Trifluoromethylation of boronic acids

Ye Y, Sanford MS (2012) Merging visible-light photocatalysis and transition-metal catalysis in the copper-catalyzed trifluoromethylation of boronic acids with CF3I. J Am Chem Soc 134 9034-9037... 

Chu L, Qing FL. Copper-mediated oxidative trifluoromethylation of boronic acids. Org. Lett. 2010 12 5060-5063. 

Scheme 15.97 Cu-mediated trifluoromethylation of boronic acids with TMSCF3.

There are several different routes to carboxamides. In most of these reactions, a carboxylic acid is converted to a more reactive intermediate, e.g. the acid chloride, which is then allowed to react with an amine. For practical reasons, it is preferable to form the reactive intermediate in situ. Arylboronic acids with electron-withdrawing groups such as (3,4,5-trifluorophenyl)boronic acid act as highly efficient catalysts in the amidation between carboxylic acids and amines. (3-Nitrophenyl)boronic acid and [3,5-bis(trifluoromethyl)phenyl]boronic acid are also effective eimidation catalysts and commercially available. 

The proposed mechanism of the boron-catalyzed amidation is depicted in the Figure. It has been ascertained by H NMR analysis that monoacyloxyboronic add 1 is produced by heating the 2 1 mixture of 4-phenylbutyric add and [3,5-bis(trifluoromethyl)phenyl]boronic acid in toluene under reflux with removal of water. The corresponding diacyloxyboron derivative is not observed at all. When 1 equiv of benzylamine is added to a solution of 1 in toluene, the amidation proceeds even at room temperature, but the reaction stops before 50% conversion because of hydrolysis of 1. These experimental results suggest that the rate-determining step is the generation of 1. 

BLA 4 (Fig. 5) is one of the best catalysts for the enantio- and earo-selective cycloaddition of a-substituted a,/3-enals with highly reactive dienes such as cyclopen-tadiene. The corresponding reactions of a-unsubstituted a,)8-enals such as acrolein and crotonaldehyde are, however, characterized by low enantioselectivity and/or reactivity. The range of dienophiles that can be used with less reactive dienes is quite limited. The use of arylboronic acid with electron-withdrawing substituents such as [3,5-bis(trifluoromethyl)phenyl]boronic acid in the preparation of BLA greatly enhances... 

Figure 6. The dependence on additional water of the distribution ratio of boron atoms in a solution of [3,5-bis(trifluoromethyl)phenyl]boronic acid.

CAB 2, R = H, derived from monoacyloxytartaric acid and diborane is also an excellent catalyst (20 mol %) for the Mukaiyama condensation of simple enol silyl ethers of achiral ketones with various aldehydes. The reactivity of aldol-type reactions can, furthermore, be improved, without reducing the enantioselectivity, by use of 10-20 mol % of 2, R = 3,5-(CF3)2C6H3, prepared from 3,5-bis(trifluoromethyl)phenyl-boronic acid and a chiral tartaric acid derivative. The enantioselectivity could also be improved, without reducing the chemical yield, by using 20 mol % 2, R = o-PhOCgH4, prepared from o-phenoxyphenylboronic acid and chiral tartaric acid derivative. The CAB 2-catalyzed aldol process enables the formation of adducts in a highly diastereo- and enantioselective manner (up to 99 % ee) under mild reaction conditions [47a,c]. These reactions are catalytic, and the chiral source is recoverable and re-usable (Eq. 62). 

X-(Trifluoromethyl)ethenyl boronic acid (72) was conveniently prepared from the reaction of readily available 2-bromotrifluoropropene with alkyl borate and magnesium in one-pot. The Suzuki coupling of 2-amino-3-methoxy-5-bromopyrazine (71) with boronic acid 72 provided styrene derivative, 73 in excellent yield [43]. 

Some articles have described synthesis of 3-trifluoromethylquinoline (271) [161-165]. Catalytic oxidative trifluoromethylation of 3-qunolineboronic acid (270) resulted in 3-trifluoromethylquinoline in 49 % yield [161]. Use Togni s reagent (272) in reaction with boronic acids 270 resulted in increase yield of 271 up to 53 % [162]. 3-Trifluoromethylquinoline was also obtained by reaction of boronic acids 270 with CF3I [163] or with trifluoromethyl sulfonium salts [164] in 87 % yield. Interaction of 3-iodoquinoline (273) with sodium trifluoromethyl formate at presence Cu and AgjO also led to compound 271 [165] (Scheme 80). 

Molander had developed methods to trifluoromethylate organotri-fluoroborates utilising copper and NaSOaCFs (Langlois reagent) and TBHP (Scheme 18.30). Sanford has developed a similar copper mediated tri-fluormethylation of boronic acids (Scheme 18.31). ... 

Jiang has described the successful preparation of a-(trifluoromethyl)ethenyl boronic acid by reaction of readily available 2-bromotrifluoropropene, magnesium and an alkyl borate in an one-pot process [89]. The trifluoromethyl boronic add 111, thus obtained, was found to be stable for several months even in the presence of air and moisture (Scheme 3.57). 

Molybdenum hexafluoride, in the presence of boron trifluonde, reacts with acetic acid and haloacetic acids at 130-160 °C to give respectively, 1,1,1 tri fluoroethane and 1,1 1 trifluorohaloetlianes in 60-89% yields [2d0, 241] Prolonged treatment of pyridine mono and dicarboxylic acids with an excess of molybdenum hexafluoride at elevated temperatures provides the respective mono-and bis(trifluoromethyl)pyridines in good yields [241] (equation 127)... 

Enantioselective D-A reactions of acrolein are also catalyzed by 3-(2-hydroxyphenyl) derivatives of BINOL in the presence of an aromatic boronic acid. The optimum boronic acid is 3,5-di-(trifluoromethyl)benzeneboronic acid, with which more than 95% e.e. can be achieved. The TS is believed to involve Lewis acid complexation of the boronic acid at the carbonyl oxygen and hydrogen bonding with the hydroxy substituent. In this TS tt-tt interactions between the dienophile and the hydroxybiphenyl substituent can also help to align the dienophile.114... 

Trifluoromethylation of Enolate Anions with a Suitable Combination of Boron Lewis Acids (94JOC5692)... 

Trifluoromethylation of enolates could be achieved by complexing the enolate with boron Lewis acids (Equation 118). The best boron Lewis acid for this purpose was 2-phenyl-l,3,2-benzodioxaborole 231. For enantio-selective trifluoromethylation, the optically active boron compound 232 was used (Equation 119). 

Acyl aryl boron species also react with amines to yield amides with mixed results. Eor example, catecholborane was used to generate lactams successfully (46). Aryl boronic acids with electron-withdrawing groups, such as 3,4,5-trifluorobenzene-boronic acid and 3,5-bis-(trifluoromethyl)benzeneboronic acid, can act efficiently as an amidation catalyst when added to a mixture of acid and amine (47). 

Support for this concept is provided by H NMR studies which have identified a downfield resonance of the hydrogen-bonded proton in this pair at 18 ppm in ch3miotrypsinogen and chymotrypsin at low pH and at 14.9-15.5 ppm at high pH values.Similar resonances are seen in the a-lytic protease, in sub-tilisin, in adducts of serine proteases with boronic acids or peptidyl trifluoromethyl ketones, in alkylated derivative of the active site histidine, and in molecular complexes that mimic the Asp-His pair in the active sites of serine pro teases. 

Asymmetric hydrogenation of either a carbonyl or an imino group to a hydroxyl group or an amino group has frequently been employed for the introduction of chirality in amino acid syntheses. Corey s catecolborane-oxazaborolidine protocol enables transformation of difluoromethyl ketone 1 into alcohol 2 with excellent enantioselectivity. The reaction of diastereoselective amination of a-hydroxyaldehyde 3 with A,A-diallylamine and 2-furyl-boronic acid provides furyl amino alcohol 4 in good chemical yield along with excellent diastereoselectivity. This protocol is applicable for the preparation of amino acids and amino alcohols with a trifluoromethyl group by the combination of /V,/V-diallyl or N,N-dibenzyl amine and aromatic, heteroaromatic and alkenyl boronic acids [7]. The usual chemical transformations as shown in steps 5 to 8 in Scheme 9.1 lead to (2S,3R) difluorothreonine 5 [8]. 

In recent years, catalytic asymmetric Mukaiyama aldol reactions have emerged as one of the most important C—C bond-forming reactions [35]. Among the various types of chiral Lewis acid catalysts used for the Mukaiyama aldol reactions, chirally modified boron derived from N-sulfonyl-fS)-tryptophan was effective for the reaction between aldehyde and silyl enol ether [36, 37]. By using polymer-supported N-sulfonyl-fS)-tryptophan synthesized by polymerization of the chiral monomer, the polymeric version of Yamamoto s oxazaborohdinone catalyst was prepared by treatment with 3,5-bis(trifluoromethyl)phenyl boron dichloride ]38]. The polymeric chiral Lewis acid catalyst 55 worked well in the asymmetric aldol reaction of benzaldehyde with silyl enol ether derived from acetophenone to give [i-hydroxyketone with up to 95% ee, as shown in Scheme 3.16. In addition to the Mukaiyama aldol reaction, a Mannich-type reaction and an allylation reaction of imine 58 were also asymmetrically catalyzed by the same polymeric catalyst ]38]. 

Steric bulkiness of substituents in ketones (25), for example, makes it possible to differentiate two pairs of lone-pair electrons (a or b in 25) on carbonyl oxygen for coordinating with the Lewis acidic center of boron in oxazaborolidine (28). The complex (29) formed from 28 with catecholborane binds ketone (32) stereospecifically by using the lone-pair electrons at the less hindered side so as to direct the smaller substituent Rs toward the bulky N-tert-butyl group. The intramolecular hydride transfers to the favorably coordinated carbonyl group as shown in 30, Scheme 1.82, results in asymmetric reduction of ketones. Reduction of trifluoromethyl and methyl ketones (25) (R = CF3 or CH3) by this system afforded the corresponding alcohols (26 or 27) with an opposite stereochemistry (Scheme 1.82). 

Since the first asymmetric reduction of ketones with chiral borohydrides by Itsuno et al. [ 1 ], a number of studies on the asymmetric reduction of ketones with chiral borane reagents have been demonstrated [2]. Corey s oxazaborolidines are some of the most successful reagents [3 ]. The effect of fluorine substituents was examined in the asymmetric reduction of acetophenone with LiBH4 by the use of chiral boronates (73) obtained from substituted phenyl boronic acid and tartaric acid [4]. Likewise, 3-nitro, fluorine, and trifluoromethyl groups on the 3- or 4-position provided enhanced stereoselection (Scheme 5.20). 

Recently, catalytic asymmetric Diels-Alder reactions have been investigated. Yamamoto reported a Brdnsted-acid-assisted chiral (BLA) Lewis acid, prepared from (R)-3-(2-hydroxy-3-phenylphenyl)-2,2 -dihydroxy-1,1 -binaphthyl and 3,5-Z7ri(trifluoromethyl)-benzeneboronic acid, that is effective in catalyzing the enantioselective Diels-Alder reaction between a,P-enals and various dienes. The interesting aspect is the role of water, THE, and MS 4A in the preparation of the catalyst (Eq. 12.19). To prevent the trimerization of the boronic acid during the preparation of the catalyst, the chiral triol and the boronic acid were mixed under aqueous conditions and then dried. Using the catalyst prepared in this manner, a 99% ee was obtained in the Diels-Alder reaction... 

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