Styrene, 4- hydroboration

Very recent investigations of styrene hydroboration with C2-symmetrical 1,2-diphosphines give promising regio- and stereoselectivities. As with the other ligands described above, the electronic properties of the phosphorus substituents prove paramount in determining the reactivity (Scheme 12). Hence, the combination of (li ,2i )-l,2-bis(diphenylphosphino)cyclohexane (19) with [Rh(COD)2]+... 

The differences in the steric effect between catecholborane and pinacolborane, and the valence effect between a cationic or neutral rhodium complex reverse the re-gioselechvity for fluoroalkenes (Scheme 1-4) [26]. The reaction affords one of two possible isomers with excellent regioselectivity by selecting borane and the catalyst appropriately, whereas the uncatalyzed reaction of 9-BBN or SiaiBH failed to yield the hydroboration products because of the low nucleophilicity of fluoroalkenes. The regiochemical preference is consistent with the selectivity that is observed in the hydroboration of styrene. Thus, the internal products are selectively obtained when using a cationic rhodium and small catecholborane while bulky pinacolborane yields terminal products in the presence of a neutral rhodium catalyst. 

Hydroboration of styrene derivatives has been extensively studied, and perhaps these are the best substrates to consider in a discussion of the efficiency and selectivity of the catalysts (Table 1-1). A neutral rhodium-phosphine complex... 

Hydroboration is highly regioselective and stereospecific. The boron becomes bonded primarily to the less-substituted carbon atom of the alkene. A combination of steric and electronic effects works to favor this orientation. Borane is an electrophilic reagent. The reaction with substituted styrenes exhibits a weakly negative p value (-0.5).156 Compared with bromination (p+ = -4.3),157 this is a small substituent effect, but it does favor addition of the electrophilic boron at the less-substituted end of the double bond. In contrast to the case of addition of protic acids to alkenes, it is the boron, not the hydrogen, that is the more electrophilic atom. This electronic effect is reinforced by steric factors. Hydroboration is usually done under conditions in which the borane eventually reacts with three alkene molecules to give a trialkylborane. The... 

Hydroborating agent 1-Hexene 2-Methyl-1 -butene 4-Methyl-2-pentene Styrene... 

Variation in catalyst and ligand can lead to changes in both regio- and enantio-selectivity. For example, the hydroboration of vinyl arenes such as styrene and 6-methoxy-2-vinylnaphthalene can be directed to the internal secondary borane by use of Rh(COD)2BF4 as a catalyst.166 These reactions are enantioselective in the presence of a chiral phosphorus ligand. 

The use of chiral ligands in catalysts can lead to enantioselective hydroboration. Rh-BINAP171 C and the related structure D172 have shown good stereoselectivity in the hydroboration of styrene and related compounds (see also Section 4.5.3). 

Attempts to utilize rhodium complexes for hydroboration of vinylarenes (Equation (2)) were somewhat complicated by discrepancies in the results from different research groups. Thus, it was found that [Rh(PPh3)3Cl] catalyzed the addition of HBcat to styrene to afford a quantitative yield of the branched product 15... 

Similarly, hydroboration of p-methoxystyrene with HBcat using zwitterionic [(P-P)Rh(//6-catBcat)] ((4), P-P = dppe, dippe) or [(dippe)Rh(r/3-2-IVIc-a 11 y 1)] (dippe= l,2-bis(diisopropylphosphine)ethane) gave 99% of the internal hydroboration product. Complications arose in studying reactions of hindered styrenes due to the appearance of not only the hydroboration products (A and B), but also the dehydrogenative borylation products C and D (Scheme 5).32 The ratio of products was found to be highly catalyst dependent (Table 2).33... 

Table 4 Enantioselectivities for [Rh(COD)2]+/L catalyzed asymmetric hydroboration of styrene.

The electron-poor biphenyl diphosphine (15) displays poorer regioselectivity for hydroboration of styrene (78% chemical yield) but higher enantioselectivity (78%).51 The [l,2-(diphenylphos-phino)ferrocenyl]ethyldicyclohexylphosphine (JOSIPHOS) ligand52 (16) in combination with... 

Chiral ruthenocenyl phosphine ligands offer no great advantages for hydroboration of styrene relative to the ferrocenyl analogues.56... 

In order to account for the high regioselectivities observed in the rhodium-catalyzed hydroboration of styrenes, Hayashi proposed a modified mechanism which proceeds through 73-benzyl-rhodium complex 22 as a key intermediate (Scheme 7). Reductive elimination from this 73-benzyl-rhodium complex 22 produces the secondary alkylborane regioselectively.12 A related 73-benzyl-palladium complex was recently isolated by Hartwig in studies of hydroamination.75... 

Of greater success were Knochel s -symmetric diphosphine ligands 28-34 (Figure 4) that proved highly successful when employed in the hydroboration of styrene and substituted styrenes.80 The corresponding 1-aryletha-nols was furnished with excellent regioselectivity (>99 1) and variable enantioselectivity after oxidation (Table 3). 

Table 2 Hydroboration of norbornene, indene, and styrene using catecholborane...

Table 3 Hydroboration of styrene and substituted styrene using ligands 32-34...

Application of these ligands to the hydroboration-oxidation of styrene proceeded with moderate yields and much lower enantioselectivities than for norbornene. The best result was with (R, R)-38, which afforded (A)-l-phenyletha-nol in 61% yield and 42% ee. However, Bianchini s (R, 7 )-BDPBzP 39 was even less efficient for this substrate, and gave both poor yields (29%) and poor enantioselectivities (26% ee) for the hydroboration of styrene at 0°C.84... 

While Josiphos 41 also possessed an element of atom-centered chirality in the side chain, Reetz reported a new class of ferrocene-derived diphosphines which had planar chirality only ligands 42 and 43, which have C2- and C -symmetry, respectively.87 Rhodium(i)-complexes of ligands (—)-42 and (—)-43 were used in situ as catalysts (0.75 mol%) for the hydroboration of styrene with catecholborane 1 for 12 h in toluene at — 50 °C. The rhodium/ i-symmetric (—)-43 catalyst system was the more enantioselective of the two - ( -l-phenylethanol was afforded with 52% and 77% ee with diphosphines (—)-42 and (—)-43, respectively. In both cases, the regioselectivity was excellent (>99 1). With the same reaction time but using DME as solvent at lower temperature (—60 °C), the rhodium complex of 43 afforded the alcohol product with an optimum 84% ee. 

Table 5 Hydroboration of styrene using chiral phosphite ligands 48-53... 

Ligand 73 was prepared directly from a single enantiomer of the corresponding naphthol of QUINAP 60, an early intermediate in the original synthesis, and both enantiomers of BINOL. Application in hydroboration found that, in practice, only one of the cationic rhodium complexes of the diastereomeric pair proved effective, (aA, A)-73. While (aA, A)-73 gave 68% ee for the hydroboration of styrene (70% yield), the diastereomer (aA, R)-73 afforded the product alcohol after oxidation with an attenuated 2% ee (55% yield) and the same trend was apparent in the hydroboration of electron-poor vinylarenes. Indeed, even with (aA, A)-73, the asymmetries induced were very modest (31-51% ee). The hydroboration pre-catalyst was examined in the presence of catecholborane 1 at low temperatures and binuclear reactive intermediates were identified. However, when similar experiments were conducted with QUINAP 60, no intermediates of the same structural type were found.100... 

The two-substituted-Quinazolinap-derived rhodium complexes proved extremely efficient catalysts for the hydro-boration-oxidation of vinylarenes (Table 6). For styrene derivatives, in most cases quantitative conversions were obtained after just 2 h at the relevant temperature (entries 1-6). Higher enantioselectivities were afforded with a 4-methoxy substituent (up to 95% ee, entry 3) compared to the 4-chloro or unsubstituted styrene analogs (entries 5 and 1), a trend also observed in hydroboration with rhodium complexes of QUINAP 60. This highlights that both the electronic nature of the substrate combined with the inherent steric properties of the catalyst are important for high asymmetric induction. It is noteworthy that in most cases, optimum enantioselectivities were afforded by the... 

Table 6 Hydroboration of substituted styrene using Quinazolinap ligands 66-71...

Rhodium complexes (lmol%) prepared in situ from [Rh(GOD)2]BF4 and the respective ligands 80-83 were employed in the enantioselective hydroboration-oxidation of styrene (Table 7).114-117... 

Table 7 Hydroboration of styrene using pyrazole containing ferrocenyl ligands 80-83...

Table 8 Hydroboration of styrene using ferrocene type ligands...

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