Chiral phosphoric add catalyst

Recently, a new approach was pursued combining organocatalysis with heterogeneous catalysis [11]. In this case, molecular hydrogen is used as hydrogen source and supported noble metal catalysts for the activation of hydrogen. The implementation of chirahty is affected by a suitable modifier such as chiral phosphoric add esters (P-add) ]55]. 

N-Boc-protected ethyl trifluoropyruvate imine was effectively used in a F-C reaction with indole derivatives for synthesizing, in high selectivities, quaternary a-amino acids via catalysis with chiral phosphoric acid 26e [64]. A binaphthyl-based chiral sulfonimide [42c] and a chiral squaramide-based hydrogen bond donor [42a] were used as effective catalysts for promoting F-C reaction of indoles with imines. Recently, the F-C alkylation of arenes with glyoxylate imine was described via a chiral phosphoric add (Scheme 35.11) [34]. 

List has developed the concept of asymmetric counter-ion directed catalysis and applied it in organocatalytic transformations. One of the first pioneering studies in the synergic use of organocatalyst and transition metal was the combination of a Pd(0) catalyst with a chiral phosphoric add in a highly enantioselective Tsuji-Trost type a-allylation of branched aldehydes (Scheme 26.12) [81]. 

Chiral phosphoric add analogs as catalysts in the F-C alkylation reaction of indoles with a,P-unsaturated aromatic enones were also devised [53]. p,y-Unsaturated a-ketoesters were also used as electrophiles in organocatalyzed F-C alkylations of indoles and 2-naphthols. With indoles, chiral addic N-triflylphos-phoramide was successfully employed (Scheme 35.4) [28], whereas in the presence of 2-naphthols a thiourea-based catalyst showed better capadty to mediate a sequential F-C/cycUzation process, giving naphthopyran scaffolds in moderate yields and selectivities (up to 90% ee) [54]. Recently, a,(i-unsaturated acyl phos-phonates were effectively used as hydrogen bond acceptors for F-C alkylations of indole derivatives in the presence of thiourea catalyst ent-19 [55]. 

In 2007, AntiUa and coworkers described the Brpnsted add-catalyzed desymmetrization of me yo-aziridines giving vicinal diamines [75]. hi recent years, chiral phosphoric acids have been widely recognized as powerful catalysts for the activation of imines. However, prior to this work, electrophiles other than imines or related substrates like enecarbamates or enamides have been omitted. In the presence of VAPOL-derived phosphoric acid catalyst (5)-16 (10 mol%) and azidotrimethylsilane as the nucleophile, aziridines 129 were converted into the corresponding ring-opened prodncts 130 in good yields and enantioselectivities (49-97%, 70-95% ee) (Scheme 53). 

A broad range of enantiomericaUy pure 4,5-dihydrobenzo[r [l,3]diox-epines 177 have been prepared via a four-component Mannich reaction and subsequent intramolecular oxo-Michael reaction (14CC2196). The reactions proceeded with both high enantio- and diasteroselectivity, utilizing a dual catalytic system of Rh2(OAc)4 and a chiral phosphoric acid 178. The rhodium catalyst forms the protic oxonium ylide 174 from a diazo compound 171 and this subsequently adds to imine 175, formed in situ. The resulting enantiomericaUy enriched intermediate 176 then undergoes an intramolecular and diastereoselective oxo-Michael addition to form the final product 177. 

In 2006, Gong and coworkers reported the first chiral Bronsted add-catalyzed asymmetric direct aza-hetero-Diels-Alder reaction [70]. Phosphoric acid catalyst 160 exhibited excellent catalytic activity and selectivity for the reaction of cyclohex-enone (31) with a broad range of aldimines 159 to produce N-containing heterocycles 162 with up to 87% ee (Scheme 38.47). More recently, Carter and coworker developed the modified proline catalyst 161 for this reaction, and high levels of enantioselectivity and diastereoselectivity were obtained (Scheme 38.47) [71]. Interestingly, the aromatic imines favor exo products while the aliphatic imines favor endo products. 

An asymmetric synthesis of conformationally restricted amino acid precursors (368) involving alkynols (366) and azalactones (367), was catalysed by a combined catalyst system consisting of a chiral phosphine (369) and a phosphoric add (253) (Scheme 97). ... 

Also, Gong and co-workers reported a Brpnsted add catalyzed three-component asymmetric 1,3-dipolar cycloaddition reactions between aldehydes 213, amino esters 214, and dipolarphiles 215 by catalyst 216, providing pyrrolidines 217 in high yields with excellent enantioselectivity. Scheme 3.69 [86], The methodology introduced a concept that stereochemistry can be controlled by use of a chiral Br0nsted acid (BH), e.g., phosphoric acid. The chiral BH provided sufficient acidity... 

Br0nsted Acid Organocatalysis. The field of Brpnsted add organo-catalysis [151] is clearly dominated by chiral binol-derived phosphoric acids, which after the seminal reports of Akiyama et al. [152] and of Uraguchi and Terada [153] have become one of the most powerful types of organic catalysts [154]. Figure 2.33... 

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