Pyridine soft nucleophile

However, if we look at the LUMO, we find that it has the form 4.65, namely that of ift4 of benzene, but polarised by the nitrogen atom. This polarisation has reduced the coefficient at C-3, and the coefficient at C-4 is larger than that at C-2, as can be seen from the simple Hiickel calculation for pyridine itself in Fig. 4.11, which gives LUMO coefficients of 0.454 and —0.383, respectively, and an energy of 0.56/3 (compare benzene with 1/3 for this orbital). Thus, soft nucleophiles should attack at C-4, where the frontier orbital term is largest. Again this is the case cyanide ion, bisulfite, enolate ions, and hydride delivered from the carbon atom of the Hantsch ester 4.67 react faster at this site. 

Reaction with P-Donors. In accord with the expectations dis-cussed above, Cp2Mo2(C0K reacts readily with two equivalents of soft nucleophiles, e.g., phosphines, phosphites, CO, etc., to give exclusively the trans-products indicated in eq. 7. With one equivalent of ligand, only disubstituted product (1/2 equiv.) and unreacted 1 (1/2 equiv.) are isolated. Hence, the addition of the first ligand is the slow step (eq. 18). Complex 1 does not react with hard bases, e.g., aliphatic amines, pyridine, ethers, alcohols, or ketones. Bulky phosphines, e.g., (cyclohexyl)3P, and Ph3As or Ph3Sb also fail to react at room temperature. Rather... 

The reactions of HNCC with soft nucleophiles (CO, PR3, RCCR, RjCCRj, pyridine, NOj, and halides) result either in the formation of addition or substitution products, or in cluster breakdown. The nature of the species formed depends on the nucleophile (which may or may not undergo transformation on the cluster surface), the type of metal cluster, and the conditions employed in the reaction. Generally, clusters of the lighter elements tend to fragment even under mild conditions, while those of the heavier elements, which are more robust, often afford addition and substitution products. 

In a series of outstanding papers, Pinhey et al have shown that aryllead tricarboxylates react with soft nucleophiles to afford C-arylation products. These aryllead derivatives behave as aryl cation equivalents in reactions which involve a ligand coupling mechanism (see section 7.5).9 2 ju most cases, the reactions proceed in chloroform at 40-60 C in the presence of pyridine as a base with a ratio of substrate to organolead derivative to pyridine of 1 1 3. The substrates which easily undergo C-arylation include phenols, p-dicarbonyl compounds and their vinylogues, a-cyanoesters, a-hetero-substituted ketones, enamines and nitroalkanes. A very limited number of non-carbon nucleophiles has also been reported to react. 

All the halo-diazines, apart from 5-halo-pyrimidines, react readily with soft nucleophiles, such as amines, thiolates and malonate anions, with substitution of the halide. Even 5-bromopyrimidine can be brought into reaction with nucleophiles using microwave heating. All cases are more reactive than 2-halo-pyridines the relative reactivities can be summarised ... 

Other additions. 4-Substituted dihydropyridines are usually synthesized by addition reactions on activated pyridines. Derivatization of 3-pyridinecarbalde-hyde into a C2-symmetrical imidazolidine enables the addition enantioselective by using soft nucleophiles, the attack of which is preceded by coordination to the chiral auxiliary. 

Soft nucleophiles (X = CN , SCN , 1 ) attack Ni(5-C1CH2- or 5-HOCH2-ODC) at C-10 to give Ni(5-Me-10-X-ODC), white 5 2 reactions occur with hard nucleophiles (HO , CF3C02 ). Oxidation of natural cobalt(III) corrins by KMuO -pyridine gives 5- or 15-carboxy and 5,I5-di-carboxy derivatives. Acetoxylation of the meso methyl groups has also been reported. ... 

The molybdenum and tungsten complexes catalyze reactions of soft nucleophiles, such as malonates, related 1,3-dicarbonyl compoimds, and nitroalkanes. Azlactones are also soft carbanions, and Trost has shown that complexes formed from molybdenum and the bis(pyridine) ligands catalyze enantioselective and diastereoselective allylation of azlactones with allylic phosphates to form quaternary amino acids (Equation 20.40). In these reactions, the nucleophile adds to the more substituted position of the allylic electrophile, and a stereocenter is formed at both the allyl carbon and the azlactone carbon. One route to the protease inhibitor tipranavir by the molybdenum-catalyzed allylation with 1,3-dicarbonyl compounds was demonstrated by Trost (Equation 20.41), and the Merck process group used related allylation chemistry with Trost s bis(pyridine) ligand to prepare the cyclopentanone precursor to various analogs of tipranavir (Equation 20.42). 

One possible solution of this problem is to differentiate a radical first as electrophilic or nucleophilic with respect to its partner, depending upon its tendency to gain or lose electron. Then the relevant atomic Fukui function (/+ or / ) or softness f.v+ or s ) should be used. Using this approach, regiochemistry of radical addition to heteratom C=X double bond (aldehydes, nitrones, imines, etc.) and heteronuclear ring compounds (such as uracil, thymine, furan, pyridine, etc.) could be explained [34], A more rigorous approach will be to define the Fukui function for radical attack in such a way that it takes care of the inherent nature of a radical and thus differentiates one radical from the other. 

Swain and Scott found satisfactory correlations with Equation (27) which provided 5 values for a number of reactants. However, as indicated in Scheme 33, for the limited number of substrates conveniently studied,158,186 variations in 5 did not show a clearly discernible pattern (and no obvious correlation with reactivity). Moreover, Pearson and Songstad demonstrated that the correlations break down if extended to extremes of soft and hard electrophilic centers such as platinum, in the substitution of trara,s-[Pt(pyridine)2Cl2], or hydrogen in proton transfer reactions.255 Despite this, Swain and Scott s equation has stood the test of time and it is noteworthy that a serious breakdown in the correlations occurs only when the reacting atoms of both nucleophile and electrophile are varied. In this chapter we will restrict ourselves to carbon as an electrophilic center, and particularly, although not exclusively, to carbocations. 

Also, operating at 200°C tlie reaction occurs at the carbonyl atom only. In fact, when 1-octanol was used in reactions with DMC in the presence of K2CO3, no methyl ether was observed, but methyl octyl carbonate and dioctyl carbonate were the only products formed. Methylation of alcohols was reported to occur also operating in the presence of tertiary amines (N,N -dimethylamino-pyridine, l,4-diazobicyclo[2,2,2]octane). In this case, however, the catalyst modifies the hard-soft character of the two centers, thus allowing the nucleophilic displacement by the alkoxide to occur. 

Being anionic carbonyl synthons, the nitroalkanes have been explored extensively for their conversion into the corresponding carbonyl compounds. For example, the embedment of a nitroalkane onto an activated basic silica gel or the blockage of the C-protonation of nitronate with a protonated concave pyridine. The reaction under the latter condition is called the soft Nef reaction. In addition, the introduction of a y-trimethylsilyl group is proved to smooth the Nef reaction. Moreover, when a primary nitroalkane is treated with nitrite/acetic acid, a carboxylic acid is resolved. Furthermore, the oxidative Nef reaction has successfully converted the nitro cyclohexadienes into the substituted phenols via a nucleophilic addition. 

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