Chiral Lewis base-catalyzed enantioselective

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

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]. 

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. 

Table 7.9 Enantioselective ring opening of meso-e poxides catalyzed by chiral Lewis bases [51a, 90-93].

Iseki et al. later improved the catalytic process and showed that chiral phos-phoramides 15,16, and 17, prepared from (S)-proHne, are suitable to catalyze the asymmetric allylation of aromatic aldehydes to give chiral homoallylic alcohols 34 with up to 88% ee (Scheme 13) [36,37]. The same group has also developed a chiral formamide 18 as a chiral Lewis base catalyst [38]. This catalyst is convenient for the allylation of aUphatic aldehydes with high enantioselectivity. A typical aromatic aldehyde, benzaldehyde, gives a low enantiomeric excess (Scheme 13). 

Denmark and Fan developed a chiral Lewis base (138)-catalyzed asymmetric a-addition of isocyanides to aldehydes with good to excellent enantioselectivity (Scheme 5.41) [84]. The protocol is applicable to non-chelating aldehydes, but it is a bimolecular transformation since the carboxylic acid is excluded from the 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]. 

A heterodinuclear rare earth metal SchifF base catalyzes enantioselective desymmetrization of cyclic and acyclic weyo-aziridines with malonates (Scheme 13). The combined use of two rare earth metal sources with different properties, Bronsted basic rare earth metal alkoxide and Lewis acidic rare earth metal triflate, was important to promote the desired ring-opening reactions. The La(0 Pr)3/Yb(OTf)3/SchifFbase complex gave chiral cyclic and acyclic y-amino esters in high yields and high enantiomeric excesses. 

It has been also found that chiral phosphine oxides (5)-BINAPO catalyzed silicon tetrachloride-mediated, enantioselective phosphonylation of aldehydes with trialkyl phosphites, led to formation of optically active a-hydroxyphosphonates with low to moderate enantioselectivities (ee 22-52%)7 This reaction constituted the first example of asymmetric Abra-mov-type phosphonylation of aldehydes with trialkyl phosphites catalyzed by chiral Lewis bases. 

Shao, P.-L., Chen, X.-Y, Ye, S. (2010). Formal [3+2] cycloaddition of ketenes and oxaziridines catalyzed by chiral Lewis bases enantioselective synthesis of oxazolin-4-ones. Angewandte Chemie International Edition, 49, 8412-8416. 

The Diels-Alder reaction of ester-tethered trienes is also known as a powerful methodology to construct polycylic Y lactones [68]. Romo et al. [69] surveyed effective organic nucleophilic catalysts for tandem intermolecular Diels-Alder reaction/lactonization reaction of achiral a, 3-unsaturated acid chlorides with dienyl alcohol 100 (Scheme 45). In this case, when chiral Lewis base 102 was used as a nucleophilic catalyst, excellent enantioselectivity was realized. Lipase-catalyzed domino kinetic resolution/intramolecular Diels-Alder reaction of furfuryl alcohols with acrylic acids was also carried out by Akai and Kita [70]. 

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. 

This class of chiral Lewis base catalysts was also applicable to the enantioselective aldol reactions of trichlorosilyl enol ethers (Scheme 7.14) [24, 25). As included in Scheme 7.14, Denmark devised chiral bipyridine N.N -dioxide 8 and demonstrated that it smoothly catalyzed the aldol addition of methyl acetate-derived trichlorosilyl ketene acetal to a series of ketones with good to high enantioselectivi-ties [25],... 

With the current emphasis on enantioselective synthesis, it is not surprising that numerous, highly successful asymmetric versions of aldol reaction have been developed. Noncatalytic methods involve the use of stoichiometric amounts of a chiral auxiliary in diastereoselective aldol reactions. Small-molecule-catalyzed aldol reactions typically would involve the use of a chiral Lewis acid for aldehyde activation or a chiral Lewis base for donor... 

This procedure describes the preparation and application of an effective chiral catalyst for the enantioselective Diels-Alder reaction.11 The catalyst is derived from optically active 1,2-diphenylethylenediamine, the preparation of which (either antipode) was described in the preceding procedure. The aluminum-based Lewis acid also catalyzes the cycloaddition of crotonoyl oxazolidinones with cyclopentadiene,11 and acryloyl derivatives with benzyloxymethylene-cyclopentadiene. The latter reaction leads to optically pure intermediates for synthesis of prostaglandins.11... 

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. 

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