Catalytic Asymmetric Synthesis. Группа авторов

Figure 2.4. Function of chiral phosphoric acid.

      2.2.2. Mode of Activation of Chiral Phosphoric Acids and Related Compounds

CPA is, in principle, a Brønsted acid, but the phosphoryl oxygen plays a crucial role as a basic site (Figure 2.4). The bifunctional nature of CPA and other chiral Brønsted acids is, in many cases, critical for the high enantioselectivity and reactivity. CPA is considered to be “proton‐bearing chiral counteranion.” List expanded the concept of chiral Brønsted acid to “asymmetric counteranion‐directed catalysis” (ACDC) [23]. Toste also proposed “chiral anion catalysis” [24]. The concept will be discussed in detail in Chapter 4 [25]. Metal phosphates are also employed as Lewis acid catalysts [26]. Cooperative and/or relay catalyst system of combining chiral Brønsted acids with metal‐based catalysts or photoredox catalysts have also attracted much attention lately [27].

      2.2.3. Effect of Metal Salts

      In addition to CPA per se, metal phosphates function as achiral Lewis acid, and numerous kinds of enantioselective reactions were reported. Examples include Yb triphosphates by Inanaga et al. [28], lithium phosphates by Ishihara et al. [29], calcium phosphates by Masson and Zhu [30], and magnesium phosphates by Antilla [31].

Ishihara conducted a reinvestigation of the report of Terada [9] and pointed out the possible formation and contamination of BINOL‐derived phosphoric acid during purification on silica gel (Figure 2.5). They cautioned that such impurities may have a substantial influence on the catalytic activity [32]. Subsequently, Klussmann and List analyzed the impurities of CPA 6e bearing 2,4,6‐(i‐Pr)₃C₆H₂ groups at 3,3′‐positions of BINOL (TRIP) by inductively coupled plasma optical emission spectrometry (ICP‐OES) and found that TRIP contained various alkali and alkaline earth metals as major impurities. Because metal phosphates are generated during the preparation of CPA and/or the purification by silica gel chromatography, washing with hydrochloric acid is strongly recommended to obtain free phosphoric acid [33].

Figure 2.5. Metal salts of chiral phosphoric acid.

2.3. NUCLEOPHILIC REACTIONS

      2.3.1. Reactions with Imines and Iminium Salts

BINOL‐derived CPA 6a is available in bulk amounts and is employed as a resolving reagent for amines [34]. In 2004, Akiyama reported a Mannich‐type reaction between aldimines bearing the 2‐hydroxyphenyl moiety on nitrogen and ketene silyl acetals catalyzed by CPA 6c, derived from (R)‐BINOL bearing 4‐nitrophenyl groups at 3,3′‐positions, which gave β‐amino‐α‐alkyl or α‐siloxy amino esters in preference of the syn isomer with 81–96% ee (Scheme 2.1a) [8]. The use of aldimines derived from 2‐hydroxyaniline is critical for the excellent enantioselectivity. Based on the theoretical study by Yamanaka, the Mannich‐type reaction is proposed to proceed through the protonation of imine with CPA followed by the nucleophilic attack via zwitterionic and nine‐membered cyclic transition state (TS‐1) [35]. Concurrently, Terada reported a direct Mannich reaction between N‐Boc aldimines and pentan‐2,4‐dione catalyzed by CPA 6j to give the adducts with 90–98% ee (Scheme 2.1b) [9].

Scheme 2.1. Mannich reaction by Akiyama (a)

      (Source: Based on [8])

      , and by Terada (b)

      (Source: Based on [9]).

Yamamoto reinvestigated the Mannich‐type reaction[8] and found that CPA 6k, bearing 2,4,6‐Me₃‐3,5‐(NO₂)₂C₆ moiety, was more effective for the Mannich‐type reaction, furnishing β‐amino esters with higher enantioselectivity in comparison with CPA 6b (Scheme 2.2a) [36]. The higher enantioselectivity (up to >99% ee) was ascribed to both steric and electronic effects from the three methyl groups. Furthermore, when phosphoramide 2a bearing 3,5‐(NO₂)‐4‐CH₃C₆H₂ groups was used, N‐phenyl aldimines were also found to be suitable substrates and use of N‐2‐hydroxyphenyl‐substituted aldimine was obviated without compromising the enantioselectivity (Scheme 2.2b).