The ability to modulate the nucleophilicity and Lewis basicity of N-heterocyclic carbenes is pivotal to their application as organocatalysts. Herein we examine the impact of the N-substituent on the nucleophilicity and Lewis basicity. Four N-substituents popular in NHC organocatalysis, namely, the N-2,6-(CH3O)2C6H3, N-Mes, N-4-CH3OC6H4, and N-tert-butyl groups, have been examined and found to strongly affect the nucleophilicity. Thus, the N-2,6-(CH3O)2C6H3 group provides the most nucleophilic imidazolylidene NHC reported and the N-tert-butyl group one of the least. This difference in nucleophilicity is reflected in the catalyst efficiency, as observed with a recently reported trienyl ester rearrangement.
The
Brønsted basicities pK
aH (i.e.,
pK
a of the conjugate acids) of 32 pyrrolidines
and imidazolidinones, commonly used in organocatalytic reactions,
have been determined photometrically in acetonitrile solution using CH acids as indicators. Most investigated
pyrrolidines have basicities in the range 16 < pK
aH < 20, while imidazolidinones are significantly less
basic (10 < pK
aH < 12). 2-(Trifluoromethyl)pyrrolidine
(A14, pK
aH 12.6) and the
2-imidazoliummethyl-substituted pyrrolidine A21 (pK
aH 11.1) are outside the typical range for pyrrolidines
with basicities comparable to those of imidazolidinones. Kinetics
of the reactions of these 32 organocatalysts with benzhydrylium ions
(Ar2CH+) and structurally related quinone methides,
common reference electrophiles for quantifying nucleophilic reactivities,
have been measured photometrically. Most reactions followed second-order
kinetics, first order in amine and first order in electrophile. More
complex kinetics were observed for the reactions of imidazolidinones
and several pyrrolidines carrying bulky 2-substituents, due to reversibility
of the initial attack of the amines at the electrophiles followed
by rate-determining deprotonation of the intermediate ammonium ions.
In the presence of 2,4,6-collidine or 2,6-di-tert-butyl-4-methyl-pyridine, the deprotonation of the initial adducts
became faster, which allowed the rate of the attack of the amines
at the electrophiles to be determined. The resulting second-order
rate constants k
2 followed the correlation
log k
2(20 °C) = s
N(N + E), where electrophiles
are characterized by one parameter (E) and nucleophiles
are characterized by the two solvent-dependent parameters N and s
N. In this way, the organocatalysts A1–A32 were integrated in our comprehensive
nucleophilicity scale, which compares n-, π-, and σ-nucleophiles.
The nucleophilic reactivities of the title compounds correlate only
poorly with their Brønsted basicities.
A series of α,β‐unsaturated iminium ions derived from substituted cinnamaldehydes and C2‐ and C5‐substituted chiral imidazolidin‐4‐ones were isolated and characterized in solution and in the solid state. The kinetics of the reactions of the iminium ions with silyl ketene acetals were determined in dichloromethane at 20 °C. The resulting second‐order rate constants were used to estimate the electrophilicity E of the iminium ions according to the linear free energy relationship log k2(20 °C)=sN(N+E). The kinetics for the reactions of two of the iminium ions with tributylphosphine were studied by laser flash spectroscopy and their second‐order rate constants were found to agree within a factor of 2.2 with those calculated by using the linear free energy relationship above.
A new synthesis route for phosphates in an organic solvent at low temperatures is presented. The synthesis was done by dispersing a nitrate salt and phosphorus pentoxide in dimethyl sulfoxide. The synthesis can be performed under water-free conditions and yielded several organic and inorganic phosphates. Crystal structure solution of bistetramethylammonium hydrogencyclotriphosphate, [N(CH3)4]2HP3O9, was achieved by combining information gained from powder X-ray diffraction, liquid NMR and solid state (2D) NMR. The molecular structure of rubidium cyclotetraphosphate, Rb4P4O12, was determined using liquid state NMR and solid state (2D) NMR spectroscopy.
X-ray structures of enamines and iminium ions derived from 2-tritylpyrrolidine (Maruoka catalyst) and 2-(triphenylsilyl)pyrrolidine (Bolm-Christmann-Strohmann catalyst) have been determined. Kinetic investigations showed that enamines derived from phenylacetaldehyde and pyrrolidine (R = H) or 2-(triphenylsilyl)pyrrolidine (R = SiPh3) have similar reactivities toward benzhydryl cations Ar2CH(+) (reference electrophiles), while the corresponding enamine derived from 2-tritylpyrrolidine (R = CPh3) is 26 times less reactive. The rationalization of this phenomenon by negative hyperconjugative interaction of the trityl group with the lone pair of the enamine nitrogen is supported by the finding that the trityl group in the 2-position of the pyrrolidine increases the electrophilic reactivity of iminium ions derived from cinnamaldehyde by a factor of 14. The consequences of these observations for the rationalization of the reactivity of the Jørgensen-Hayashi catalyst (diphenylprolinol trimethylsilyl ether) are discussed.
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