversed. In this indirect path, an initial radical addition of a thio- or selenophenyl group affords a compound that can be the precursor of a difluoromethyl radical. This latter species can further add onto an activated double bond. These radical approaches have also allowed the synthesis of glycopeptides and difluorophosphonates (Figure... 

The Adg3 occurs when the cation is not as stable. Instead of proton transfer, a pi-complex forms, which polarizes and activates the double bond. The nucleophile attacks the largest partial plus of the complex and gives the same Markovnikov orientation of product as the Adg2 process. The pi-complex usually blocks one face of the double bond, therefore the nucleophile adds to the opposite face, giving overall anti addition as the predominant process. Adg3 Example ... 

Examples of activated double bond electrophiles include a, 3-unsaturated carbonyl compounds, quinones, quinoneimines, quinonemethides and diiminoquinones as shown in Fig. 10.32B. These electrophilic intermediates are highly polarized and can react with nucleophiles in a 1,4-Michael-type addition at the more electrophilic or 3-oarbon of the activated double bond intermediate to the addition product (Fig. 10.32A). Specific examples of activated double bond electrophiles that have been proposed for the anticancer drug leflunamide, the food antioxidant butylated hydroxytoluene, acetaminophen, the antiandrogen flutamide, the anticonvulsant felbamate and the cytotoxic cyclophosphamide as shown in Fig. 10.32C. The bioinaotivation pathways for these electrophilic intermediate can involve either direct addition, with or without transferases, depending upon the degree of polarization and reactivity of the electrophilic intermediate (hard vs soft electrophiles). 

Monoalkyl H-phosphonates exhibit a different reactivity toward addition to double bonds depending on the type of the cation. The metal salts, which add more easily, have been shown to exist as contact-ion pairs [287]. In this case, coordination of the corresponding metal cation to the phosphoryl oxygen is suggested to activate the P-H bond. Similar complex formation is not possible for ammonium salts, which exist as free ions in polar solvents. 

A number of groups have criticized the ideas of Dauben and Noyce, especially the concept of PDC. Kamernitzsky and Akhrem, " in a thorough survey of the stereochemistry of addition reactions to carbonyl groups, accepted the existence of SAC but not of PDC. They point out that the reactions involve low energies of activation (10-13 kcal/mole) and suggest that differences in stereochemistry involve differences in entropies of activation. The effect favoring the equatorial alcohols is attributed to an electrostatic or polar factor (see also ref. 189) which may be determined by a difference in the electrostatic fields on the upper and lower sides of the carbonyl double bond, connected, for example, with the uncompensated dipole moments of the C—H bonds. The way this polar effect is supposed to influence the attack of the hydride is not made clear. 

The Woodward-Hoffmann rules predict high activation energies for the suprafacial-suprafacial addition of two carbon-carbon double bonds, these may be lowered by polar effects (74AF(3)75i). [2 + 2]... 

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