Enantioselective Lewis base-catalyzed

Such phosphazenes could play a role in enantioselective Lewis base-catalyzed transformations (13JA15306, 14CC4319). The catalytic performances of the phosphazene hase 129-HI have been evaluated in the electrophilic amination of2-alkyltetralones 130 with azodicarboxylate. The best conditions employed the use of 10mol% of phosphazene 129-HI and 20 mol% of NaHMDS. The reaction afforded excellent yields and ee, up to 99% and 97%, respectively. However, the position of methoxy groups on the tetralones 130 has a deep influence on enantioselectivity and yield. The 6- and 8-methoxy substituted tetralones 130 require higher temperatures for sufficient conversion 8-MeO-130 gave only 78% conversion and 10% ee at 25 °C (Scheme 34). 

These highly enantioselective Lewis-acid/Lewis-base-catalyzed dialkylzinc and phenylzinc addition reactions to imines give rise to arylalkylamides and diaryl-methylamides in excellent yields and enantioselectivities. Due to the simplicity of the process and the good availability of the imine precursors 23 from the corresponding aldehydes, wide applicability of the reported catalytic reaction can be expected. 

In a related study Denmark and Fan [22] investigated chiral Lewis base-catalyzed enantioselective a-additions of isocyanides to aldehydes in a Passerini-type reaction (Scheme 9.14). The development of the reaction was based on the concept of Lewis base activation of a weak Lewis acid such as SiCl4 forming a trichlorosilyl-Lewis base adduct which is capable of activating aldehydes towards nucleophilic attack. 

Scheme 9.14. Lewis base-catalyzed enantioselective Passerini-type reactions.

Many noticeable examples of chiral Lewis base catalyzed allylation of carbonyl compounds have also appeared. Iseki and coworkers published a full paper on enantioselective addition of allyl- and crotyltrichlorosilanes to aliphatic aldehydes catalyzed by a chiral formamide 28 in the presence of HMPA as an additive [41]. This method was further applied to asymmetric allenylation of aliphatic aldehydes with propargyltrichlorosilane [40]. Nakajima and Hashi-moto have demonstrated the effectiveness of (S)-3,3 -dimethyl-2,2 -biquinoline N,AT-dioxide (29) as a chiral Lewis base catalyst for the allylation of aldehydes [42]. In the reaction of (fs)-enriched crotyltrichlorosilane (54 , E Z=97 3) with benzaldehyde (48), y-allylated anfi-homoallylic alcohol 55 was obtained exclusively with high ee while the corresponding syn-adduct was formed from its Z isomer 54Z (fs Z= 1 99) (Scheme 6). Catalytic amounts of chiral urea 30 also promote the asymmetric reaction in the presence of a silver(I) salt, although the enantioselectivity is low [43]. 

Denmark, S. E., Fan, Y. The First Catalytic, Asymmetric a-Additions of Isocyanides. Lewis-Base-Catalyzed, Enantioselective Passerini-Type Reactions. J. Am. Chem. Soc. 2003, 125, 7825-7827. 

Scheme 5.41 Lewis base-catalyzed enantioselective truncated Passerini reaction.

There is a frequently noted incompatibility of organoiithiums with many chiral Lewis acids, which are often employed for asymmetric openings of epoxides [99]. Analogous Lewis base-catalyzed reactions are rare [100]. However, activation by Lewis acids, such as BFj OEt2, is necessary for the opening of less reactive epoxides [101]. While organoiithiums are rarely employed, applications of hetero-nucleophiles are well known in enantioselective desymmetrizations of meso-epoxides [102]. 

Denmark SE, Ean Y (2005) Catalytic, enantioselective a-additions of isocyanides Lewis base catalyzed Passerini-type reactions. J Org Chem 70 9667-9676... 

Demnark SE, Fan Y, Eastgate MD (2005) Lewis base catalyzed, enantioselective aldol addition of methyl trichlOTOsUyl ketene acetal to ketraies. J Org Chem 70 5235—5248... 

Denmark SE, Fan Y (2003) The first catalytic, asymmetric alpha-additions of isocyanides. Lewis-base-catalyzed, enantioselective Passerini-type reactions. J Am Chem Soc 125 7825-7827... 

Denmark SE, Wilson TW, Burk MT, Heemstra JR (2(X)7) Enantioselective construction of quaternary stereogenic caarbons by the lewis base catalyzed additions of silyl ketene imines to aldehydes. J Am Chem Soc 127 14864-14865... 

The enantioselective synthesis of axially chiral P—N ligands was also accomplished by rhodium-catalyzed [2 + 2+-2] cycloaddition. The reactions of 1,6-diynes 75 with diphenylphosphinoyl-substituted isoquinolinyl acetylenes 76 furnished diphenylphosphinoyl-substituted axially chiral 1-arylisoquinolines 77 with high yields and ee values (Scheme 9.28) [23], The new diphenylphosphinoyl-substituted axially chiral 1-arylisoquinoline 77 (Z = NTs, R = Me) was derivatized to the corresponding axially chiral P—N ligand 78 and isoquinoline A-oxide 79 without racemization, which could be used in the rhodium-catalyzed hydroboration and Lewis base-catalyzed allylation, respectively [23],... 

The Lewis base-catalyzed reactions oftrichlorosilyl-protected carbon nucleophiles are important as silicon Lewis acid-promoted reactions. This review, however, does not deal with these topics because of the limited space and the availabihty of recent reviews [2, 38-40]. Denmark and coworkers have recently succeeded in enantioselective reactions using SiCU and chiral Lewis base catalysts, which are detailed in this section. 

Scheme 3-113. Chiral Lewis-base catalyzed enantioselective allylation of aldehydes using allylsilanes.

A majority of the reported enantioselective Lewis acid-catalyzed allylation processes employ complexes with chiral ligands based on the 1,1-binaphthyl skeleton. In 1993, Umani-Ronchi and Tagliavini [122] and Keck [123] independently reported enantioselective allylation of aldehydes with BINOL-Ti(IV) catalysts 195 (from BINOL/TiCl2(Oi-Pr)2) and 196 (from BINOL/ Ti(Oi-Pr)4), respectively (Equation 13). Excellent enantioselectivity was observed with both catalyst systems ( 90% ee). 

For the activation of a substrate such as 19a via coordination of the two carbonyl oxygen atoms to the metal, one should expect that a hard Lewis acid would be more suitable, since the carbonyl oxygens are hard Lewis bases. Nevertheless, Fu-rukawa et al. succeeded in applying the relative soft metal palladium as catalyst for the 1,3-dipolar cycloaddition reaction between 1 and 19a (Scheme 6.36) [79, 80]. They applied the dicationic Pd-BINAP 54 as the catalyst, and whereas this type of catalytic reactions is often carried out at rt or at 0°C, the reactions catalyzed by 54 required heating at 40 °C in order to proceed. In most cases mixtures of endo-21 and exo-21 were obtained, however, high enantioselectivity of up to 93% were obtained for reactions of some derivatives of 1. 

We employed malononitrile and l-crotonoyl-3,5-dimethylpyrazole as donor and acceptor molecules, respectively. We have found that this reaction at room temperature in chloroform can be effectively catalyzed by the J ,J -DBFOX/Ph-nick-el(II) and -zinc(II) complexes in the absence of Lewis bases leading to l-(4,4-dicya-no-3-methylbutanoyl)-3,5-dimethylpyrazole in a good chemical yield and enantio-selectivity (Scheme 7.47). However, copper(II), iron(II), and titanium complexes were not effective at all, either the catalytic activity or the enantioselectivity being not sufficient. With the J ,J -DBFOX/Ph-nickel(II) aqua complex in hand as the most reactive catalyst, we then investigated the double activation method by using this catalyst. 

Reymond, S. Brunei, J. M. Buono, G. (2000) New development in the enantioselective ring opening of meso-epoxides by various ion silicon sources catalyzed by an o-methoxyaryldiazaphosphonamide Lewis base., Tetrahedron Asymmetry, 11 4441-4445. 

Cyanation of aldehydes and ketones is an important chemical process for C C bond formation." " Trimethylsilyl cyanide and/or HCN are commonly used as cyanide sources. The intrinsic toxicity and instability of these reagents are problematic in their applications. Acetyl cyanide and cyanoformates were used as cyanide sources in the enantioselective cyanation of aldehydes catalyzed by a chiral Ti complex and Lewis base (Scheme 5.31)." The Lewis base was necessary for the good yields and selectivities of these reactions. The desired products were obtained in the presence of 10mol% triethyl amine and 5mol% chiral titanium catalyst (Figure 5.14). Various aliphatic and aromatic aldehydes could be used in these reactions. 

Chiral base catalysis was classified into five sections and reviewed. Although the reactions described herein are promoted by Bronsted or Lewis bases, the Lewis acidic characteristics of metals play important roles in both substrate activation and enantioselection. Compared with chiral Lewis acid-catalyzed reactions,... 

Denmark utilized chiral base promoted hypervalent silicon Lewis acids for several highly enantioselective carbon-carbon bond forming reactions [92-98]. In these reactions, a stoichiometric quantity of silicon tetrachloride as achiral weak Lewis acid component and only catalytic amount of chiral Lewis base were used. The chiral Lewis acid species desired for the transformations was generated in situ. The phosphoramide 35 catalyzed the cross aldolization of aromatic aldehydes as well as aliphatic aldehydes with a silyl ketene acetal (Scheme 26) [93] with good yield and high enantioselectivity and diastereoselectivity. 

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