Asymmetric hydroboration of styrene

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

Asymmetric hydroboration of styrenes employing diphosphine complexes provides a successful solution to the generation of chirality at a benTyhc site, a potentially important route to many bioactive molecules. Since substitution on the double bond leads to severe loss of enantioselectivity, the apphcations are necessarily hmited. It was adventitiously discovered that the P,N-ligand QUINAP [47], which is effective in asymmetric... 

Fig. 2.14 Carbon-carbon bond formation from the initital adduct of asymmetric hydroboration of styrene, (i) 2 mol% Rh(COD)2Bp4, L, 12 equiv. catecholborane, -66°C, DME (ii) pinalcol, 2 equiv., -66"C - RT, 12 h flash chromatography ...

Asymmetric hydroboration of styrenes with the bo-ranes derived from ephedrine and pseudoephedrine catalyzed by [Rh(nbd)(dppb)]OTf gives excellent regioselectiv-... 

P. Knochel and co-workers used diphosphines as ligands in the rhodium-catalyzed asymmetric hydroboration of styrene derivatives." The best results were obtained with the very electron rich diphosphane, and (S)-1-phenylethanol was obtained in 92% ee at -35 °C, with a regioselectivity greater than 99 1 (Markovnikoff product). A lower reaction temperature resulted in no reaction, while a higher temperature resulted in lower enantioselectivity and regioselectivity. The regioselectivity was excellent in all cases. Irrespective of the electronic nature of the substituents, their position and size had a profound effect on the enantioselectivity. 

Demay, S., Volant, F., Knochel, P. New C2-symmetrical 1,2-diphosphanes for the efficient rhodium-catalyzed asymmetric hydroboration of styrene derivatives. Angew. Chem., tnt. Ed. Engl. 2001,40,1235-1238. 

Table 2. Catalytic asymmetric hydroboration of styrene derivatives (16) with catecholborane (Scheme 3) ...

If catecholborane 8 is used for hydroboration, then conversion of the boronic ester product to a trialkylborane with a Grignard reagent or a dialkylzinc species is needed prior to amination. Thus, asymmetric hydroboration of styrene, followed by addition of methyl magnesium chloride then hydroxylamine-O-sulfonic acid gave... 

Hayashi, T. Matsumoto, Y. Ito, Y. Asymmetric Hydroboration of Styrenes Catalyzed by Cationic Chiral Phosphine-Rhodium (I) Complexes. Tetrahedron Asymmetry 1991,2,601-612. 

Hayashi, T. Matsumoto, Y Ito, Y. 1991. Asymmetric hydroboration of styrenes catalyzed by cationic chiral phosphine-rhodium(I) complexes. Tetrahedron Asymm. 2 601-612. 

Figure 7.4 Selected ligands for Rh(l)-catalyzed asymmetric hydroborations of styrene.

Asymmetric hydroboration of CtHsCH=CH2.2 The reaction of cate-cholborane with styrene provides, after oxidation, 2-phenylethanol. Hydroboration catalyzed by a cationic rhodium catalyst, [Rh(COD)2]+BF4 and dppb, provides 1-phenylethanol (99 1) in 86% yield. A catalytic asymmetric hydroboration is possible with BINAP. Use of (-)-BINAP as ligand and a temperature of -78° provides 1-phenylethanol in 96% ee (equation I). 

The reversal in the regioselectivity of the hydroboration of styrenes using a cationic rhodium complex (see Scheme 5.14), to provide the secondary (rather than primary) organoborane, allows the study of the asymmetric hydroboration of mono-Caryl) substituted alkenes (styrenes). A variety of chiral phosphine ligands can be used to good effect, a popular choice being (7 )-2,2 -bis(diphenylphosphino)-l, T-binaphthyl (BINAP). Just 0.02 molar equivalents of the rhodium catalyst and... 

In 1985, Manning and N6th first reported the hydroboration of alkenes catalyzed by Wilkinson s catalystJ Since this pioneering work, the development of transition-metal-catalyzed hydroboration has been investigated extensively. Burgess and Ohlmeyer demonstrated asymmetric catalysis with the use of BINAP and Diop-derived Rh-catalysts. Hayashi et al. later reported improvement of the enantioselectivity for the hydroboration of styrenes using Rh-BINAP complexes (up to 96% ee at -78 Other catalyst systems have also been shown to be effective... 

The asymmetric hydroboration of cis-polybutadiene had several butadiene-styrene copolymers failed the hydroxylated polymers and no optical activity. 

Complexes of cationic rhodium compounds with asymmetric phosphane ligands catalyze the hydroboration of prostereogenic alkenes with catecholborane (see Section D.2.5.2.1.4.). The product alcohols are of 7-96% cc (Table 3). Enantioselectivity is excellent for the hydroboration/oxidation of styrenes but low for stilbenes. The small number of examples studied to date precludes generalizations, however, compared to the uncatalyzed reaction, opposite regioselec-tivity is observed for the addition to styrenes. 

Asymmetric Hydroboration. Rhodium complexes are known to catalyze hydroboration of alkenes with unreactive borane derivatives, e.g. catecholborane and oxaborolidine. This reaction proceeds enantioselectively by use of BINAP as a ligand for neutral " or cationic rhodium complexes. Reaction of styrene with catecholborane followed by oxidation affords (R)-1-phenylethanol in 96% ee in the presence of (R)-BINAP and [Rh(cod)2]Bp4 (eq 5). ... 

Catalytic asymmetric hydroboration has been most extensively studied with styrene (4) as the substrate which produces 1-phenylethanol (6) after treatment of the hydroboration product, l-phenyl-l,3,2-benzodioxaborole (5), with alkaline hydrogen peroxide (Scheme 2). The regioselectivity favoring the branched isomer 5 over the linear isomer 5 is usually high when the reaction is carried out with rhodium complexes coordinated with chelating ligands such as bisphos-... 

The asymmetric synthesis of Gliflumide is still underway. We are near the conq)le-tion of the synthesis, and thus far we have definitively shown that the hydroboration protocol can be used with more conqilicated aryl systems than simple monosubsti-tuted styrenes. 

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