Regioselection in nucleophilic addition

Szabo, K. J. Effects of 3-Substituents and Ancillary Ligands on the Structure and Stability of (T -Allyl)palladium Complexes. Implications for the Regioselectivity in Nucleophilic Addition Reactions. J. Am. Chem. Soc. 1996, 118, 7818-7826. 

Directionality and Regioselection in Nucleophilic Addition to Dicarbonyl Compounds... 

The regioselectivity in radical addition reactions to alkenes in general has successfully been interpreted by a combination of steric and electronic effects1815,47. In the absence of steric effects, regiochemical preferences can readily be explained with FMO theory. The most relevant polyene orbital for the addition of nucleophilic radicals to polyenes will be the LUMO for the addition of electrophilic orbitals it will be the HOMO. Table 10 lists the HOMO and LUMO coefficients (without the phase sign) for the first three members of the polyene family together with those for ethylene as calculated from Hiickel theory and with the AMI semiempirical method48. 

The origin of the regioselectivity of nucleophilic addition to the Ti3-intermediate can be understood with reference to the interactions which take place in the intermediate itself In the situation with a... 

It seems that the repulsive steric interactions play a more dominant role in regioselectivity of aryne reactions than is sometimes realized. In fact, it has been argued that in nucleophilic addition to arynes, the transition state is reached early, while the incipient bond is still very much extended. Consequently, steric effects were considered not to be of great importance.80 81 It should, however, be noted that the dehydro bond orbitals are so oriented that the optimal approach trajectory for the nucleophile lies in the... 

Regioselectivity in the Addition of Soft Carbon Nucleophiles to ir-Allylpalladium Complexes 627... 

It is clear that although substantial progress has been made in the understanding and control of regioselectivity in the addition of nucleophiles to Tr-allylpalladium complexes via attack at the metal, considerable variability still exists in these reactions that is not readily mechanistically rationalized. 

The regioselectivity of nucleophilic addition is a function of the type of nucleophile employed and in many instances can be controlled to give Michael addition to the /3 carbon. 

Other tethers have been employed in the search for regioselectivity in multiple additions to fullerenes. Some of these methodologies include the use of bis(o-quinodimethanes) connected by a, oo-dioxamethylene tethers [40], tethered nucleophilic vinylcarbenes [41] or azides [42],... 

In contrast, the addition of amines results in nucleophilic addition/elimination at the opposite a-position, resulting in substitution of the a-oxygen substituent, a reaction consistent with the Fischer carbene character embedded into this architecture (Equation 2) <2004JOM2000>. This regioselectivity difference almost certainly arises from the reversible nature of addition reactions using such weakly nucleophilic reagents. 

A series of papershave examined the regioselectivity of nucleophilic addition to the arene ligands in a range of [Fe(Cp)(T7 -arene)] cations. The relative distribution of 0-, m-, p-, and ipso-addition products was explained as arising from a combination of electronic, steric, and free valency effects. The nature of the nucleophile was also seen to be important, as shown by the different product distributions obtained from the additions of hydride, cyanide, and acetonyl anions, respectively. 

Surprisingly, even allyl alcohol undergoes the allylation of aldehydes in the presence of 2 mol % of PdCl2(PhCN)2 and 3 equiv of tin(n) dichloride in DMI (Scheme 7)3 ° " The reaction is compatible with aUcyl bromide, aryl bromide, and allyl acetate functionality. The reactivity order of allylic system is allylic carbonate > allylic alcohol > allylic acetate. Un-symmetrical allylic alcohols regioselectively undergo nucleophilic addition at the allylic termini with the highest number of substituent. Generally, anh-isomers are produced preferentially over iyn-isomers. 

In 1991, Pattenden exploited the inherent regioselectivity of nucleophilic additions on P-methoxy maleic anhydrides to prepare gomphidic acid (30) by two different routes (Scheme 1.10) [63]. The first one involves an HWE reaction between phosphonate 80 and aryl pyruvate 81 [63b], and the second one is based on a Reformatsky-type reaction of 77 with zinc enolates derived from aryl acetate 79 [63cj. 

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