Nucleophilic substitution products

The Pd—C cr-bond can be prepared from simple, unoxidized alkenes and aromatic compounds by the reaction of Pd(II) compounds. The following are typical examples. The first step of the reaction of a simple alkene with Pd(ll) and a nucleophile X or Y to form 19 is called palladation. Depending on the nucleophile, it is called oxypalladation, aminopalladation, carbopalladation, etc. The subsequent elimination of b-hydrogen produces the nucleophilic substitution product 20. The displacement of Pd with another nucleophile (X) affords the nucleophilic addition product 21 (see Chapter 3, Section 2). As an example, the oxypalladation of 4-pentenol with PdXi to afford furan 22 or 23 is shown. 

A unimolecular ionization was shown to be the mechanism of solvolysis by means of rate studies, solvent effects, salt effects, and structural effects (179,180). The products of reaction consist of benzo [bjthiophen derivatives 209 or nucleophilic substitution products 210, depending upon the solvent system employed. By means of a series of elegant studies, Modena and co-workers have shown that the intermediate ion 208 can have either the open vinyl cation structure 208a or the cyclic thiirenium ion 208b, depending... 

In n-CsHl3. No solvent. Plus nucleophilic substitution products. 

When pure (+H5)-167 was reacted with potassium p-cresylate, sodium amide, and dimethylamine, the corresponding nucleophilic substitution products 169,170, and 171 were formed (Scheme 14). In each case, complete or almost complete inversion of configuration at chiral sulfur was observed. 

The yield of the nucleophilic substitution product from the stepwise preassociation mechanism k[ = k. Scheme 2.4) is small, because of the low concentration of the preassociation complex (Xas 0.7 M for the reaction of X-2-Y). Formally, the stepwise preassociation reaction is kinetically bimolecular, because both the nucleophile and the substrate are present in the rate-determining step ( j). In fact, these reactions are borderline between S l and Sn2 because the kinetic order with respect to the nucleophile cannot be rigorously determined. A small rate increase may be due to either formation of nucleophile adduct by bimolecular nucleophilic substitution or a positive specific salt effect, whUe a formally bhnole-cular reaction may appear unimolecular due to an offsetting negative specific salt effect on the reaction rate. 

The change from a stepwise preassociation mechanism through a triple ion intermediate to an uncoupled concerted reaction occurs as the triple ion becomes too unstable to exist in an energy well for the time of a bond vibration ( 10 s). The borderline between these two reaction mechanisms is poorly marked, and there are no clear experimental protocols for its detection. These two reaction mechanisms cannot be distinguished by experiments designed to characterize their transition states, which lie at essentially the same position in the inner upper right hand corner of Figure 2.3. Only low yields of the nucleophilic substitution product are obtained from both stepwise preassociation and uncoupled concerted reactions, because for formation of the preassociation complex in water is small... 

The first synthesis1121 of A -foi-BocHN-alky]) amino acid building units used nucleophilic substitution of a-halocarboxylic acids or their esters 30 (Scheme 18) with mono-Boc-sub-stituted diamines 29. The nucleophilic substitution product 31 was reacted with Fmoc-OSu to give the orthogonally protected building unit 32. 

Treatment of 1-chloronapthalene with ethoxide ion gives no reaction. Treatment of 5 with ethoxide, however, gives the nucleophilic substitution product shown in Equation 9. Explain the difference in behavior between 1-chloronapthalene and 5. 

Aromatic nucleophlic substitution with stabilized carbanions is possible, and nucleophilic substitution products and cyclohexadiene derivatives are preparable. 

Flash chromatography has been applied to study the vicarious nucleophilic substitution products of nitroazoles (pyrazoles, imidazoles, indazoles, and benzimidazoles) [319], the thermal isomerization of the nitroisoxazoles into nitrooxazoles (with petroleum ether/ethyl acetate 10 1 v/v as eluent) [501, 502],... 

The 5 -0-tosyl derivative of cytidine 227, upon reaction with KF and an azocrown ether, gave, unexpectedly, instead of the nucleophilic substitution product, the oxazocine 228 via nucleophilic attack by the 2-carbonyl oxygen initiated by proton abstraction from N-4 by fluoride (Scheme 46) <1998BML1317>. 

When the same carbodiimide is heated with 3-substituted l-phenylpyrazol-5-ones 50 in the presence of triethylamine the initially formed nucleophilic substitution product 51 undergoes cyclization to give 6-aryl-4-arylimino-l-phenyl-6-trifluoromethyl-1,4,5,... 

All of these reactions are nucleophilic substitutions and have the same overall result— replacement of the leaving group by the nucleophile, regardless of the identity or charge of the nucleophile. To draw any nucleophilic substitution product ... 

Acid chlorides readily react with nucleophiles to form nucleophilic substitution products,... 

Decreasing the solvent polarity is an effective strategy to decrease the amount of MgX-LG exchange and reduction reactions. Two potential explanations are a decrease in the solubility of MgX2-THF , or a shift in the Schlenk equilibrium (see Chapter 13). Subsequently, there are no Lewis acid sites in solution that could catalyze these competing reactions. For example the addition of toluene as a cosolvent can take a reaction that predominately undergoes reduction [80%, see Eq. (50)] to yield the nucleophilic substitution product [75% Eq. (61) 151]. 

Under acidic as well as under basic conditions 1-dialkylaminocyclopropanols, 1-alkoxycyclo-propanols, and l,l-bis(dialkylamino)cyclopropanes usually give predominantly nucleophilic substitution products in which the three-membered ring is retained, probably via cyclopropyl cations that are strongly stabilized by resonance with the neighboring heteroatoms, e.g. 1016,34-40 Section l.A.5.2.1.). 

In comparison to the ease of alkoxycarbonylation of halopyrazines, the aminocarbonylation was dramatically influenced by both the phosphorus ligands and carbon monoxide pressure. Pyrazinecarboxamide was prepared via aminocarbonylation using diethylamine as solvent. For example, 2-chloropyrazine was converted into 2-(diethylaminocarbonyl) pyrazine (173) in 85% yield along with 8% of the nucleophilic substitution product 174. Intriguingly, when butylamine was used, the corresponding S Ar product similar to 174 was the major product (72% yield), whereas the amide was isolated as a minor product (28%). 

X Y Ri, R2 R3, R4 Nucleophile Substitution product %I %n Leaving group from (I) Leaving group from (II) Reference... 

When 2-bromo-4,5-dicyano-l-methylimidazole is treated at reflux with 4-dimethylaminopyridine the initial nucleophilic substitution product loses its iV-methyl group because 4,5-dicyanoimidazole anions are such good leaving groups (Scheme 36) <89H(29)I325>. 

Irradiation of primary alkyl bromides or iodides affords typically a mixture of reduction and elimination products. For example, a radical pair produced by photolysis of the halooctanes 469 undergoes in the initial stage either competing diffusion and hydrogen abstraction from the solvent molecules (to give 470) or electron transfer giving rise to elimination product (471) a favoured process in case of alkyl iodides (Scheme 6.229).1336 Formation of the nucleophilic substitution product 472 is not observed, because solvent does not participate in carbocation generation. 

Titration of la with a chloride-sensitive electrode indicates that the initial intermediate is the nucleophilic substitution product, the 3-chlorothiatriazin-5-ol 3. 

It is also appropriate to mention the modern mechanistic work on the very first type of reaction in the chemistry of aliphatic diazo compounds, namely deamination (1-1). In contrast to the 1,3-dipolar cycloadditions deaminations of aliphatic amines are relatively seldom applied for synthetic purposes (see Sect. 7.7), because they lead in most cases to a mixture of nucleophilic substitution products as well as elimination and rearrangement products. It has been clear, at least since the work of Young and Andrews (1944), Ingold s group (Brewster et al., 1950) and others, that, basically, these reactions belong to the class of nucleophilic aliphatic substitutions in spite of a bewildering number of complicating factors (see Chapt. 7). 

Although nucleophilic reactions of the smallest [n]metacyclophane 4a (Structures 1) was not reported, unusual reactivity of its halogen-substituted derivatives 4b-e (Scheme 9, Structures 23) toward nucleophiles was reported by Bickelhaupt [66, 74]. Treatment of chlorocyclophanes 4b and 4e with sodium alkoxide gave nucleophilic substitution products 4f and 4g (Structures 23), respectively, through a S yAr mechanism [74b]. The regioselective substitution at C-11 is explained in terms of (i) greater stability of the Meisenheimer complex... 

Knowledge of the contributions of individual substituents to the conformational preferences of oxocarbenium ions, however, is not sufficient to predict the reactivities of highly substituted systems such as those formed from carbohydrates. [Other intermediates, aside from discrete oxocarbenium ions, could also lead to the nucleophilic substitution products. For an example involving ion-pair intermediate, see Crich et al. [15].] For the type of substrates presented in this work, neither the Lewis acid nor the solvent has significant influence upon product distribution as described in Ref. [19]. For instance, although the influences of the C2, C3, and C4 substituents on the mannopyranosyl cation should reinforce each other to favor P-product, a-selectivity was observed upon allylation of the mannosyl phosphate 29 (Fig. 4.10) [Allylation of maimosyl phosphate 29 has been shown to be highly a-selective with MesSiOTf [67]. C-Mannosylation reactions are generally a-selective [68-76]. a-Selectivity was also observed with acetate-protected... 

The SnCl2-reduction system has also been apphed in the reduetion of S 2 nucleophilic substitution products 583, alfording more functional quinolines, 4-(substituted vinyl)-quinolines 584, in moderate yields, with several exclusions of the formation of dihydroquinoline derivative 585 (Scheme 4.174). However, using compounds 586 as substrates without a ketone moiety, the ester group can also participate in the intramolecular cychzation, but the subsequent dehydrogenation does not occur and, therefore, tetrahydroquinolin-2-ones 587 were obtained in 51-62% yields (frans form only). From this study, the preference of the activated carbonyl group COR for cychzation has the order R = Me > Ph > O-alkyl. 

Irradiation of bridgehead bromides and iodides (RX) in a variety of solvents (SH) results in the formation predominantly of the nucleophilic substitution products (RS) as well as some hydrocarbon (RH), particularly with the bromides. Both radical and heterolytic cleavage of the photoexcited RX molecules are encompassed within the mechanisms discussed. The systems studied include 1-norbornyl, 1-norbornylmethyl, and 1- and 2-adamantyl bromides and iodides. Electrochemical and metal-ammonia reduction of 1,4-dihalogenonorbornanes yields mainly nor-bornane (and not the required [2,2,l]propellane) and some l,r-bisnorbornane. ... 

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