Nucleophilic addition reactions regioselectivity

The attack of the nucleophile on the acceptor-substituted allene usually happens at the central sp-hybridized carbon atom. This holds true also if no nucleophilic addition but a nucleophilic substitution in terms of an SN2 reaction such as 181 — 182 occurs (Scheme 7.30) [245]. The addition of ethanol to the allene 183 is an exception [157]. In this case, the allene not only bears an acceptor but shows also the substructure of a vinyl ether. A change in the regioselectivity of the addition of nucleophilic compounds NuH to allenic esters can be effected by temporary introduction of a triphenylphosphonium group [246]. For instance, the ester 185 yields the phos-phonium salt 186, which may be converted further to the ether 187. Evidently, the triphenylphosphonium group induces an electrophilic character at the terminal carbon atom of 186 and this is used to produce 187, which is formally an abnormal product of the addition of methanol to the allene 185. This method of umpolung is also applicable to nucleophilic addition reactions to allenyl ketones in a modified procedure [246, 247]. 

An alternative stereoselective synthesis of chiral heterocycles based on carbohydrate-induced stereodifferentiation includes nucleophilic addition reactions on heterocyclic systems already bound to the carbohydrate auxiliary. An example of this strategy has been shown by stereoselective addition of Grignard reagents to carbohydrate-linked 4-pyridones [61]. For this purpose, trimethylsiloxypyridine was glycosylated regioselectively using pivaloyl-protected glycosyl fluorides. 

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. 

The Tt-allyl ligand bonded to transition-metal cations can be susceptible to nucleophilic addition reactions either on a terminal or on the central carbon atom. Regioselec-tive addition to a terminal carbon of an allyl ligand produces a metal-tt-olefin complex (see 5.8.2.3.10), whereas regioselective addition to the central carbon leads to metallacyc-lobutane formation ... 

Scheme 2.3 summarizes the regioselectivity of nucleophilic addition reactions on the A ring of estradiol derivatives modified by incorporation of a cationic manganese tricarbonyl group [97]. 

NUCLEOPHILIC ADDITION REACTIONS TO ARYNES 12.5.1 Regioselectivity Issues for Functionalized Arynes... 

The nucleophilic addition reactions of the (ii -2-methylbutadiene) complexes [CpMo(CO)2(Tl -CH2=CMeCH=CH2)] [PF6l with alkyllithium and Grignaid reagents has been shown227 to have a regioselectivity which is solvent-dependent... 

The proposed biosyntheses of ether-containing natural products employ enzymes to introduce epoxide groups with complete stereocontrol and, in some cases, to dictate the regioselectivity of the nucleophilic addition reactions. Chemical mimicry of these pathways reqnires extensive understanding of the fundamental structural relationships for epoxide reactivity toward tetherednucleophiles. Additionally,... 

Wong et at, and showed PCE of 5.9% on the P3HT-based BHJ OSCs. An alternative method to obtain a single regioisomer has been proposed by us, with a regioselective nucleophilic addition reaction to Cgo and In this... 

Recently it has been demonstrated that the methodology can also be used on ( )-W-(pyridin-2-ylmethylene)-based substrates wherein it involves the addition of the nucleophile across the imino C=N bonds with diastereoselectivities up to 1 20 in favor of the S isomer (Scheme 14) [71, 72]. The presence of the imino nitrogen in this instance is the predominating electronic factor which dictates the regioselectivity of the nucleophilic addition reaction and leads to the exclusive generation of the five-membered chelate. 

A synthetically useful diastereoselectivity (90% dc) was observed with the addition of methyl-magnesium bromide to a-epoxy aldehyde 25 in the presence of titanium(IV) chloride60. After treatment of the crude product with sodium hydride, the yy -epoxy alcohol 26 was obtained in 40% yield. The yyn-product corresponds to a chelation-controlled attack of 25 by the nucleophile. Isolation of compound 28, however, reveals that the addition reaction proceeds via a regioselective ring-opening of the epoxide, which affords the titanium-complexed chloro-hydrin 27. Chelation-controlled attack of 27 by the nucleophile leads to the -syn-diastereomer 28, which is converted to the epoxy alcohol 26 by treatment with sodium hydride. 

Another interesting example is provided by the phenylethynylcarbene complex 173 and its reactions with five-, six-, and seven-membered cyclic enamines 174 to form bridgehead-substituted five-, six-, and seven-membered cycloalkane-annelated ethoxycyclopentadienes with high regioselectivity under mild reaction conditions (Scheme 38) [119,120]. In these transformations the phenylethynylcarbene complex 173 acts as a C3 building block in a formal [3+2] cycloaddition. Like in the Michael additions (reaction route F in Scheme 4), the cyclic electron-rich enamines 174 as nucleophiles attack the... 

The possible reaction pathways for the stereoselective E- and Z-allylation are illustrated in Scheme 7. 1-Silyl-l,3-dienes 22 react with a Ni-H species in the presence of PPI13 to provide a syn-it-allylnickel species 24, the least substituted allylnickel species, which undergoes nucleophilic addition to an aldehyde at the least substituted allylic terminus to provide ( )-allylsilanc ( )-23. It should be noted that the regioselectivities observed for the Ni-H addition to a diene 22 and nucleophilic addition of 24 to aldehydes are opposite to those observed so far in many precedents in this review (e.g., Eqs. 4 and 6). 

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