Stifle coupling

Only bromo- and iodopyrimidine provide sufficient activation for the Stifle coupling of a 5-halopyrimidines to take place. Undheim et al. discovered that sequential substitution of 5-bromo-2,4-dichloropyrimidine occurred according to the order of reactivity, 4-C1 > 5-Br > 2-C1. The regio- and chemoselectivity were elegantly demonstrated by stepwise introduction of three different substituents onto 5-bromo-2,4-dichloropyrimidine [33],... 

M. Hoshino, P. Degenkolb, D. P. Curran, Palladium-Catalyzed Stifle Couplings with Fluorous Tin Reactants , J. Org. Chem. 1997, 62, 8341. 

Furane derivatives, like pyrroles, couple effectively with acetylenes. In case both the a-, and / -position are available for the reaction, like in the case of 4,5-dibromo-furfural in 6.45., the cross-coupling takes place preferentially in the former position65 The observed selectivity is in line with other palladium catalyzed transformations of dihalofuranes, such as their Stifle coupling.66... 

Recently, Li successfully conducted the Suzuki and Stifle reactions on the pyrazine ring of 3-bromoquinoxalin-2-ylamines [51]. Indolylquinoxaline 92 was obtained from the union of 3-bromoquinoxalin-2-ylamine 90 and 1 -phenyIsulfonyl-2-tri-n-butylstannyl- 1/Tindole (91). A wide variety of heterocyclic stannanes bearing various functional groups underwent Stifle coupling with 90 under the same conditions to give the corresponding adducts in 72-98% yields. 

DC of acetylenes 6 and nitrile oxides, generated in situ from nitro compounds 5, afforded isoxazoles 7 directly (R3 = Ar) or through Stifle coupling with aryl iodides of the 5-... 

As well as labelling reagents permanently fluorous, Curran has also labelled substrates temporarily fluorous for multiplex synthesis. For example, a series of fluorous aryl tin substrates were prepared (Fig. 8) and used as variable pieces of a small library of Stifle couplings [86-88]. A mixture of tin reactant (32a-d, 1.2 equivalents), halide or triflate (35a-e, 2 mmol, 1 equivalent), PdCl2(PPh3)2 (2 mol%) and LiCl (3 equivalents) in THF/DMF (1/1,1 cm3) was heated at 80°C for 22 h. The reactions were carried out in groups of five by reacting one tin reactant with all five partners in separate vials simultaneously. After evaporation of the solvent, the crude... 

The mechanism is very similar to that of the Stifle coupling. Oxidative addition of the vinylic or aromatic halide to the palladium(O) complex generates a palladium(II) intermediate. This then undergoes a transmetallation with the alkenyl boronate, from which the product is expelled by reductive elimination, regenerating the palladium(O) catalyst. The important difference is the transmetallation step, which explains the need for an additional base, usually sodium or potassium ethoxide or hydroxide, in the Suzuki coupling. The base accelerates the transmetallation step leading to the borate directly presumably via a more nucleophilic ate complex. 

Stille reactions have also shown to be suitable for these flash heating conditions, and rapid and successful Stifle couplings were reported by Hallberg and Larhed in 1996 [Equation (5.3.21)]. ... 

The Stifle-Kelly reaction is a variant of the Stifle coupling where an organodihalide undergoes an intramolecular reaction in the presence of hexamethylditin and a palladium catalyst. 

Methyl-4-pyrone-3-triflate gives good yields in Stifle couplings, nnder microwave heating, with a range of heterocyclic stannanes." "... 

This oxazinonc route can be used to obtain bisaryl glycines by a version of the Stifle coupling reaction (equation III). 

Fluorous-phase soluble h < acryloxysuccinimide-containinj hence Wilkinson catalyst analog Miscellaneous reactions. solvents while employing a fl diaryl diselenide used to assist t A multicomponent coupling and rapid Stifle couplings are with microwave irradiation. 

A multicomponent coupling involving fluorous allyltin reagents has been reported, and rapid Stifle couplings are completed employing aryltris(polylfluoroalkyl)stannanes with microwave irradiation. ... 

One early example of microwave-assisted fluorous synthesis involved palladium-catalyzed Stifle couplings of fluorous tin reagents with aryl halides or triflates (Scheme 16.59) [90]. The desired biaryl products were isolated in good yields and purity after a three-phase extraction. Similar results were also achieved by use of so-called F-21 fluorous tags (CFl2CFl2CioF2i) on the tin reagent [91]. 

Polyurea-encapsulated palladium catalysts promote the phosphine-free Mizoroki-Heck reaction, which results in a high yield of cinnamates 46 (Scheme 86). The catalyst, which is easily recovered by filtration, is also applicable to the Suzuki-Miyaura and Stifle coupling reactions. 

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