Alkyl trifluoroborates,

Scheme 2.39 Suzuki-Miyaura cross-coupling reactions of functionalized primary alkyl trifluoroborates.

Recently, the van den Hoogenband and Molander groups [122] independently devdoped the Pd-catalyzed Suzuld-Miyaura cross-couphng reaction of secondary alkyl trifluoroborates with various aryl hahdes (Eq. (43), Scheme 2.40). Molander s... 

Preparation and B-alkyl-Suzuki-Miyaura Cross-coupling Reactions of Functionalized Alkyl Trifluoroborates... 

Scheme 3.82 Preparation and Pd-catalyzed Suzuki cross-coupling of functionalized alkyl trifluoroborates.

Scheme 3.83 Suzuki cross-coupling reactions of functionalized alkyl trifluoroborates with triflates.

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. 

The Suzuki Coupling, which is the palladium-catalysed cross coupling between organoboronic acid and halides. Recent catalyst and methods developments have broadened the possible applications enormously, so that the scope of the reaction partners is not restricted to aryls, but includes alkyls, alkenyls and alkynyls. Potassium trifluoroborates and organoboranes or boronate esters may be used in place of boronic acids. Some pseudohalides (for example triflates) may also be used as coupling partners. 

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]. 

Boronic acids and 9-BBN derivatives are often used as alkyl partners, but trifluoroborates may be more convenient and stable. Introduction of a protected aminoethyl chain, using a trifluoroborate, has substantial potential for bioactive molecules - the reaction shown below using 3-bromopyridine works equally well for pyrimidine (C-5), thiophene (C-2), and indole (C-5). ... 

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

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. 

Synthesis of Alkyl/Aryl Trifluoroborates Using KHF2.749... 

The generation of an iminium ion of a, 3-unsaturated carbonyl compounds lowers the LUMO energy. As a result, the cx-CH acidity increases as well as the ability to participate in conjugate additions. The first organocatalyzed 1,4-addition to a,j3-unsaturated aldehydes was reported by the MacMillan group [78]. For theoretical explorations of the configurative outcome of Michael additions of pyrroles and indoles to crotonaldehyde see Reference [79]. This transformation has been widely used in Friedel-Crafts alkylations of a,(5-unsaturated carbonyl compounds (see Reference [lb] and reports cited therein). Comparable examples of this transformation with ( )-crotonaldehyde in the intermolecular series were found in aryl alkylation with trifluoroborate (58 and 60) [80], indole alkylation (62) [81], Friedel-Crafts alkylation of electron-rich benzenes (64) [82], and Friedel-Crafts alkylation with phosphonates (65) [83] (Scheme 4.21). 

Lee S, MacMillan DWG Organocatalytic vinyl and Friedel-Grafts alkylations with trifluoroborate salts. J. Am. Chem. Soc. 2007 129(50) 15438-15439. 

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