Phenylboronic acid, addition

Table 7.1 Rhodium-catalysed addition of phenylboronic acid to p-anisaldehyde...

The facile arylation of aldehydes with arylboronic acid has prompted the exploration of asymmetric versions of this reaction. However, this field has been scarcely explored and only few examples have been reported in the literature, with moderate results. The first diastereoselective example was described by Ftirstner and coworkers. By reacting the Gamer aldehyde 15 with phenylboronic acid under their set of experimental conditions (i.e. RhClj-SH O, IPr HCl) (Scheme 7.4) [21], the secondary alcohol was obtained in higher selectivity than that observed in the addition of phenylmagnesium bromide reported by Joullie (de = 94% versus 66%), with the anti isomer as the major compound [29]. 

Some other enantioselective approaches have been attempted, still with moderate enantioselectivities, by making use of in situ systems containing a chiral NHC precursor. Luo and co-workers reported on the use of the bidentate chiral imidazo-lium salt 16, derived from L-proUne, in combination with [RhCia-COCcod)], leading to an enantiometic excess of around 20% [30]. The use of chiral imidazolium salt 17 in combination with [RhCl(CH2=CHj)j]j by Aoyama afforded slightly better ee (Fig. 7.3) [31 ]. So far, Bohn and co-workers have obtained the best enantioselectivities (up to 38% ee) for the catalytic addition of phenylboronic acid to aromatic aldehydes by using planar chiral imidazolium salts 18, derived from paracyclophane, in combination with [Rh(OAc)2]2 [32]. 

Recently, Larock and coworkers used a domino Heck/Suzuki process for the synthesis of a multitude of tamoxifen analogues [48] (Scheme 6/1.20). In their approach, these authors used a three-component coupling reaction of readily available aryl iodides, internal alkynes and aryl boronic acids to give the expected tetrasubsti-tuted olefins in good yields. As an example, treatment of a mixture of phenyliodide, the alkyne 6/1-78 and phenylboronic acid with catalytic amounts of PdCl2(PhCN)2 gave 6/1-79 in 90% yield. In this process, substituted aryl iodides and heteroaromatic boronic acids may also be employed. It can be assumed that, after Pd°-cata-lyzed oxidative addition of the aryl iodide, a ds-carbopalladation of the internal alkyne takes place to form a vinylic palladium intermediate. This then reacts with the ate complex of the aryl boronic acid in a transmetalation, followed by a reductive elimination. 

Lamaty and coworkers described a straightforward combination of three Pd-cata-lyzed transformations first, an intermolecular nucleophilic substitution of an al-lylic bromide to form an aryl ether second, an intramolecular Heck-type transformation in which as the third reaction the intermediate palladium species is intercepted by a phenylboronic acid [124]. Thus, the reaction of a mixture of 2-iodophenol (6/1-253), methyl 2-bromomethylacrylate 6/1-254 and phenylboronic acid in the presence of catalytic amounts of Pd(OAc)2 led to 3,3-disubstituted 2,3-di-hydrobenzofuran 6/1-255 (Scheme 6/1.66). In addition to phenylboronic acid, several substituted boronic acids have also been used in this process. 

The group of Ley has reported on the use of palladium-doped perovskites as recyclable and reusable catalysts for Suzuki couplings [151]. Microwave-mediated cross-couplings of phenylboronic acid with aryl halides were achieved within 1 h by utilizing the supported catalyst (0.25 mol% palladium) in aqueous 2-propanol (Scheme 7.127). The addition of water was crucial as attempted transformations in non-aqueous mixtures did not proceed. 

Hayashi et al. proposed a catalytic cycle for the rhodium-catalyzed 1,4-addition of phenylboronic acid to 2-cyclo-hexenone (Scheme 28), which was confirmed by NMR spectroscopic studies.96 The reaction presumably involved three intermediates, phenylrhodium a, oxa-7r-allylrhodium b, and hydroxorhodium c complexes. Complex a reacted with 2-cyclohexenone to give b by insertion of the carbon-carbon double bond of enone into the phenyl-rhodium bond followed by isomerization into the thermodynamically more stable complex. Complex b was converted to c upon addition of water, liberating the phenylation product. Transmetallation of the phenyl group from phenylboronic acid to rhodium took place in the presence of triphenylphosphine to regenerate a. 

In 1997, Miyaura and co-workers reported the nonasymmetric version of 1,4-addition of aryl- and alkenylboronic acids to a,/ -unsaturated ketones using rhodium-phosphine complex as the catalyst.97 Later, Hayashi and Miyaura realized the asymmetric 1,4-addition with high catalytic activity and enantioselectivity.98 In the presence of ( y)-BINAP, the reaction of 2-cyclohexenone with 2.5 equiv. of phenylboronic acid gave (A)-3-phenylcyclohexanone with 97% ee (BINAP = 2,2 -bis (diphenylphosphino)-l,l -binaphthyl Scheme 29).99... 

Nitroalkenes are good candidates for the rhodium-catalyzed asymmetric 1,4-addition of organoboronic acids. Hayashi et al. reported that the reaction of 1-nitrocyclohexene with phenylboronic acid in the presence of rhodium/ -BINAP catalyst gave 99% ee of 2-phenyl-1-nitrocyclohexane (Scheme 38).117... 

Feringa and co-workers applied monophosphoramidite ligand 81 in the addition of phenylboronic acid to nitroalkene and got moderate enantioselectivity (Scheme 39).118... 

This catalytic reaction was believed to proceed analogously to those with phenylboronic acids (Scheme 49) 137 137a Transmetallation of the arylstannane with the cationic rhodium complex generated the rhodium aryl species a and trimethyltin tetrafluoroborate. Conjugate addition generated rhodium enolate b, which subsequently reacted with... 

On addition of fructose, the apparent p Ka value decreases, leading to the remaining four curves shown in Figure 3.21. The explanation for this observation lies in the fact that the fructose complex of 16 is a stronger acid than is 16 itself. This result was predicated on the work of Edwards, who reported the same trend in polyol complexes of phenylboronic acid in 1959.(23) As determined in the presence of a near-saturating amount of fructose (100 mM), the apparent pKa of the fructose-16 complex is 5.9. The... 

Organoboron reagents are particularly well suited for 1,4-additions of aryl and vinyl groups to enones. Hayashi et al. developed a highly enantioselective Rh(I)/ BINAP-catalyzed 1,4-addition of phenylboronic acid to cyclic and acyclic enones [24] (Scheme 7.5) and 1-alkenylphosphonates [25]. 

Scheme 7.5. Rhodium-catalyzed enantioselective 1,4-addition using phenylboronic acid.

Figure 3.19. Scope of Rh/42-catalyzed asymmetric 1,4-addition of phenylboronic acid to a,P-enones.

Scheme 3.1 Rhodium-catalyzed conjugate addition of phenylboronic acid to a,/ -unsaturated ketones [5].

Hayashi and co-workers established the catalytic cycle of the asymmetric conjugate addition in 2002 [16]. An example is outlined in Scheme 3.4 for the reaction of phenylboronic acid 2m with 2-cyclohexenone la. The reaction has three main intermediates hydroxo-rhodium (A), phenylrhodium (B), and oxa- j-allylrhodium (C) complexes. They are related in the catalytic cycle by (1) transmetallation of a phenyl group from boron to hydroxo-... 

Hayashi proved the validity of this catalytic cycle by the observation of aU three intermediates and their respective transformations using NMR experiments (Scheme 3.5) [16]. Transmetallation of a phenyl group from boron to rhodium takes place by addi-hon of phenylboronic acid 2 m to hydroxo-rhodium complex 16 in the presence of tri-phenylphosphine to generate the phenylrhodium complex 17. The reaction of 17 with 2-cyclohexenone la gives oxa- j-allylrhodium 18, which is converted immediately into hydroxo-rhodium complex 16 upon addition of water, liberating the phenylation product 3 am. In this NMR study, triphenylphosphine was used to stabilize the phenylrho-dium(I) complex. In the absence of triphenylphosphine, the characterization of the phenyl-rhodium species was unsuccessful. 

The rhodium-catalyzed asymmetric conjugate addition is applicable to a,yS-unsaturated esters (Scheme 3.8). Hayashi reported [20] that the reachon of 5,6-dihydro-2H-pyran-2-one 19a with phenylboronic acid gave a 94% yield of phenylated lactone (S)-20am with 98% enanhomeric excess. For the linear enoates, organoboronic acids did not give... 

An interesting asymmetric transformation is the asymmetric conjugate addition to a-acetamidoacryhc ester 30 giving phenylalanine derivative 31, which has been reported by Reetz (Scheme 3.10) [10]. The addition of phenylboronic acid 2m in the presence of a rhodium complex of l,T-binaphthol-based diphosphinite ligand 32 gave a quantitative yield of 31 with up to 11% enantiomeric excess. In this asymmetric reaction the stereochemical outcome is determined at the hydrolysis step of an oxa-7r-aUylrhodium intermediate, not at the insertion step (compare Scheme 3.7). 

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