Mechanism of nucleophilic substitution at silicon: kinetic evidence on the slow formation of a pentacoordinate silicon intermediate

Kinetic studies of various coupling reactions between silicon derivatives (SiF, SiCl, SiOMe, SiH) and organometallic reagents (RMgX, RLi) were performed for systems involving retention and inversion of configuration. The results show that for both stereochemical courses, the rupture of the SiX bond is not the rate determining step. Results are in good agreement with the rate determining formation of a pentacoordinate silicon intermediate.     

Tautomeric equilibrium between penta- and hexacoordinate silicon chelates. A chloride bridge between two pentacoordinate silicons.

The reaction of O-trimethylsilyl-1,1-dimethyl-2-trifluoroacetylhydrazine (1a) with chloromethyl(methyl)dichlorosilane affords an unexpected equilibrium mixture, 10a right arrow over left arrow 11a, between a neutral hexacoordinate silicon chelate with a covalent chloro ligand (10a) and an ionic pentacoordinate silicon complex (11a). The equilibrium reaction consists formally of a migration of the covalent chloro ligand from silicon to an adjacent ammonium nitrogen, as a chloride anion, and thus constitutes a novel type of tautomeric reaction. Crystallographic and NMR data provide evidence for the reaction. Temperature, solvent, substituent, and counterion effects on the tautomeric equilibrium are discussed: when the temperature of the mixture is raised, the equilibrium ratio 10a/11a increases. Formation of the mixture in toluene, a nonionizing solvent, shifts the equilibrium completely toward the neutral 10a. When the initial hydrazide has a phenyl (11c) or a hydrogen (11b) group as substituent, rather than CF3, the equilibrium is shifted to the ionic side. Replacement of the chloride counterion by triflate, using trimethylsilyl triflate, shifts the 10a/11a mixture to the ionic side. Low-temperature NMR monitoring of the stepwise formation of 10/11 was carried out and provided insight into the reaction mechanism. In an attempt to grow crystals of 11c, the pentacoordinate tautomer analogue, an unprecedented chloride-bridged disiloxane complex, with two pentacoordinate silicons sharing a common axial chloro ligand, crystallized and was characterized and described.     

Chemical bonding in isolated molecules and crystals of zwitterionic pentacoordinate silicon chelates

The electronic structures of a number of zwitterionic pentacoordinate silicon chelates were investigated using the results of X-ray diffraction studies and quantum-chemical calculatoins by the MPW1PW91/6-311G(d) method. The topological analysis of the electron density distribution function and the study in the framework of the natural bond orbital partitioning scheme showed that the character of chemical bonding in the axial fragments of the molecules under consideration changes from dative to three-center, four-electron as the silicon atom assumes a trigonal-bipyramidal coordination.     

Electrophilic catalysis in nucleophilic substitution reactions in ionic liquids

2-Chlorotropone was obtained from 2-tosyloxytropone in 88% yield in the recyclable ionic medium BMIMBF₄/LiCl. That Li⁺ acts as a Lewis acid was proven by the lack of reactivity of 2-tosyloxytropone, under the above conditions, on replacing LiCl with NaCl or BMIMCl, or using BMIMCl alone, or a BMIMBF₄/MeCN/KCl mixture. 2-Bromo- and 2-iodotropone were obtained along similar lines from LiBr or LiI, respectively, whereas LiF proved unreactive.     

Counter-ion effect in the nucleophilic substitution reactions at silicon: a G2M(+) level theoretical investigation

Three identity nucleophilic substitution reactions at tetracoordinated silicon atom with inversion and retention pathways: Nu + SiH₃Cl → Nu + SiH₃Cl[Nu = (1)Cl⁻, (2) LiCl, and (3) (LiCl)₂], are investigated using the G2M(+) theory. Our results show that changing the nucleophile can shift the mechanism (favorable pathway), stepwise from a single-well PES for reaction 1, via a double-well PES for reaction 2, to a triple-well PES for reaction 3, indicating the importance of steric and electronic effects on the S_N2@Si. Electronic Supplementary Material The online version of this article (doi:) contains supplementary material, which is available to authorized users.     

tert-Alcohol-functionalized imidazolium ionic liquid: catalyst for mild nucleophilic substitution reactions at room temperature

Encouraged by a synergistic effect on nucleophilic fluorination, an imidazolium mesylate salt (1a) possessing two different solvent properties in one molecule—tert-alcohol and ionic liquid was utilized in various nucleophilic substitution reactions. By a comparison study with 1-n-butyl-3-methylimidazolium ionic liquids, 1a has proved to be a better phase transfer catalyst even under room temperature conditions. It was successfully applied to other nucleophilic substitution reactions such as fluorination, chlorination, bromination, iodination, acetoxylation, azidation, and cyanation.     

Significantly enhanced reactivities of the nucleophilic substitution reactions in ionic liquid

We have investigated the reactivities of various metal fluorides in the nucleophilic fluorination of 2-(3-methanesulfonyloxypropyl)naphthalene (1) as a model compound in the presence of 1-n-butyl-3-methylimidazolium tetrafluoroborate ([bmim][BF(4)]). The higher periodic alkali metal fluorides demonstrate greater reactivity. The fluorination using CsF among the alkali metal fluorides was completed in 20 min, affording the desired product 2-(3-fluoropropyl)naphthalene (2a, 95%) without any byproducts. However, the fluorinations using alkali earth, transition, and low periodic alkali metal fluorides under the same conditions occurred rarely or not at all. We have also carried out the various facile nucleophilic substitutions such as halogenations, acetoxylation, nitrilation, and alkoxylations of mesyloxyalkane 1 and 2-(3-bromopropyl)naphthalene (6) at the primary aliphatic position using the potassium halides, acetate, cyanide, and alkoxides, respectively, in the presence of ionic liquids. These reactions provided the desired products, such as 2-(3-halopropyl)naphthalenes 5-7 (95% for Cl, 96% for Br, and 93% for I), 2-(3-acetoxypropyl)naphthalene (8, 95%), 2-(3-cyanopropyl)naphthalene (9, 93%), and 2-(3-methoxypropyl)naphthalene (10, 92%).     

Calixarene ionic liquids: excellent phase transfer catalysts for nucleophilic substitution reaction in water

The first examples of calixarene ionic liquids 3 and 6 with 3D-shaped cavities were obtained in high yields by reacting calix[4]arene or thiacalix[4]arene with 1,6-dibromohexane and then refluxing in 1-methylimidazole. The experiments of phase transfer catalysis in water suggested that they possessed excellent catalytic properties of aromatic nucleophilic substitution reaction and benzyl nucleophilic substitution. The optimized yields of product in catalytic reaction were as high as approximate 97% under mild reaction conditions. The cavities of calixarene skeleton played the crucial roles in catalysis and the stable cone conformation was favorable for catalysis.     

Stereospecific nucleophilic substitution at tertiary and quaternary stereocentres

Nucleophilic substitution reactions have always been considered as one of the most powerful reactions for the creation of carbon–carbon or carbon–heteroatom bonds in organic synthesis. In contrast to secondary carbons, the steric shielding of tertiary carbons retards a concerted, stereospecific nucleophilic substitution, and ionizing pathways often lead to nonselective substitution due to ion pair dissociation. In this minireview, we will detail pioneering contributions and more recent achievements emphasizing the feasibility of nucleophilic substitution on tertiary stereocentres under certain conditions, with inversion of configuration. The development of these transformations at tertiary centres are of remarkable added value to practitioners in the field of complex molecule synthesis. A stereoselective substitution at a quaternary carbon stereocentre with inversion of configuration is also discussed in the case of a three-membered ring.

In this minireview, we summarized the fascinating and rich area of stereoselective or stereospecific nucleophilic substitution at tertiary and quaternary carbon centres.     

Mono- and dialkylations of pyrrole at C2 and C5 positions by nucleophilic substitution reaction in ionic liquid

[reaction: see text] A novel ionic liquid methodology for pyrrole C-alkylation is described. The pyrrole alkylation is achieved with various simple alkyl halides and mesylates selectively at C2 and C5 positions in good yields with minimal byproducts under relatively mild conditions in various ionic liquids. 2-(3-Phenylpropyl)pyrrole (2a) was synthesized from pyrrole and 1-bromo-3-phenylpropane in a mixture solvent system, [bmim][SbF6] and CH3CN, in 81% yield at 115 degrees C for 44 h with 5% yield of dialkylated compound 3a.     

Polymer-supported protic functionalized ionic liquids for nucleophilic substitution reactions: superior catalytic activity compared to other ionic resins

Three polymer-supported quaternary ammonium mesylates were synthesized for recyclable polymeric phase transfer catalysts (PTCs). Through comparison study using nucleophilic fluorination, tertiary alcohol containing polymer 3c proved to be the best catalyst with high catalytic activity and chemoselectivity. It also exhibited not only superior activity in other nucleophilic substitution reactions, such as chlorination, bromination, iodination, acetoxylation, and azidation, but also good recyclability without any loss of catalytic activity or product yield.     

The mechanism of nucleophilic substitution at silicon. Action of organometallic reagents on chiral bifunctional silanes

The study of nucelophilic substitution of monofunctional organosilanes has been extended to bifunctional derivatives. The reactions are both selective and stereoselective. Our results can be interpreted in terms of leaving group polarisability and the softness/hardness of the attacking nucleophile.The presence of two electronegative substituents only slightly modifies the stereochemistry. A pseudorotation mechanism could not explain the retention observed in certain cases. We envisage two possible modes of attack, either with axial or equatorial entry, leding respectively to inversion or retention at the silicon atom.     

Efficient nucleophilic substitution reactions of highly functionalized allyl halides in ionic liquid media

Nucleophilic substitution reactions of highly functionalized allyl halides with three anions, N₃⁻, AcO⁻, and PhSO₂⁻, in ionic liquid media were conducted. The ionic liquid, [Bmim][BF₄], was found to be superior to classical organic solvents to give higher yields and faster reaction rates. The resulting products belong to multifunctionalized trisubstituted α,β-unsaturated ketones, which are useful building blocks for organic synthesis.     

Theoretical study of nucleophilic substitution at sulfur in sulfinyl derivatives

A series of gas-phase nucleophilic substitution reactions at sulfur of methanesulfinyl derivatives by small anions (chloride, cyanide, hydroxide, methoxide, amide, and phosphide, identical to the leaving group in each case) were examined by Hartree-Fock, MP2, and DFT computations. In most cases, substitution was found to follow an addition-elimination mechanism, resulting in a triple-well potential energy surface with small barriers of activation on either side of the central, tetracoordinate-sulfur minimum. The geometries of the central minima, as in the analogous methanesulfenyl cases, are unsymmetrical trigonal bipyramidal, with the nucleophiles and leaving groups occupying apical positions and the sulfur lone pair an equatorial position. The apparent exception, cyanide, may undergo an S(N)2 displacement.     

Secondary kinetic isotope effect in nucleophilic substitution: a quantum-mechanical approach

Four-dimensional time-independent quantum scattering calculations have been carried out on the perdeuterated exothermic and complex-forming gas-phase S(N)2 reaction Cl- + CD3Br --> ClCD3 + Br- and the reverse process Br- + CD3Cl --> BrCD3 + Cl-, employing a fine energetic resolution to resolve all scattering resonances. The two totally symmetric modes of the methyl group, C-D symmetric stretch and umbrella bend, are explicitly taken into account. Converged state-selected reaction probabilities and product distributions have been calculated up to 2960 cm(-1) above the vibrational ground state of CD3Br, i.e., up to initial vibrational excitation of the second overtone of the umbrella bending vibration. The inverse secondary kinetic isotope effect found experimentally is nicely confirmed by the calculated state-selected reaction probabilities. One contribution to this originates from excitation of the high-frequency symmetric C-D stretching vibration, which increases the reaction probability as a function of translational energy more than the corresponding vibration in the undeuterated system. Although transition state theory (TST) suffices to explain this effect qualitatively, the dynamics of S(N)2 reactions is well-known to show strong nonstatistical features. A striking example is given by the umbrella mode: Contrary to estimates obtained from TST, we find a significant enhancement of the reactivity in the perdeuterated system that is attributed to the increased density of states and the higher number of avoided crossings of the hyperspherical adiabats compared to the undeuterated system. Furthermore, compared to the system Cl- + CH3Cl'/CD3Cl', the influence of tunneling is negligible in this net-barrierless reaction. In the reverse endothermic reaction, the kinetic isotope effect of the umbrella mode is normal.