Nitrogen-based nucleophiles

Step 4 DBU (l,8-diazabicyclo[5.4.0]undec-7-ene), a bulky, non-nucleophilic nitrogen base, is used to form the epoxide. 

The reaction of an arylamine with B0C2O in the absence of a nucleophilic nitrogen base leads exclusively to the N-Boc derivative (urethane), as is well-established in protecting group chemistry. The urethane is not an intermediate of the isocyanate synthesis described here, since it does not undergo a reaction with either B0C2O or DMAP alone. 

In addition to carbon nucleophiles, nitrogen-based nucleophiles can be used for the nickel-catalyzed cross-coupling with aryl cyanides in the presence of CsF, the role of which is yet to be clarified (Scheme 13) [55]. Silylphosphines are reported to... 

The nucleophilic attack of nitrogen bases leads to a variety of products as the result of addition or addition-elimination reactions The regioselectivity resembles that of attack by alcohols and alkoxides an intermediate carbanion is believed to be involved In the absence of protic reagents, the fluorocarbanion generated by the addition of sodium azide to polyfluonnated olefins can be captured by carbon dioxide or esters of fluonnated acids [J 2, 3] (equation I)... 

The initiating nucleophile in the vast majority of these studies is the hydroxide anion. However, in principle, any nucleophile can add to the keto or formyl group to give rise to an anionic intermediate, which then could act as an intramolecular nucleophile and effect hydrolysis of the ester. Their relative effectiveness will depend on two factors the relative extent of formation and the nucleophilicity of the adduct. The nucleophiles that have been investigated are hydroxide, cyanide, morpholine and piperazine. The only quantitative comparison available is that of hydroxide, morpholine and piperazine, which are effective in the order of ca. 102 10-3 1 (Bender et al., 1965 Dahlgren and Schell, 1967). For morpholine and piperazine this is as expected on the basis of their relative basicities. However, the expected order of increasing formation of the adducts would be cyanide > nitrogen bases > hydroxide (Hine, 1971). At this time, these results cannot be analysed further, but more work on the systems could enable the structural dependence and reactivity to be elucidated. 

In the case of the experiments performed by Hohman and co-workers [149], the fluoride anion would readily displace the silicon-leaving group. The peroxide anion could then further react via an intramolecular nucleophilic attack, resulting in cyclization to form the reactive intermediate responsible for the chemiluminescence that was observed. A recent kinetic study by Stevani and Baader [150] of the reaction of 4-chlorophenyl-O,O-hydrogen monoperoxyoxalate with various oxygen and nitrogen bases suggested that the intermediate formed must be 1,2-dioxetandione. 

An ab initio MO study has been carried out on a linear relationship between free energies of activation of Menshutkin reactions and the proton affinities of the nitrogen bases used as nucleophiles. The relationship had been discovered some... 

Concerning the mechanism of the rearrangement, it is proposed to involve the addition of the nucleophilic nitrogen of the 1,3-ambident nucleophiles to C-6 (see Section III,A,2,a). This covalent adduct is in equilibrium with the open-chain diamidino compound 83 (R = OCH3, SCH3). Cycliza-tion into 84, followed by a base-catalyzed fragmentation of the nitrogen-carbon bond at N-3 and expulsion of the thiomethyl or methoxy anion, yields the 2-amino-4(5)-phenylpyrimidines (Scheme III.47). 

The first class of amine-based nucleophilic catalysts to give acceptable levels of selectivity in the KR of aryl alkyl. yec-alcohols was a series of planar chiral pyrrole derivatives 13 and 14, initially disclosed by Fu in 1996 [25, 26]. Fu and co-workers had set out to develop a class of robust and tuneable catalysts that could be used for the acylative KR of various classes of. yec-alcohols. Planar-chiral azaferrocenes 13 and 14 seemed to meet their criteria. These catalysts feature of a reasonably nucleophilic nitrogen and constitute 18-electron metal complexes which are highly stable [54-58]. Moreover, by modifying the substitution pattern on the heteroaromatic ring, the steric demand and hence potentially the selectivity of these catalysts could be modulated. 

Based on the observation that the majority of secondary amines shown to be effective in iminium ion catalysed transformations were cyclic five-membered nitrogen containing heterocycles, it was postulated that a highly nucleophilic nitrogen was central to catalytic activity [44]. This proposal was reinforced by the discovery that secondary amines with a-heteroatoms (a-effect nucleophiles) provided an effective platform for the acceleration of iminium ion catalysed... 

Application of an organocatalytic domino Michael addition/intramolecular aldol condensation to the preparation of a series of important heterocycles has recently received much attention [158] with methods being disclosed for the preparation of benzopyrans [159-161], thiochromenes [162-164] and dihydroquinolidines [165, 166]. The reports all use similar conditions and the independent discovery of each of these reactions shows the robust nature of the central concept. A generalised catalytic cycle which defines the principles of these reports is outlined in Fig. 10. Formation of iminium ion 102 is followed by an intermolecular Michael addition of an oxygen, sulfur or nitrogen based nucleophile (103) to give an intermediate... 

Wrapping up the nitrogen-based nucleophiles, aromatic amines were also noted to cleave epoxides in the presence of stannic or cupric triflate to form p-amino alcohols such as 86 directly. This protocol appears to be general for aromatic amines, even strongly electron-deficient ones. Aliphatic amines are completely unreactive under the same experimental conditions <99JOC287>. 

Nucleophilic attack on a nitrile rather than a carbonyl has also provided aminopyrimidines as reported by Hassanien and co-workers in their efforts to discover new sulfonamide drugs <99JCR(S)8>. The reactions of sulfonamides 12 with a variety of nitrogen-based nucleophiles produced aminopyrimidines 13. 

The mechanism of the thermal ROP of (Cl2PN)3 has been proposed to involve a cationic mechanism (see Scheme 8.2 in Section 8.1.2.2). The unique reaction sequence involving ROP followed by nucleophilic substitution with oxygen- or nitrogen-based nucleophiles (generally alkoxides, aryloxides or primary amines) permits a diverse range of polyorganophosphazenes to be... 

Nucleophilicity. A distinction is usually made between nucleophilicity and Lowry-Bronsted basicity [213]. The latter involves specifically reaction at a proton which is complexed to a Lewis base (usually H2O), while the former refers to reactivity at centers other than H. Linear correlations have been shown for gas-phase basicity (proton affinity) and nucleophilicity of nitrogen bases toward CH3I in solution [214] where the solvent is not strongly involved in charge dispersal. In each case, reaction of the base/nucleophile... 

Some examples of the behavior of unsaturated ketonucleosides under alkaline conditions have also been reported. The enol acetate 61a is more stable than the parent ketonucleoside 36a. In 0.1 M methanolic sodium hydroxide, free theophylline was detected only after 4 h, by which time, loss of the acetyl group was complete a reaction time of more than 18 h was needed for complete cleavage of the glycosylic bond.51 In alcoholic solution, the unsaturated 4 -ketonucleoside 66 was very sensitive to nucleophilic attack, and decomposed rapidly, with elimination of the nitrogenous base.31 Thus, treatment with sodium borohydride at — 70° led to complete decomposition within 10 min but, when sodium borohydride was added to a solution of 66 in 1,2-dichloroethane containing acetic acid, fast reduction occurred, and no degradation was observed.31... 

The magnitude of general-acid-base catalysis by oxygen and nitrogen bases depends only on their pATa s, and is independent of their chemical natures (apart from an enhanced activity of oximes in general-acid catalysis). Nucleophilic reactivity depends markedly on the nature of the reagents. These reactions may be divided into two broad classes nucleophilic attack on soft and on hard electrophilic centers.47... 

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