Trifluoroborates, alkenyl

A novel method for the convenient synthesis of alkenyl fluorides 15, as well as diflu-oromethyl-substituted alcohols 16 and amides 17, via electrophilic fluorination with one equivalent of F-Teda BF4 (6) of alkenyl boronic acids and trifluoroborates, has been reported.87 The alkenyl fluorides 15 are obtained as Z/E mixtures when the reaction is carried out with one equivalent of F-Teda BF4 in acetonitrile at room temperature. When the reaction is performed with two equivalents of F-Teda BF4 in water or a nitrile solvent the difluoromethyl-substituted alcohols 16 or amides 17, respectively, are obtained. 

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. 

A-(4-Pentenyl)iodoacetamides (i.e., 142 and 145) underwent atom transfer radical cyclization reactions in the presence of trifluoroborate etherate at room temperature, usually with an excellent 8-endo regioselectivity (Schemes 59 and 60 <2005JOC1539>). It was thus shown that 8-endo cyclization of iV-alkenyl a-carbamoyl radicals is an intrinsically favored process easily promoted by a Lewis acid, such as BF3-OEt2. 

The reactions take place under mild conditions with good to high yields. Another important advantage is the use of relatively nontoxic reagents. In the synthesis of the alkenyl fluorides, mixtures of Z/E isomers are obtained. The substrate trifluoroborates can be prepared from the corresponding boronic acids by reaction with potassium hydrogen fluoride/water. ... 

A formal total synthesis of oximidine II was achieved by G.A. Molander et al., using an intramoiecuiar Suzuki-type cross-coupiing between an alkenyl potassium trifluoroborate and an alkenyl bromide to construct the highly strained, polyunsaturated 12-membered macrolactone core of the natural product. " The stability of potassium trifluoroborates was exploited in order to establish the best conditions for the macrocyclization. 

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, ... 

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

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

More recently, it was reported that potassium alkenyl and aryl-trifluoroborates undo go similar addition to enones in the presence of a Rh(I) catalyst (Schemed) (ii). It was found that the reaction proceeds more rapidly than with the corresponding boronic acids, and the choice of catalyst ligand does not signifrcantly influence the overall catalyst efficiency. 

Batey and Quach have investigated alkenyl and aryl trifluoroborate salts as coupling agents. Their earlier publication [47], disclosed a C-O cross-coupling protocol... 

Molander, G. A., Bernard , C. R. 2002. Suzuki-Miyaura cross-coupling reactions of potassium alkenyl-trifluoroborates. J. Org. Chem. 67 8424—8429. 

The Molander group reported a formal total synthesis of oximidine II, in which an intramolecular Suzuki cross coupling between an E-alkenyl potassium trifluoroborate and aZ,Z-dienyl bromide constructed the highly strained 12-membered macrolactone core of the natural product (Fig. 7) [22]. Importantly, the stereochemistry of the starting partners was conserved to deliver the ,Z,Z-conjugated triene in the natural product. 

Rhodium(I)-complexes are known to be excellent catalysts for the conjugate additions of aryl- and alkenyl boronic acids to a,/3-unsaturated ketones, esters and amides [73,74]. Batey has recently prepared aryl and alkenyl trifluoroborates as air-and moisture-stable reagents for the nucleophilic addition to enones in the presence of a Rh(I)-catalyst to give /3-functionalized ketones in good yields [75]. A number of aryl fluoroborates with electron-withdrawing substituents were also tolerated in this reaction. An unprecedented Rh-catalyzed 1,4-addition of aryl boro-... 

Synthesis and Palladium-catalyzed Cross-coupling Reactions of Functionalized Alkenyl Trifluoroborates... 

Cross-coupling reactions of functionalized alkenyl trifluoroborates 124 with 4-bro-mobenzonitrile in the presence of catalytic amounts of PdCl2(dppf) has been studied by Molander [97,98], Herein functionalized 4-cyanostyrenes of type 125 were obtained in satisfactory yields (Scheme 3.64). 

Scheme 3.64 Preparation and cross-coupling reactions of functionalized alkenyl trifluoroborates.

---