Sterically hindered solutes

The formation of the above anions ("enolate type) depend on equilibria between the carbon compounds, the base, and the solvent. To ensure a substantial concentration of the anionic synthons in solution the pA" of both the conjugated acid of the base and of the solvent must be higher than the pAT -value of the carbon compound. Alkali hydroxides in water (p/T, 16), alkoxides in the corresponding alcohols (pAT, 20), sodium amide in liquid ammonia (pATj 35), dimsyl sodium in dimethyl sulfoxide (pAT, = 35), sodium hydride, lithium amides, or lithium alkyls in ether or hydrocarbon solvents (pAT, > 40) are common combinations used in synthesis. Sometimes the bases (e.g. methoxides, amides, lithium alkyls) react as nucleophiles, in other words they do not abstract a proton, but their anion undergoes addition and substitution reactions with the carbon compound. If such is the case, sterically hindered bases are employed. A few examples are given below (H.O. House, 1972 I. Kuwajima, 1976). 

The ketone is added to a large excess of a strong base at low temperature, usually LDA in THF at -78 °C. The more acidic and less sterically hindered proton is removed in a kineti-cally controlled reaction. The equilibrium with a thermodynamically more stable enolate (generally the one which is more stabilized by substituents) is only reached very slowly (H.O. House, 1977), and the kinetic enolates may be trapped and isolated as silyl enol ethers (J.K. Rasmussen, 1977 H.O. House, 1969). If, on the other hand, a weak acid is added to the solution, e.g. an excess of the non-ionized ketone or a non-nucleophilic alcohol such as cert-butanol, then the tautomeric enolate is preferentially formed (stabilized mostly by hyperconjugation effects). The rate of approach to equilibrium is particularly slow with lithium as the counterion and much faster with potassium or sodium. 

Attention should be paid to the fact that the ratio of Pd and phosphine ligand in active catalysts is crucial for determining the reaction paths. It is believed that dba is displaced completely with phosphines when Pd2(dba)3 is mixed with phosphines in solution. However the displacement is not eom-plcte[16]. Also, it should be considered that dba itself is a monodentate alkene ligand, and it may inhibit the coordination of a sterically hindered olefinic bond in substrates. In such a case, no reaction takes place, and it is recommended to prepare Pd(0) catalysts by the reaction of Pd(OAc)2 with a definite amount of phosphinesflO]. In this way a coordinatively unsaturated Pd(0) catalyst can be generated. Preparation of Pd3(tbaa)3 tbaa == tribenzylidene-acetylacetone) was reported[17], but the complex actually obtained was Pd(dba)2[l8],... 

Both the equilibria and the enhancement of the coefficients can be improved by additives, of which sodium arsenite is the major one in use, but sodium hypochlorite and small amounts of amines also are effective. Sterically hindered amines as promoters are claimed by Say et al. (Chem. Eng. Prog., 80(10), 72-77 [1984]) to result in 50 percent more capacity than ordinary amine promoters of carbonate solutions. 

Isotope labeling by derivative formation with deuterated reagents is useful for the preparation of analogs such as dg-acetonides, da-acetates, da-methyl ethers, dg-methyl esters, etc. The required reagents are either commercially available or can be easily prepared. (The preparation of da-methyl iodide is described in section IX-F. Various procedures are reported in the literature for the preparation of dg-acetone, da-diazometh-ane57.i63.i73 and da-acetyl chloride. ) These reactions can be carried out under the usual conditions and they need no further discussion. A convenient procedure has been reported for the da-methylation of sterically hindered or hydrogen bonded phenolic hydroxyl functions by using da-methyl iodide and sodium hydroxide in dimethyl sulfoxide solution. This procedure should be equally applicable to the preparation of estradiol da-methyl ether derivatives. 

The present method utilizes dichlorocarbene generated by the phase-transfer method of Makosza4 and Starks.5 The submitters have routinely realized yields of pure distilled isocyanides in excess of 40%.6 With less sterically hindered primary amines a 1 1 ratio of amine to chloroform gives satisfactory results. Furthermore, by modifying the procedure, methyl and ethyl isocyanides may be prepared directly from the corresponding aqueous amine solutions and bromoform.7 These results are summarized in Table I. 

Mono- and bis(silyl)platinum(II) complexes are believed to play important catalytic roles in hydrosilylation, dehydrocoupling, and double silylation reactions with disilanes and hydrosilanes. A stable, mono(silyl)platinum(II) complex has been prepared by the oxidative addition reaction of the sterically hindered, primary arylsilane 2,6-Mes2C6H3SiH3 (Mes = 2,4,6-trimethylbenzene) to the platinum(O) species [Pt(PPr3)3] in hexane solution at room temperature.133 The colorless product m-[PLl 1(2,6-Mes2C6II3(11 )2Si)(PPr3)2] (21) was isolated as the OPPr3 adduct, and its... 

The first examples of mononuclear disulfur and diselenium complexes of platinum have been described.330 Reduction of the sterically hindered complex trans- PtC 2( P M e2A r)2] (Ar = 2,4, 6-tris[bis(trimethylsilyl)methyl]phenyl, 2,6-bis[bis(trimethylsilyl)-methyl]-4-[tris(trimethylsilyl) methyl]-phenyl) with lithium naphthalide in THF solution affords the platinum(0) species [Pt(PMe2Ar)2]. Oxidative addition of elemental sulfur or selenium yields the dichalcogenatoplatinum(II) complexes of the type [PtE2(PMe2Ar)2] (E = S, Se) containing a unique PtE2 ring system. The complexes are stable to air in the solid state, but slowly decompose in solution after several days at room temperature. 

Polymer formation is still observed with some sterically hindered thiolates, 2,4,6-Ao-propyl thiophenolate, and 2,4,6-trimethyl thiophenolate complexes have been studied. They can be synthesized by the reaction of Zn[N(SiMe3)2]2 with the appropriate arene chalcogenol. With the least steric bulk, the trimethyl derivative forms coordination polymers that can only be dissolved in strongly coordinating solvents. The iso-propyl derivative is more soluble forming oligomers in solution. 1... 

The bis-adducts are stable in the solid state at low temperatures. They dissociate in solution at ambient temperature. In the case of Me2Sb-SbMe2 a stable complex was formed only with the sterically hindered and less electrophilic t-Bu3Al. X-ray crystal structure analyses for [( -Bu)3M(R2Sb-SbR2)M( -Bu)3] (R = Me, Et M = Al, Ga) revealed that the distibine ligands adopt the anti conformation (Structural parameters of distibine complexes are summarized in Table I. 

Rapid bimolecular reactions are limited by diffusion of reactants in the liquid and solid phases. Diffusion occurs in polymers much more slowly than in liquids. Hence, such rapid reactions as recombination of free radicals occurs in polymers with rate constants of a few order of magnitude more slowly than in solution. For example, the reaction of sterically hindered phenoxyl with the peroxyl radical... 

Reactions described earlier were not limited by rotational diffusion of reactants. It is evident that such bimolecular reactions can occur that are limited not by translational diffusion but by the rate of reactant orientation before forming the TS. We discussed the reactions of sterically hindered phenoxyl recombination in viscous liquids (see Chapter 15). We studied the reaction of the type radical + molecule, which are not limited by translational diffusion in a solution but are limited by the rate of reactant orientation in the polymer matrix [28]. This is the reaction of stable nitroxyl radical addition to the double bond of methylenequinone. 

The first direct characterization of the structure of a sterically hindered diarylgermy-lene in solution was claimed for compound 26 (Ar = Ar5 in formula 11), using EXAFS (extended X-ray absorption fine structure), UVV (7-max 420 nm) and H and 13C NMR114. The UVV spectra of diarylgermylenes (26), their dimerization products (27) and the complexes formed with compounds containingp-electrons (28) were studied in solution115,116. 

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