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Phosphazenes are pentavalent phosphorus compounds possessing a P=N double bond and three P–N single bonds, and are recognized as the strongest uncharged organobases. The basicity of the simplest P1‐phosphazenes, which possess secondary amine subunits on the iminophosphorane core, is even higher than that of guanidines. Although this class of compounds was first introduced by Schwesinger and Schlemper in 1987 [93], the chiral variants were not prepared and utilized as chiral organobase catalysts until 2007. Ooi and co‐workers utilized phosphazenes as a platform for chiral organobase catalysts for the first time [94]. They designed and synthesized chiral P1‐phospazene catalysts (M)‐33 and (P)‐34 containing a pseudo‐C ₂‐symmetric 5,5‐membered spirocyclic core structure (Figure 3.13).

Figure 3.13. Chiral P1‐phosphazene catalysts.

The characteristic feature of the structural motif is that the direction of not only substituents on the rigid spirocycles but also N‐H protons in the conjugate acid forms can be accurately regulated. In addition, hydrogen bond donor and acceptor sites are arranged side by side around the central phosphorus atom: the nitrogen atom of the iminophosphorane moiety (P=N) functions as a hydrogen bond acceptor, while the N‐H moiety attached to the iminophosphorane core functions as a hydrogen bond donor. The high catalytic activity of this class of chiral organobases was demonstrated in a series of the direct Henry reaction [95] and the hydrophosphonylation of aldehydes (Scheme 3.49) [96].

Scheme 3.49. Enantioselective addition of nitroalkanes and dialkyl phosphites to aldehydes catalyzed by (M)‐33. (a) Source: Based on [95]. (b) Source: Based on [96].

The computational study by Simón and Paton suggested the mechanism involving a single catalyst molecule that makes hydrogen bonds with both a nucleophile and an electrophile, transferring a proton to the electrophile preventing the negative charge accumulation (Figure 3.14) [97].

Figure 3.14. Proposed transition‐state model.

The chiral P1‐phosphazene catalysts (P)‐34 exhibited the distinctive feature in the Michael addition reactions involving the multiple selectivity control (Scheme 3.50). For instance, catalyst (P)‐34a promoted the enantioselective addition of 2‐benzyloxythiazol‐5(4H)‐ones to β‐substituted alkynyl N‐acylpyrazoles with high E selectivity (Scheme 3.50a) [98]. The addition of azlactones to δ‐substituted dienyl N‐acylpyrroles and ζ‐substituted trienyl N‐acylpyrroles proceeded in highly 1,6‐ and 1,8‐selective fashion, respectively, under the catalysis of (P)‐34b, and the corresponding adducts were obtained in high yields with high diastereo‐ and enantioselectivities (Scheme 3.50b) [99]. Furthermore, (P)‐34c efficiently catalyzed the 1,6‐addition of azlactones to enynyl N‐acylpyrazole and the consecutive γ‐protonation of the vinylogous enolate to afford Z,E‐configurated conjugated dienes, while the application of a bifunctional chiral tertiary amine catalyst provided the 1,4‐addition products (Scheme 3.50c) [100].

Scheme 3.50. Enantioselective Michael addition reactions catalyzed by (P)‐34. (a)

Source: Based on [98].

(b)

Source: [99].

(c)

Source: Based on [100].

Furthermore, this class of chiral catalysts was successfully utilized in the development of new types of catalytic enantioselective reactions. For instance, Ooi, Johnson, and co‐workers developed the enantioselective aldol‐type reaction of α‐hydroxy phosphonoacetates (Scheme 3.51) [101]. This reaction involves a catalytic generation of the reactive glycolate enolate 36 from an α‐hydroxy phosphonoacetate 35 through the [1,2]‐phospha‐Brook rearrangement and the subsequent enantioselective addition to an aldehyde. The group also reported the related enantioselective three‐component coupling reaction of isatin derivatives, aldehydes, and dialkyl phosphites [102].

Scheme 3.51. Enantioselective aldol‐type reaction of α‐hydroxy phosphonoacetates catalyzed by (P)‐34d.

Source: Based on [101].

As the other remarkable catalytic enantioselective reaction, Ooi and co‐workers developed the enantioselective Payne‐type oxidation of N‐sulfonyl imines based on the combined use of H₂O₂ and trichloroacetonitrile under the catalysis of (P)‐34e (Scheme 3.52) [103]. In this reaction system, the reactive organic peroxy acid 37, which was catalytically generated in situ, was successfully controlled by the chiral catalyst molecule.

Scheme 3.52. Enantioselective Payne‐type oxidation of N‐sulfonyl imines catalyzed by (P)‐34e.

Source: [103].