The basicity of N‐alkyl triaryliminophosphorane was determined to be comparable to that of guanidines. The attractive feature of the catalyst design is high modularity. The catalysts incorporating a variable hydrogen bond donor, chiral amino acid‐derived scaffold, and triaryliminophosphorane are readily synthesized via a last step Staudinger reaction of a chiral organoazide and a triarylphosphine. The synthetic potential of this class of catalysts was first demonstrated in the enantioselective addition of nitromethane to ketimines catalyzed by 32a in 2013 (Scheme 3.47) [87].
Scheme 3.47. Enantioselective addition of nitromethane to ketimines catalyzed by 32a.
Source: Based on [87].
After that, the BIMP catalysts 32 were successfully utilized in several enantioselective reactions (Scheme 3.48). For instance, a series of enantioselective sulfa‐Michael additions including that with α‐substituted acrylates was developed (Scheme 3.48a) [88]. On the other hand, the enantioselective synthesis of conjugated cyclohexanones through a facial selective 1,3‐proton shift was achieved by using 32c (Scheme 3.48b) [89]. The related enantioselective 1,3‐proton shift was also utilized in the total synthesis of a natural product, (‐)‐himalensine A [91]. Furthermore, 32d having a sterically demanding amide moiety efficiently promoted the direct aldol addition of less acidic acetophenone derivatives to α‐fluorinated ketones to provide the corresponding adducts in high yields with high enantioselectivities (Scheme 3.48c) [90]. Johnson and co‐workers utilized the BIMP catalysts in their development of enantioselective reactions, such as the enantioselective additions of nitroalkanes and alkyl thiols to enone diesters, and the enantioselective three‐component coupling reaction of benzylidene pyruvates, aldehydes, and dialkyl phosphites [92].
Scheme 3.48. Enantioselective reactions catalyzed by 32. (a)
Source: [88].
(b)
Source: Based on [89].
(c)
Source: Based on [90].
3.4.3. Chiral P1‐Phosphazene Catalysts
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.