Asymmetric quaternary ammonium fluorides

The enantioselective addition of a nucleophile to a carbonyl group is one of the most versatile methods for C C bond formation, and this reaction is discussed in Chapter 2. Trifluoromethylation of aldehyde or achiral ketone via addition of fluorinated reagents is another means of access to fluorinated compounds. Trifluoromethyl trimethylsilane [(CF SiCFs] has been used by Pra-kash et al.87 as an efficient reagent for the trifluoromethylation of carbonyl compounds. Reaction of aldehydes or ketones with trifluoromethyltrime-thylsilane can be facilitated by tetrabutyl ammonium fluoride (TBAF). In 1994, Iseki et al.88 found that chiral quaternary ammonium fluoride 117a or 117b facilitated the above reaction in an asymmetric manner (Scheme 8-42). 

Scheme 8-42. Asymmetric trifluoromethylation of carbonyl compounds by chiral quaternary ammonium fluorides.

The first promising asymmetric aldol reactions through phase transfer mode will be the coupling of silyl enol ethers with aldehydes utilizing chiral non-racemic quaternary ammonium fluorides,1371 a chiral version of tetra-n-butylammonium fluoride (TBAF). Various ammonium and phosphonium catalysts were tried138391 in the reaction of the silyl enol ether 41 of 2-methyl-l-tetralone with benzaldehyde, and the best result was obtained by use of the ammonium fluoride 7 (R=H, X=F) derived from cinchonine,1371 as shown in Scheme 14. 

A. Ando, T. Miura, T. Tatematsu, T. Shioiri, Chiral Quaternary Ammonium Fluoride. A New Reagent for Catalytic Asymmetric Adol Reactions , Tetrahedron Lett. 1993, 34,1507-1510. 

T. Shioiri, A. Bohsako, A. Ando, Importance of the Hydroxymethyl-quinudidine Fragment in the Catalytic Asymmetric Adol Readions Utilizing Quaternary Ammonium Fluorides derived from Cinchona Akaloids , Heterocycles 1996, 42, 93-97. 

K. Iseki, T. Nagai, Y. Kobayashi, Asymmetric Trifluoro-methylation of Aldehydes and Ketones with Trifluoro-methyltrimethylsilane Catalyzed by Chiral Quaternary Ammonium Fluorides , Tetrahedron Lett. 1994, 35, 3137-3138. 

Carbonyl Addition Diethylzinc has been added to benzaldehyde at room temperature in the presence of an ephedra-derived chiral quat (8) to give optically active secondary alcohols, a case in which the chiral catalyst affords a much higher enantioselectivity in the solid state than in solution (47 to 48, Scheme 10.6) [30]. Asymmetric trifluoromethylation of aldehydes and ketones (49 to 50, Scheme 10.6 [31]) is accomplished with trifluoromethyl-trimethylsilane, catalyzed by a quaternary ammonium fluoride (3d). Catalyst 3d was first used by the Shioiri group for catalytic asymmetric aldol reactions from silyl enol ethers 51 or 54 (Scheme 10.6) [32]. Various other 1,2-carbonyl additions [33] and aldol reactions [34] have been reported. 

Reduction The asymmetric reduction of a series of aryl alkyl ketones with quaternary ammonium fluorides and silanes was reported by Drew and Lawrence [55]. In these reactions, the best catalysts (e.g., 6f) were from the qui ni ne/quinidine series in fact, a fluoride salt prepared from cinchonine gave no induction. The use of trimethoxysilane resulted in faster rates but lower enantioselectivites when compared with tris(trimethoxy)silane. It is interesting that, with the... 

Chiral Quaternary Ammonium Fluorides for Asymmetric Synthesis... 

The usefulness of the present system was then demonstrated by its application to the in-situ generation of structurally rigid, C2-symmetric chiral quaternary ammonium fluorides of type 6 (X = F) from the corresponding hydrogen sulfate 6 (X = H S04), and their direct use for the asymmetric aldol reactions (Scheme 9.3). For instance,... 

Table 9.1 Asymmetric Mukaiyama-type aldol reactions of a glycine derivative catalyzed by in situ-generated chiral quaternary ammonium fluoride.

Chiral Quaternary Ammonium Fluorides Preparation and Application to Organocatalytic Asymmetric Reactions... 

Currently, it is fair to say that asymmetric synthesis using chiral quaternary ammonium fluorides remains an underdeveloped field, and the various useful stereoselective carbon-carbon bond-forming processes described in this chapter are only the start of an exploration of the vast synthetic potential of this process, particularly when combined with current knowledge of organosilicon chemistry. It seems that the key issue to be addressed is the rational molecular design of chiral quaternary ammonium cations with appropriate steric and electronic properties. These are expected to be readily tunable to impart not only a sufficient reactivity but also an ideal chiral environment to the requisite nucleophile involved in a desired chemical transformation. Clearly, the continuous accumulation of information related to the structure of fluoride salts and their reactivity and selectivity should create a solid basis for this field, offering - in time - a unique yet reliable tool for sophisticated bond construction events with rigorous stereocontrol, under mild conditions. 

Quaternary Ammonium Fluoride-Mediated Mukaiyama-Type Asymmetric Aldol Reaction [4] (p. 122)... 

Worth mentioning are chiral gold complexes [20d, e] as well as chiral quaternary ammonium fluorides [21], which are used successfully as catalysts in the asymmetric aldol reaction. 

Palomo C, Oiarbide M, Garcia JM. Current progress in the asymmetric aldol addition reaction. Chem. Soc. Rev. 2004 34 3-15. Ooi T, Maruoka K. Asymmetrix organocatalysis of structurally well-defined chiral quaternary ammonium fluorides. Acc. Chem. Res. 2004 37 526-533. 

Reviews on phase-transfer catalysis for the syntheses of a-amino acids, (a) Ooi, T. and Maruoka, K. (2004) Asymmetric organocatalysis of structurally well-defined chiral quaternary ammonium fluorides. Acc. Chem. Res., 37, 526-533 (b) Maruoka, K. and Ooi, T. (2003) Enantioselective amino acid synthesis by chiral phase-transfer catalysis. Chem. Rev., 103, 3013-3028 (c) Ooi, T. and Maruoka, K. (2003) Enantioselective synthesis of a-amino acids by chiral phase-transfer catalysis. Yuki Gosei Kagaku Kyokaishi (J. Synth. Org. Chem.) 61, 1195-1206. 

Lewis add complexes formed by the reactions of various aminoalcohols with Et2AlG [778, 824] or by the reaction of Et2Zn with a chiral sulfamide [806] have displayed a low efficiency in the asymmetric condensations of ketene and thioketene silyiacetals derived from acetic acid with aldehydes. Disappointing se-lectivities have also been observed with some binaphtol-titanium complexes [778]. However, Mikami and Matsukawa [1296] recently performed the enantioselective condensation of various aldehydes with acetic acid derivatives in the presence of a chiral binaphtol-titanium complex. Good selectivities were observed when the reaction was performed at 0°C in toluene (Figure 6.95). Quaternary ammonium fluorides derived from cinchona alkaloids have been proposed as catalysts to perform additions of enoxysilanes derived from ketones to PhCHO, but the observed selectivities are modest [1303],... 

Trifluoromethylation. Carbonyl compounds are converted into the trifluoro-methyl carbinols in excellent yields by this reagent in the presence of a quaternary ammonium fluoride. Moderate asymmetric induction is observed when a chiral catalyst is used. 

Sn2 fluorination reactions are conducted in the presence of quaternary ammonium fluorides (substitution of other halogens) or in the presence of DAST or Deoxo-Huor (substitution of hydroxyl group) to provide the corresponding fluoro derivatives with inversion of configuration. Although widely used, this approach is not an asymmetric synthesis in the strict sense. In contrast to asymmetric electrophilic... 

Aldol and Related Condensations As an elegant extension of the PTC-alkylation reaction, quaternary ammonium catalysts have been efficiently utilized in asymmetric aldol (Scheme 11.17a)" and nitroaldol reactions (Scheme ll.lTb) for the constmction of optically active p-hydroxy-a-amino acids. In most cases, Mukaiyama-aldol-type reactions were performed, in which the coupling of sUyl enol ethers with aldehydes was catalyzed by chiral ammonium fluoride salts, thus avoiding the need of additional bases, and allowing the reaction to be performed under homogeneous conditions. " It is important to note that salts derived from cinchona alkaloids provided preferentially iyw-diastereomers, while Maruoka s catalysts afforded awh-diastereomers. 

The nitroaldol reaction of silyl nitronates with aldehydes promoted by ammonium fluorides, which was originally introduced by Seebach and Colvin in 1978 [24], is a useful method for the preparation of 1,2-functionalized nitroalkanols. Recently, the present authors have succeeded in developing an asymmetric version of high efficiency and stereoselectivity by using a designer chiral quaternary ammonium bifluoride of type 6 as catalyst, which was readily prepared from the corresponding bromide by the modified method C in Scheme 9.5 [25]. 

Both experimental and theoretical studies have been reported of fluoro-denitration and fluoro-dechlorination reactions using anhydrous tetrabutylammonium fluoride in DMSO. The absences of ion pairing and strong solvation are critical in contributing to the reactivity of the fluorinating agent24 Quaternary ammonium salts derived from cinchona alkaloids have been shown to be effective catalysts in an improved asymmetric substitution reaction of /1-dicarbonyl compounds with activated fluoroarenes. The products may be functionalized to yield spiro-oxindoles.25... 

Aldol reactions using a quaternary chinchona alkaloid-based ammonium salt as orga-nocatalyst Several quaternary ammonium salts derived from cinchona alkaloids have proven to be excellent organocatalysts for asymmetric nucleophilic substitutions, Michael reactions and other syntheses. As described in more detail in, e.g., Chapters 3 and 4, those salts act as chiral phase-transfer catalysts. It is, therefore, not surprising that catalysts of type 31 have been also applied in the asymmetric aldol reaction [65, 66], The aldol reactions were performed with the aromatic enolate 30a and benzaldehyde in the presence of ammonium fluoride salts derived from cinchonidine and cinchonine, respectively, as a phase-transfer catalyst (10 mol%). For example, in the presence of the cinchonine-derived catalyst 31 the desired product (S)-32a was formed in 65% yield (Scheme 6.16). The enantioselectivity, however, was low (39% ee) [65],... 

The asymmetric organocatalytic transformation of a ketone into an alcohol may be realized with the combination achiral silanexhiral phase-transfer catalyst, such a quaternary ammonium salt. The final alcohol is then recovered by an additional hydrolytic step. The asymmetric reduction of aryl alkyl ketones with silanes has been reported (ee-values up to 70%), the catalysts utilized being ammonium fluorides prepared from the quinine/quinidine series (e.g., 18 in Scheme 11.6) [19]. (For experimental details see Chapter 14.21.1). The more appropriated silanes were (Me3SiO)3SiH or (MeO)3SiH (some examples are... 

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