Trifluoroborate salts

Other unidentified oxidation products are obtained. In view of their unique properties, interest in the chemistry of trif luoroborate salts is expected to grow further. 

Ni-catalyzed Suzuki-Miyaura cross-coupling reaction [55a, 56a, 84k], allowing cheaper and more stable electrophiles to be utilized. 

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A major limitation of these alkylation reactions has been the regiospecificity and/or need for directing groups of the nucleophile. MacMillan has overcome this and expanded the scope of the reaction to include alkene nucleophiles by using trifluoroborate salts (Scheme 18) [87]. This approach enables alkylation of the 2-position of indoles, complimenting the 3-selective alkylation shown in Scheme 16. One equivalent of hydrogen fluoride was found to be necessary in the reaction in order to sequester the boron trifluoride generated. 

Finally, in a dramatic example of chemoselectivity, potassium 1-alkenyltrifluoroborates can be epoxidized readily using DMDO to yield highly functionalized trifluoroborate salts (Scheme 18) <2003JA11148>. 

Molander has published a series of papers demonstrating the utility of potassium alkyl, alkenyl-, alkynyl-, and aryltrifluoroborates in palladium coupling reactions. The crystallinity and air-stability of these trifluoroborate salts make the use of these an interesting alternative to the use of boronic acids or esters. Good yields have been obtained in several related palladium coupling processes, which are most easily classified as Suzuki couplings. The broad applicability of this process is demonstrated by the production of 58 [40], 59 [41], and 60 [42]. 

The use of trifluoroborate salts in couplings, which are very easily prepared from boronic acids by reaction with KHF2, is a useful variant of the Suzuki reaction. These salts have the advantage of enhanced (often considerably) stabihty compared to boronic acids and this is particularly notable for alkenyl compounds, which can be stored for a considerable time. The coupling conditions are very similar to those for boronates and are apphcable to a wide range of heterocyclic substrates, ... 

Arylation of indoles can also be carried out via arylpalladium acetates generated from boronic acids or trifluoroborate salts " and palladium acetate. The reactions are catalytic in palladium, cycling of the Pd(ll) being effected by the use of a re-oxidant (Cu(ll)/air). The reaction works well on NH and A-methyl indoles but fails with the A-acetyl derivative. 

Also in the alkenyl group transfer from the trifluoroborate salts to dichloroalkyl aldimines BF3 OFt2 plays an activating role. ... 

Instead of aryl halides, arenediazonium salts are also excellent arylating agents in the Suzuki coupling, although more hindered arylboronic acids did not react The reaction is catalysed by several sources of ligand-free palladium such as Pd(OAc)2, Pd2(dba)3 and Pd/C at room temperature in dioxane without any added base [98]. Use of potassium aryl trifluoroborate salts also allowed the introduction of more sterically hindered aryl groups [99]. 

Kabalka et al. have investigated the Pd-catalyzed eross-eoupling reaction of MBH acetates and bis(pinacolato)diboron to produee 3-substituted-2-alkoxy-carbonyl allylboronates 371, whieh ean be further transformed into stable allyl trifluoroborate salts 372 by addition of exeess aqueous KHF2. The allylboronate 371 and allyltrifluoroborate derivatives 372 react with aldehydes to afford functionalized homoallyhc alcohols 373 and 374, respectively, stereoselectively in the presence of Lewis acid (Scheme 3.166). ... 

Soon afterward, the same group accomplished the first asymmetric organo-SOMO a-vinylation of aldehydes using vinyl trifluoroborate salts (Scheme 8.30) [137]. Broad functional groups tolerance, high reaction efficiency, trawi-olefin selectivity, and enantioselectivity were obtained under optimized reaction conditions in the presence of imidazolidinone catalyst LXIV. Moreover, the steric demands of the aldehyde substrate have little influence on efficiency and enantiocontrol. This reported transformation also represents the first use of boron salts as coupling reagents for radical-based processes. 

Lee S, MacMillan DWC (2007) Organocatalytic Vinyl and Friedel-Crcfis Alkylations with Trifluoroborate Salts. J Am Chem Soc 129 15438... 

Scheme 2.24 Cross-coupling reactions of trifluoroborate salts to provide biaryls.

Cross-couphng reactions of heteroaromatics are especially valuable due to their importance in the pharmaceutical industry (see earlier discussion). In order to overcome the difficulties associated with cross-coupling these substrates, several powerful catalytic systems have been successfully developed and employed [33, 39, 40, 42]. In most of these methods, however, excess boronic acids is often required in order to overcome protodeboronation during the cross-coupling process. In most cases, 20-50% excess boronic acid must be employed to obtain a high yield of the desired product, as described in the previous section. Trifluoroborate salts, which release boronic acids slowly into the reaction mixture, present a potential solution to this problem (Eq. (24), Scheme 2.25). Indeed, Buchwald and coworkers... 

Utilized Pd(OAc)2 and SPhos 24 as the catalyst system to effectively catalyze Suzuki-Miyaura cross-couplings with only 1.1 equiv. of trifluoroborates [84e]. More recently, Molander and coworkers have developed a general cross-coupling system to many classes of heteroaromatic trifluoroborates employing Pd(OAc)2 and RuPhos 23 [84j]. Furan 135, thiophene 132, pyrrole 126, pyrazole 130, isoxazole 131, pyridine 127, pyrimidine 133, indole 129, benzothiophene 136, benzofuran 135, quinoline 128, and isoquinoUne could all be cross-coupled with only 1.04 equiv. of trifluoroborate salts, affording the corresponding cross-coupled products in good yield (Scheme 2.25). 

Scheme 2.26 Suzuki-Miyaura cross-coupling reactions of alkenyl substrates involving trifluoroborate salts.

Scheme 2.27 Orthogonality associated with trifluoroborate salts.

Another solution is to employ trifluoroborate salts 2.215, which can be prepared from the boronic acid by treatment with potassium hydrogen fluoride (Scheme 2.74). They can also be prepared from alkyl bo-ranes in a similar way (Scheme 2.75). These stable salts can be efficiently employed in Suzuki coupling reactions (Scheme 2.T6)P One application is in the synthesis of the unusual amino acid, trityrosine 2J26 (Scheme 2.77). In this synthesis an aryl diiodide 2.222 was coupled with a trifluoroborate salt 2.224 that had been formed by Miyaura borylation of iodide 2.223 followed by KHF2 treatment. Global debenzylation of coupling product 2.225 gave the product 2.226. Another example of the use of a trifluoroborate salt can be found in Scheme 2.88. 

The installation of a vinyl group by Suzuki coupling presents a particular problem because vinyl boronic acid is unstable, readily undergoing polymerization. In a smdy of vinylation in order to make a polymer precursor, the vinyl trifluoroborate salt was found to be effective, giving the cleanest product 2.228 on a 72 g scale (Scheme 2.78). ... 

Figure .17 Synthesis of dichloroboranes, monoalkylboranes, and trifluoroborate salts.

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