Rhodium-catalyzed hydroborations

Ligand Effects in Rhodium-catalyzed Hydroboration of Vinylarenes 269... 

Mannig and Noth reported the first example of rhodium-catalyzed hydroboration to C=C bonds in 1985.4 Catecholborane reacts at room temperature with 5-hexene-2-one at the carbonyl double bond when the reaction was run in the presence of 5mol.% Wilkinson s catalyst [Rh(PPh3)3Cl], addition of the B—H bond across the C=C double bond was observed affording the anti-Markovnikoff ketone as the major product (Scheme 2). Other rhodium complexes showed good catalytic properties ([Rh(COD)Cl2]2, [ Rh(PPh3)2(C O )C 1], where... 

An extensive array of chiral phosphine ligands has been tested for the asymmetric rhodium-catalyzed hydroboration of aryl-substituted alkenes. It is well known that cationic Rh complexes bearing chelating phosphine ligands (e.g., dppf) result in Markovnikoff addition of HBcat to vinylarenes to afford branched boryl compounds. These can then be oxidized through to the corresponding chiral alcohol (11) (Equation (5)) ... 

Many metals including nickel,32,33 ruthenium,34 iridium,35 36 lanthanum,37,38 titanium,39 and zirconium40-42 have been employed in this transformation with varying degrees of success, but rhodium has remained the metal of choice for transition metal hydroboration. The mechanism of rhodium-catalyzed hydroboration (Scheme 4), is thought to depend on the nature of the substrate, the catalyst, the ligand used and the reaction conditions employed.43... 

Shortly after the key mechanistic papers on rhodium-catalyzed hydroboration, Marks reported a hydroboration reaction catalyzed by lanthanide complexes that proceeds by a completely different mechanism.63 Simple lanthanide salts such as Sml3 were also shown to catalyze the hydroboration of a range of olefins.64 The mechanism for this reaction was found to be complex and unknown. As in other reactions catalyzed by lanthanides, it is proposed that the entire catalytic cycle takes place without any changes in oxidation state on the central metal. 

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... 

The development of chiral catalysts for use in enantioselective rhodium-catalyzed hydroborations was pioneered by Burgess9, Suzuki,77 and Hayashi.78 The chiral diphosphine ligands employed in their preliminary investigations 23-26 (Figures 2(a) and 2(b)), had previously been successfully applied in other catalytic asymmetric transformations. 

As a greater understanding has emerged of the control factors at play in enantioselective rhodium-catalyzed hydroborations, an increased number of novel chiral diphosphine ligands have been reported in the chemical literature (Figure 3), the majority of these within the last five years. 

Although the vast majority of centrally chiral diphosphine ligands to be employed in enantioselective rhodium-catalyzed hydroborations possess -symmetry, there are a few examples of ( -symmetric diphosphine ligands. Buono prepared bis(aminophosphine) ligands 35-38,81 while Bianchini reported (R, i )-BDPBzP 39 (Figure 5).82... 

Micouin investigated rhodium-catalyzed hydroboration as a means of desymmetrizing meso hydrazines 59 in an important new application.36 Enantiomeric excess of up to 84% was obtained after screening diphosphines such as DIOP and BDPP (Scheme 9). Interestingly, they noted an unprecedented reversal of enantioselectivity by changing from rhodium to iridium. 

PHENAP 65 was prepared and resolved98 in a similar manner to QUINAP 60 and tested in asymmetric rhodium-catalyzed hydroboration-oxidations." Impressive enantioselectivities were obtained and the sterically demanding cyclic substrates were hydroborated with 64-84% ee. Compared to the corresponding results obtained with diphosphine ligands, it is clear that QUINAP 60, and structural relatives 61-64 and PHENAP 65, give superior results in the asymmetric rhodium-catalyzed hydroboration of several vinylarenes, and are essentially the only practical solution for / -substituted alkenes.100 The reasons for this are not well understood, but thought to be due to the particular... 

Among recent examples that highlight the synthetic utility of transition metal-catalyzed hydroborations are its direction toward a formal syntheses of the non-steroidal anti-inflammatory agents Ibuprofen 131 and Naproxen 13214 15 139 as well as the anti-depressant Sertraline 133 (Figure 14).140 In the majority of cases, rhodium-catalyzed hydroboration is utilized and the rhodium(i) source generally is Wilkinson s catalyst RhCl(PPh3)3. 

Grieco in the total synthesis of (—)-epothilone B 134 used a rhodium-catalyzed hydroboration as a key step in the synthesis of the macrocyclic ring (Figure 15).141 Completion of the synthesis of the C(3)-C(12) fragment was carried out using a rhodium-catalyzed hydroboration as the key step. 

Roush used a rhodium-catalyzed hydroboration to construct a component 136 of the natural product, (—)-bafilo-mycin A1 137 (Scheme 16).142 The hydroboration was carried out in 87% yield. 

In conclusion it is evident from the foregoing examples that transition metal-catalyzed hydroborations and hydroaluminations occupy an important role in organic synthesis. While rhodium-catalyzed hydroboration has been extensively developed, the hydroalumination is just starting to emerge as a useful reaction in organic synthesis. 

Scheme 4.S8. Zirconium- and rhodium-catalyzed hydroborations of alkenes and alkynes with pinacolborane.

The rhodium-catalyzed hydroboration has opened the way to cyclization reactions starting from dienes [92], For instance, rhodium-catalyzed hydroboration of the terminal alkenyl group of an os/Tunsaturated lactone followed by reaction with the PTOC-OMe chain transfer reagent afforded the bicyclic a-S-pyridyl lactone in 63% yield (Scheme 39). After oxidation of the sulfide with m-CPBA, thermal elimination of the sulfoxide afforded the corresponding a-methylene lactone in 65% yield. Interestingly, such bicyclic a-methylenelactones are substructures that can be found in many natural products such as mirabolide [93]. 

Fig. 2.2 Key features of the computational pathway for rhodium-catalyzed hydroboration, with energies in kcal/mol. Similar results were obtained for the related dioxaborolidine pathway. The isomeric intermediate C does not have access to a low energy H-migration pathway but rather eliminates B-H.

Fig. 2.4 A possible pathway for rhodium-catalyzed hydroboration by RhCI(PPh3)3, based on the mechanism of hydrogenation and the contributions of Evans and others [17], This takes into account the theoretical support for an associative pathway [13] and the observed irreversibility of the H-transfer step with styrenes.

Fig. 2.8 A d irect route to vinylboranes in rhodium-catalyzed hydroborations with phos-phine-free catalysts (including oxidative degradation of a rhodium phosphine). The key intermediate is a rhodium hydride, capable of reversible insertion into the alkene (step A), followed by addition of borane in step B. This leads to reductive elimination of RH in step C followed by boryl migration in step D. A further...

Tab. 2.1 Recent rhodium-catalyzed hydroborations with diphosphine ligands - work-up oxidation...

Terminal alkenes react almost instantaneously in rhodium-catalyzed hydroboration, whereas disubstituted alkenes require the use of excess reagent and increased amounts of catalyst (2-5%)362 Other alkenes are unreactive. High regioselectivities can be achieved 363,364... 

A multistep pathway analogous to the mechanism of alkene hydrogenation has been shown to be operative in the rhodium-catalyzed hydroboration of alkenes.363 Deuterium labeling studies furnished evidence that the reversibility of the elementary steps is strongly substrate-dependent. The key step is hydride rather than boron migration to the rhodium-bound alkene. 

The hydroboration of allylic amine or alcohol derivatives can be used for the preparation of alkylzinc reagents with excellent diastereoselectivity (Equation (34)). Rhodium-catalyzed hydroborations are also compatible... 

Scheme 1 A general proposed mechanism for the rhodium-catalyzed hydroboration of alkenes using HBcat...

An important aspect of the metal catalyzed hydroboration reaction is its ability to selectively reduce certain functionalities within a molecule. For instance, a key step in the synthesis of a tripeptide derivative containing the Phe-Arg hydroxyethy-lene dipeptide iosostere is the selective rhodium-catalyzed hydroboration of a lactone. The use of disiamylborane, 9-H-BBN, dicyclohexylborane, and (.9)-alpmeborane, however, gave only low to variable yields of the alcohol due to competitive reduction of the y-lactone to the hemiacetal (equation 8). In another example, hydroboration of the diene illustrated in equation (9) with HBcat and RhCl(PPh3)3 gave exclusive formation of the terminal alcohol derived from reaction of the less substituted alkene. Interestingly, uncatalyzed reactions failed to hydroborate this substrate selectively. ... 

The first facially selective hydroboration of a 5-methyhdene[2.2.1]bicychc intermediate has also recently been reported. The rhodium-catalyzed hydroboration of the methylidene group with HBcat proved superior to stoichiometric borane or dialkylborane reagents, in terms of higher diastereomeric excess and chemical yields (equation 15). For instance, while borane gave 89% of the desired 5-endo product along with 11% of the 5-exo product, the catalyzed variant with HBcat gave 95% for the desired 5-endo product when the reaction was run at room temperature. No improvement in diastereoselec-tivity was observed when reactions were run at lower temperatures. 

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