Heck coupling reactions asymmetric arylation

In a related study, the Shibasaki group examined cyclizadon of naphthyl triflate 10.1 (Scheme 8G.10) [23], Cyclization of 10.1 under standard cationic conditions gave Heck product 10.2 in 78% yield and 87% ee. Evidently, the reaction is fairly tolerant of the nature of the aryl group, because both 10.1 and 9.3 behaved similarly. An interesting variation of this reaction was also demonstrated in which Suzuki coupling and asymmetric Heck cyclization were performed in a one-pot operation. Thus, treatment of ditriflate 10.3 with borane 10.4 under standard Heck conditions provided 10.2 in similar enantioselectivity to the stepwise procedure, albeit in quite low yield. Heck product 10.2 was converted in several steps to the natural products, halenaqui-none (10.5) and halenaquinol (10.6). 

Mizorokf and Heck reported independently in the early 1970s the first palladium-mediated coupling of an aryl or vinyl halide or triflate with an alkene. This reaction is generally referred to as the Heck reaction. From the first reports on asymmetric intramolecular Heck reactions by Overman and Shibasakf in 1989 the asymmetric Heck reaction has emerged as a reliable method for the stereoselective formation of tertiary and quaternary stereogenic centers by C-C bond formation in polyfunctionalized molecules. ... 

Thus, traMi-3-alkyl-6-(phthalimido)cyclopentenes were prepared in excellent to modest yields from the corresponding tran -chloroalkene by the palladium coupling reaction [84d]. Inexpensive and efficient Pd-TMG systems, Pd(OAc)2-TMG or PdC -TMG, have been developed for the Heck reaction of an olefin with an aryl halide, in which TMG (1) acts as a ligand [84e]. In the reaction of iodobenzene with butyl acrylate the turnover numbers were up to 1000000. TMG (1) was used as a base for the palladium catalysed asymmetric Wagner-Meerwein shift of nonchiral vinylcyclopropane and cyclobutane derivatives leading to asymmetric synthesis of cyclobutanones, cyclopentenones, y-butyrolactones and 5-valerolactones [85] (Scheme 4.34). Replacement of TMG (1) with an inorganic bases such as lithium or cesium carbonate resulted in little effect. 

In a narrower sense, this review covers intramolecular Mizoroki-Heck [1] reactions forming carbocycles [2] that is, the palladium-catalyzed intramolecular coupling of vinyl/aryl (pseudo-)halides with an alkene tethered by a hydrocarbon chain. Ring closures furnishing heterocycles are covered in Chapter 6 also beyond the scope of this chapter are the domino/cascade or tandem (Chapter 8) and asymmetric processes (Chapters 12 and 16) dealing with formation of a carbocycle. 

Using NMR the same authors have identified several intermediates in the asymmetric Heck arylation of dihydrofuran [23, 24]. Reaction of the Binap salt, 30, with 2,3-dihydrofuran below 233 K gave salt 31 as the single species (see Figure 1.8). A parallel reaction between 30 and [2- H] 2,3-dihydrofuran confirmed the structure. At 243 K, 31 slowly decomposed to form 32 and 32 with concomitant release of the coupling product 33 (91% ee). 

As mentioned previously, the partially reduced forms of five membered heteroaromatic systems might act as olefins in insertion reactions. This behaviour is characteristic particularly of dihydrofuranes. The olefin insertion and the following / hydride elimination should in principle lead to a trisubstituted olefin, which is rarely observed, however. Typical products of this reaction are 2-aryl-2,3-dihydrofuranes. A characteristic example of such a reaction is presented in 6.54. The coupling of 4-iodoanisole and dihydrofurane led to the formation of the chiral 2-anisyl-2,3-dihydrofurane in excellent yield.83 The shift of the double bond, which leads to the creation of a new centre of chirality in the molecule, opens up the way for enantioselective transformations. Both intermolecular and intramolecular variants of the asymmetric Heck reaction have been studied extensively.84... 

Prior chapters have covered the use of transition metals in asymmetric hydrogenations ( 6.2 and 7.1), hydroborations ( 7.3), hydrosilylations and hydro-cyanations ( 6.3, 6.4, 7.4 and 7.5), cyclopropanations ( 7.19), aldol reactions ( 6.11), allylations of carbanions ( 5.3.2), and some sigmatropic rearrangements ( 10.3). This chapter covers other reactions catalyzed by transition metal complexes including coupling of organometallic reagents with vinyl, aryl or allyl derivatives, Heck reactions allylamine isomerizations, some allylation reactions, car-bene insertions into C-H bonds and Pauson-Khand reactions. 

Two new fluorous chiral 2,2 -bis(diphenylphosphino)-1,1 -binaphthyl (BINAP Table 15.1, entries 11 and 12) ligands were synthesized and their efficiency was demonstrated in an asymmetric Mizoroki-Heck reaction (Scheme 15.8) [74-76]. Aryl triflates 38 were coupled with 2,3-dihydrofuran (39) to (i )-40 in up to 93% ee. Either pure fluorous solvents or mixtures of fluorous and nonfluorous solvents were applied. Ligand 34 was compared with conventional BINAP, with the fluorous ligand giving lower reaction rates and a similar level of enantioselectivity in 24-77 h reaction time [74, 75]. The catalyst could not be recovered by reverse-phase silica gel chromatography due to its oxidation. 

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