Application of Divalent N(I) Complexes as a Phase-Transfer Catalyst (PTC)

reactant from one phase to another phase. Generally ionic reactants are soluble in an aqueous phase and insoluble in organic phase. In heterogenous two- phase system, phase transfer catalysts cause or accelerate the reaction between the ionic reactants, and the substrate soluble in the organic phase. The catalyst possesses a lipophilic cation which allows it to reside in the organic phase. The reagent, as an anionic species in the form of lipophilic counterion, introduces itself into the organic phase continuously. Phase-transfer catalysis is attractive for industrial applications due to the low cost, operational simplicity, and

51 commercial availability. To have a sustainable catalyst, the lipophilic cation portion of the catalyst should be stable in the basic/nucleophilic reaction conditions. However, most organic cations suffer from a lack of stability in concentrated aqueous alkali hydroxide solutions, or in the presence of strong nucleophiles, especially at high temperature. As such, there is growing interest in the development of stable organic cations in the field of Phase- transfer catalysis.69

In 1991, Schwesinger et al.70 reported a stable and easily accessible phosphazenium fluoride 118•F– as a source of naked fluoride ions in THF solutions (Scheme 29). The synthesis started with the reaction of PCl5 with NH4Cl to give salt 116. Subsequent addition

of dimethylamine and NaBF4 afforded 118•BF4–. Also, hexamethylphosphoric triamide

(HMPA) and salt of 117 were formed as a by-product. It was found that peralkylated cation 118 showed much higher stability towards nucleophiles than conventional organic cations.

Scheme 29. Synthesis of phosphazenium fluoride salt 118•F–.

The commercially available tetrakis{[tris(dimethylamino)phosphoranyliden] amino}phosphonium fluoride (P5-phosphazenium cation, Figure 20) has been used for the

52 the P5 cation requires a high molecular weight for delocalization of the positive charge

through the network containing P and N atoms. Drawing upon the known similarity of N- heterocyclic carbenes (NHC) and phosphines, both considered to be strong -donors yet poor back-bonding -acceptors, Lyapkalo et al.71 in 2009, prepared a series of bis(N,N’- dialkylimidazolium)amides (BIMA) 123a-c from tetraalkylimidazolin-2-ylidene precursors 120a-c. These were derived from 1,3-dialkyl-4,5-dimethyl-1H-imidazole-2(3H)-thiones 119a-c. Conversion of 120a-c to 121a-c using C2Cl6 and 120a-c to 122a-c employing

Me3CN3, NH4BF4 was carried out. KF-mediated coupling of the two salts of 121a-c and

corresponding derivatives 122a-c afforded BIMA salts 123a-c (Scheme 30). Interestingly, there was no explicit mention in the aforementioned report that the prepared phase-transfer catalyst was conformed to be a divalent N(I) complexes (e.g., N(I)(←:L)2) (L = NHC; N,N’-

dialkyl-4,5-dimethylimidazol-2-ylidenes).

Figure 20. Structure of tetrakis{[tris(dimethylamino)phosphoranyliden] amino}phosphonium fluoride.

53 The hydrolytic cleavage of 123a gave the imidazolinone derivatives 124 and 125 (Scheme 31). In the rate-limiting step, OHˉ attacked the carbon center of 123a, which in turn dearomatized the imidazolium ring. As such, an enhancement in the activation barrier resulted in an increased base resistance. Table 2 shows the half-lives of the organic cations

Scheme 31. Hydrolytic cleavage of the BIMA cation.

123a-c while vigorously stirred and refluxed, in a biphasic mixture of PhCl/50% aqueous KOH. The neopentyl-substituted cation 123b displayed the most stability in the BIMA series. The stability of BIMA cations can be explained by the distribution of the positive charge throughout aromatic imidazolium moiety.71

Table 2. Half-lives of the organic cation 123a. Condition: vigorously stirred biphasic mixture of PhCl/50% aqueous KOH, reflux (115 °C inner temperature, 145 °C oil-bath temperature).

Entry Compound Reaction time [h] Conversion [%] t½ [h]

1 123a.BF4 24 42 31

2 123b.BF4 48 trace Stable

3 123c.BF4 21 33 36

Furthermore, additional steric protection is produced by the presence of bulky N-alkyl groups, as well as a decrease in Hofmann degradation due to the low charge density on the endocyclic nitrogen atoms. This was especially true in the case of the tetraneopentyl cation

54 123b. The synthesized imidazolium cations 123a-c were stable in basic conditions at elevated temperature. The stability of the compound 123a-c can be attributed to the distribution of positive charge through the aromatic imidazolium moiety. In addition, bulky N-alkyl groups on the nitrogen of imidazolium moiety provide higher stability due to steric hinderance. Overall, the possibility of Hofmann degredation was strongly diminished due to the aforementioned stability of the synthesized imidazolium cations. The stability of these cations paved the way for their application as a phase-transfer catalyst under harsh reaction conditions.71

Building upon Lyapkalo et al., Tan and co-workers72 worked with bicyclic guanidines, containing five nitrogen atoms in conjugation, as chiral Brønsted base catalysts for enantioselective reactions. They rationalized that the basicity of conjugated penta- nitrogen systems can be greater than guanidine. As such, they recently reported a number of structurally related C2-symmetric chiral catalysts 129 that were christened Pentanidium

(Scheme 32). It was found that Pentanidium was as an excellent phase-transfer catalyst and had successful application in catalytic enantioselective Michael addition reactions. The synthesis of pentanidium chloride 129a started from commercially available (S,S)- diphenyldiamineoethane 126, which, with simple manipulations, gives imidazoline salt 127. Subsequent conversion of salt 127 to imine 128 and condensation of 127 and 128 afforded pentanidium chloride 129 (Scheme 32). Using the catalyst 129a-e as a chiral phase-transfer

55 Scheme 32. Preparation of Pentanidium chloride 129.

catalyst for Michael addition reactions of tert-butyl glycinate-benzophenone Schiff base 130 with various α,β-unsaturated acceptors 131a-f, afforded products 132a- f, with ee of up to 97% (Scheme 33). In addition, the same conditions were used for reactions of Schiff base

Scheme 33. Michael addition of tert-butyl glycinate-benzophenone Schiff base to various a,b-unsaturated acceptors.

133 with chalcones 134a-f which led to adducts135a-f as a single diastereomer and ee up to 94% (Scheme 34). The developed chiral pentanidium exhibited potential applications as a phase-transfer catalyst and employing the catalyst in Michael addition reaction led to high diastereo- and enantioselectivity.72

56 Scheme 34. Michael addition of tert-butyl glycinate-benzophenone Schiff base to various

chalcones acceptors.

1.3. Fluorination