2.3- dihydrofuran, asymmetric Heck

A novel phosphinito dipeptido ligand series were prepared, and fully characterized. These ligands readily form metal complexes with Pd(H) and Pt(II) precursors. The Pd(II) complexes were investigated for their suitability in asymmetric Heck reaction using 3,4-dihydrofuran as a substrate. 

Pd complexes 9-12 were tested for their catalytic behavior in the asymmetric Heck reaction involving the phenylation of 2,3-dihydrofuran (Scheme 3). The results are summarized in Table 2. The two isomeric products of 2-phenyl-2,5-dihydrofuran are formed with varying yields from 80% to 0%. The obtained ee s are high. Complex 12 is shown to be catalytically inactive. The lack of catalysis in complex 12 is rationalized by differences in the steric requirements between the diphenylphosphinites 1-3 (cone angle >140°) and the more sterically hindered cyclohexyl-phosphinite 4 (cone angle >170°) and the resulting stereochemistry on the Pd center. The ligands in complex 12 adopt a... 

Scheme 3 Asymmetric Heck coupling of 3,4-dihydrofuran and iodobenzene in the presence of Pd complexes 9-12 giving a mixture of regio and stereo isomers a) 2(R)-phenyl-2,3-dihydrofuran, b) 2(R)-phenyl-2,5-dihydrofuran c) 2(S)-phenyl-2,3-dihydrofuran d) 2(S)-phenyl-2,5-dihydrofuran.

A short five-step synthesis of a bifuran, namely ( )-2,2 -bis(diphenylphosphino)-3,3 -binaphtho[2,l-I>]furan (BINAPFu) from naphthofuranone via a low-valent titanium-mediated dimerization was reported. The newly developed resolution procedure for phosphines was utilized to provide the optically active bidentate phosphine ligands (BINAPFu), which consistently outperforms BINAP in the asymmetric Heck reaction between 2,3-dihydrofuran and phenyl triflate . Another way in which a benzofuranone can be converted into benzo[7 ]furan is by treatment of the former with 1-BU2AIH at -78°C followed by an acidic work up <00TL5803>. 

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... 

A similar procedure was employed in the asymmetric Heck-type coupling of iodonium salt 81 with 2,3-dihydrofuran (Scheme 38) [65]. When carried out in the presence of the chiral bidentate ligand (R)-BINAP, this reaction afforded optically active (up to 78% ee) coupling product 82 in moderate yield. 

Asymmetric Heck-type ary lotion.1 A catalyst prepared in situ from Pd(OAc)2 and (R)-BINAP effects a highly enantioselective arylation of 2,3-dihydrofuran with aryl triflates with diisopropylethylamine as base and benzene as solvent. Two products (2 and 3) are formed with opposite configurations. The highly enantioselective formation of the major product (2) is ascribed to a kinetic resolution step which converts the enantiomer of 2 into 3. 

In an interesting example of the first asymmetric Heck reaction,6 using sulfoxides as chiral auxiliaries, Carretero et al.145 have recently used a new chiral sulfoxide, obtained by the DAG methodology. The palladium-catalyzed arylations of 4-arylsulfinyl-2,3-dihydrofurans 102 have shown that the stereochemical outcome of the reaction is highly dependent on the substitution of the sulfoxide. Thus, independently of electronic substitution of the aryl iodide, different aryl sulfoxides... 

Excellent enantioselectivity and double-bond regioselectivity can be achieved in an asymmetric Heck reaction between 2,3-dihydrofuran and aryl triflates by using a combination of chiral diphosphine-oxazoline ferrocenyl ligand and Pd catalyst <03CEJ3073>, as shown below. Chiral diphosphine-containing (arene)tricarbonylchromium(O) complexes were also used as ligands for this reaction to obtain the 2,3-isomer, however, both the yield and enantioselectivity were modest <03TA1455>. 

Scheme 3-49 Ligand-induced asymmetric Heck coupling of 2,3-dihydrofuran [205-207],...

For intermolecular asymmetric Heck reaction between aryl triflates and 2,3-dihydrofuran the hindered diphosphine 1 is superior to BINAP. Improved enantioselectivity is due to the bulky f-butyl substituents to create a more ideal chiral pocket in the metal complexes. 

The intermolecular asymmetric Heck reaction, a palladium-catalysed carbon-carbon bond forming process, is an efficient method for the preparation of optically active cyclic compounds.[1] Very recently, a new catalytic system has been developed based on palladium complexes having l-[4-(5)-tert-butyl-2-oxazolin-2-yl]-2-(5)-(diphenylphosphino)ferrocene (1) as the chiral ligand121 (Figure 5.2), which we have shown to be efficient catalysts for the enantioselective intermolecular Heck reaction of 2,3-dihydrofuran (2).[3] In contrast to complexes derived... 

Hennessy, A.J., Malone, Y.M. and Guiry, PJ. (1999) 2,2-Dimethyl-2,3-dihydrofuran, a new substrate for intermolecular asymmetric Heck reactions. Tetrahedron Letters, 40, 9163-9166 Hennessy, A.J., Malone, Y.M. and Guiry, P.J. (2000) The asymmetric cyclohexenylation of 2,2-dimethyl-2,3-dihydrofuran. Tetrahedron Letters, 41,2261-2264 Hennessy, A.J., Connolly, D.J., Malone, Y.M. and Guiry, PJ. (2000) Intermolecular asymmetric Heck reactions with 2,2-diethyl-2,3-dihydrofuran. Tetrahedron Letters, 41, 7757-7761. 

The microwave-assisted asymmetric Heck reaction has also been used with success for intermolecular bond formation (Scheme 2.28). Using 2,3-dihydrofuran and phenyl triflate as model substrates, the most active catalyst screened was a combination of Pd2dba3 and a phosphine-thiazole supporting ligand. Heating a THF/DIPEA... 

Nakamura and co-workers synthesized a heavily fluorinated chiral BINAP, (R)-6,6 - bis(tris (1H, 1 H,2 H,2 H-perfluorooctyl) srlyl]-2,2 -bis (diphenylphosphino)-1,1 -binaphthyl ((R)- FJ3BINAP) (F content = 54%, partition coefficient benzene/FC-72 = 26 74, CH3CN/FC-72 = 2 98) and applied it to an asymmetric Heck reaction [12). The reaction between 2,3-dihydrofuran and 4-chlorophenyl triflate was carried out under the same conditions as those of original nonfluorous reaction by using FjjBlNAP in BTF or benzene to provide the corresponding product, 2-(4-chloro-phenyl)-2,3-dihydrofuran, in 59% chemical yield or in 90% ee and 92% ee, respectively (71% chemical yield and 91% ee in the original reaction in benzene [13]) [Eq. (3)]. 

Dihydrofuran (10.137) has also proved to be a popular substrate for the asymmetric Heck reaction. Hayashi has reported that using a Pd/BINAP catalyst not only is the initial addition enantioselective, but that the diastereomeric intermediates, i.e. of structure (10.119) preferentially give different regioisomeric products (10.138) and (10.139). This effect is similar to that of a kinetic resolution (see Section 4.1). ... 

Hennessy, A.J., Malone, Y.M. and Gurry, P.J. (1999) 2,2-Dimethyl-2,3-dihydrofuran, a new substrate for intermolecular asymmetric Heck reactions. Tetrahedron Lett., 40,9163-6. 

The catalytic asymmetric arylation (Heck reaction) of 2,3-dihydrofuran to give (/J)-2,3-di-hydro-2-phenylfuran which, upon Jones oxidation, yields (/ )- 2 (for assignment, see p 439)80. 

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