Borylation regioselectivity

In 2011, Hartwig and coworkers reported the total synthesis of taiwaniaquinol B (55, Scheme 11.9), a member of a family of diterpenoids that are derived from the abietane skeleton [36]. A key aspect of the Hartwig synthesis of taiwaniaquinol B was the use of the iridium-catalyzed borylation reaction to accomplish the C(5) functionalization of resorcinol derivative 53. This regioselectivity for the overall bromination is complementary to that which would be obtained using a standard electrophilic aromatic substitution (EAS) reaction. In the transformation of 53 to 54, a sterically controlled borylation was first accomplished, which was then followed by treatment of the boronic ester intermediate with cupric bromide to... 

The regioselective borylation of alkanes can be achieved either catalytically or stoichiometrically using a host of metal complexes such as rhenium analogs. Such processes can be photochemically or thermally induced (Equation (19)).30 30a 30c... 

Remarkable carbon-boron bond-forming reactions are catalyzed by iridium complexes and proceed at room temperature with excellent regioselectivity, governed by steric factors. Heteroarenes are borylated in the 2-position and this reaction is generally tolerant of halide substituents on the arene (Equations (87) and (88)). 

In relation to the mechanistic proposal, an interesting reactivity of (boryl)(silyl)platinum(n) complex has been reported.223 The complex is prepared by the reaction of silylborane with Pt(cod)2 complex via oxidative addition (Scheme 46). The (boryl)(silyl)platinum complex undergoes insertion of alkynes at the B-Pt bond to give (/3-borylalkenyl)(silyl)platinum(n) complex in high yield. Importantly, the insertion takes place regioselectively, with Pt-G bond formation at the internal. -carbon atom. This result may indicate that the boron-transition metal bond is more prone to undergo insertion of unsaturated molecules. 

Addition of silylpinacolborane to alkenes has been achieved with platinum catalysts (Equation (83)).225 The reaction proceeds regioselectively to provide products in which the silyl groups are attached to the terminal carbon atoms contrary to the silaboration of alkynes. Although no regioisomers are detected, 1-boryl-l-silylalkenes are formed as major byproducts. 

In the reaction of an unsymmetrical diyne with 9, the boryl group is introduced regioselectively to the terminal acetylenic bond (Equation (100)). 

An enyne undergoes the stannaborative cyclization with 9 in a completely regioselective fashion (Equation (101)). The boryl group is introduced exclusively to the acetylenic bond to give an isomerically pure product. These results obtained with the unsymmetrical substrates suggest that the more reactive unsaturated bond initially inserts into the Pd-B bond. 

Stereoselective 1,4-addition of the tin-boron bond to 1,3-diene occurs in the presence of a palladium catalyst, which is prepared in situ from Pd(dba)2 and ETPO, at 80 °C in THF to give (Z)-l-boryl-4-stannyl-2-butenes (Equation (102)).249 For unsymmetrical 1,3-diene like isoprene, highly regioselective 1,4-stannaboration is observed. 

Diastereoselective aldol reactions The boryl enolates of chiral crotonate imides (1) and (2) react with aldehydes to form adducts (3) and (4), respectively, with high diastereoselectivity and complete a-regioselectivity. The method of choice for reductive cleavage of the adducts is formulated for 3 hydrolysis can also be effected with LiOH and H202. 

Silaboration of 3-substituted 1,2-dienes takes place smoothly at the internal double bond in the presence of the catalytic Pd(acac)2-2,6-xylyl isocyanide complex and the boryl group is regioselectively introduced to the central carbon atom of an allene (Scheme 16.55) [59, 60]. The same regioselectivity is observed with the catalytic system Pd2(dba)3-P(OCH2)3CEt [59]. 

Subsequent reports showed that a wide range of arene substrates could be borylated, with regioselectivity predominantly dictated by steric factors [77]. In the case of monosubstituted arenes, borylation generally occurs predominantly at the meta and para positions, with a near-statistical ratio while substitution at the ortho position is minor (Scheme 4). In the case of 1,3-disubstituted arenes, borylation occurs exclusively at 5-position. The selectivity was reversed in favor of the ortho position in the case of diethylbenzamide, presumably due to chelation [77]. 

The [Ir(OMe)(COD)]2/dtbpy catalytic system borylates indole selectively at the 2-position (Scheme 6). Smith and coworkers reported that borylation of N-unprotected 2-substituted indoles exclusively occurs at 7-position (Scheme 6) [85, 86]. It has been suggested that nitrogen interaction with the iridium center or possibly the empty p-orbital of boron in a boryl ligand induces the observed regioselectivity. Borylation of other heteroarenes have been reported using the same or similar Ir(I) and bipyridine combination [85, 87-90]. 

In the borylation of nonheteroaromatic rings, sterics are generally the most important factor influencing regioselectivity so that boronate is generally introduced at the sterically less hindered sites (e.g., meta or para in monosubstituted... 

Alkylidene borane 360 undergoes reaction with BH3-THF 361 to yield a dimerized cycloaddition product 362. BH3 hydroborates the B—C bond in two molecules of methylidene borane 360. The regioselectivity of hydroboration is governed by the electronic factors which facilitate the attack of boron (from BH3) on the two terminal carbon atoms, thus generating the B-C-B-C-B chain. The final product is obtained by the binding of two boryl ends via two B-H-B three-center, two-electron bridged bonds (Equation 20) <2004ZFA508>. 

Most current regioselective, catalytic functionalization of saturated C-H bonds [1-5] occurs by directed processes [6-13]. In these processes the catalyst or reagent docks at a functional group or reacts at C-H bonds that are located a to a heteroat-om, because these bonds are weaker than more distal ones [14]. Borylation of methyl C-H bonds complements the directed chemistry because it occurs at unactivated C-H bonds with regioselectivity that is independent of the position of the functional group in the reagent [15]. 

An iridium(l) complex, generated from l/2[Ir(OMe)(COD)]2 and 4,4 -di-/-butyl-2,2 -bipyridine (dtbpy), catalyzed the direct borylation of 2-substituted pyrroles in stoichiometric amounts relative to 2,2 -bi-l,3,2-dioxaborolane 785 in hexane at room temperature (Equation 188) <2003ASC1103>. The pyrrolylborates 786 from regioselective C-H activation at the 5-position were formed in high yields. Similar borylation of unsubstituted pyrrole with an equimolar amount of borolane 785 regioselectively provided 2,5-bis(boryl)pyrrole 787 (Equation 189). 

A highly regioselective borylation of arenes and heteroarenes (such as benzo[ ]furan 82) was achieved by the iridium-catalyzed C-H activation reaction, as shown in Equation (94) <2003CC2924>. 

Initial reports on the borylation of alkanes using isolated transition-metal-boryl complexes date back to 1995, when Hartwig showed that Cp Re(CO)2(Bpin)2 converts pentane to 1-borylpentane with high regioselectivity. " The catalytic C-H borylation of alkanes with Cp Re(CO)3 using photochemical activation was demonstrated soon thereafter (equation 25). Also, an efficient thermal process that involves the use of rhodium catalysts has since been developed (equation 26). It is interesting to note that this methodology is not restricted to small molecules, but has recently been exploited for the direct side-chain functionalization of polyolefins. ... 

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