Boronic transmetallation with

In recent years, a variety of aryl boronic acids are commercially available, albeit in some cases they may be expensive for large scale purposes. During our work in the mid-1990 s boronic acid (II) was not commercially available and so two different protocols were used to prepare this acid. The first approach involved the transmetallation with n-butyl lithium of aryl bromide (I) and trapping the lithio species generated with trialkyl borate followed by an acid quench. Aryl bromide (I) is easily prepared by reaction of o-bromobenzenesulfonyl chloride with 2-propanol in the presence of pyridine as a base. The second approach was a directed metallation of isopropyl ester of benzene sulfonic acid (VII), to generate the same lithio species and reaction with trialkyl borate. The sulfonyl ester is prepared by reaction of 2-propanol with benzenesulfonyl chloride. From a long-term strategy the latter approach is... 

Better results can be obtained by generating the boronate species with the aid of sodium methoxide. In this case, satisfactory transmetalation occurs on treatment with Cul. Thus, the functionalized copper reagent 55 can be alkynylated with 1-bromo-l-hexyne at —40 °C, furnishing the enyne 56 in 75% yield (Scheme 2.15) [32]. 

Aryltrimethyl stannanes are easily transformed into boronic acids by transmetalation with borane [106]. Thus, 1,4- and 1,3-Z>fy(trimethyl-stannanyl)benzenes as well as 2,5- and 2,6-Z /s(trimethylstannyl)pyridines synthesized by the SRN1 mechanism, react with borane in THF to give intermediates which on hydrolysis lead to benzene- and pyridinediboronic acids (Sch. 35) [107]. 

The hydroboration of allylic silanes proceeds with high diastereoselectivity as demonstrated by Fleming and Lawrence.87 It is difficult to use the newly formed carbon-boron bond for making new carbon-carbon bonds due to its moderate reactivity. However, the B/Zn exchange converts the unreactive carbon-boron bond to a reactive carbon-zinc bond, as in compound 24. A further transmetallation with the THF soluble salt CuCN-2LiCl provides copper reagents, which can be allylated, alkynylated, or acylated (Scheme 6). 

Alkenylzirconium compounds 34 obtained by the hydrometallation of alkynes were transformed to 1-alkenylboron compounds via transmetallation with B-halo-9-BBN or B-chlorocatecholborane62,63 (Scheme 5). Mercuration followed by transmetallation to BH3 was advantageous over the lithiation route in the synthesis of indole-3-boronic acid 35.64... 

The mechanism is very similar to that of the Stille coupling. Oxidative addition of the vinylic or aromatic halide to the palladium(O) complex generates a palladium(II) intermediate. This then undergoes a transmetallation with the alkenyl boronate, from which the product is expelled by reductive elimination, regenerating the palladium(O) catalyst. The important difference is the transmetallation step, which explains the need for an additional base, usually sodium or potassium ethoxide or hydroxide, in the Suzuki coupling. The base accelerates the transmetallation step leading to the borate directly presumably via a more nucleophilic ate complex,... 

Based upon this principle, aryl Pd species like 34 can also terminate in a transmetallation with boronic acids (i.e., in a Suzuki coupling) where the biphenyl 35 was obtained in 90% yield (Scheme 11) and the terphenyl derivative 36 was isolated in 93% yield (Scheme 12) [69]. 

Mechanism The reaction proceeds first by the oxidative addition of organohalide to the Pd(0) complex to give a palladium(II) intermediate as in the case of Stille coupling. The Pd(II) complex then undergoes transmetallation with the base-activated boronic acid to give complex B. This is followed by reductive elimination to form the active Pd(0) species, HX and the cross-coupled product (Scheme 5.17). 

The palladium-catalyzed coupling of boronic acids (as well as other boron derivatives) with aryl and vinyl halides and psendohalides is known as the Suzuki or Suzuki-Miyaura reaction. Because boron is nontoxic, this reaction has been used in pharmaceutical syntheses. In addition, hydroboration or borate substitution allows for the synthesis of virtually any desired coupling partner. For these reasons, as well as the high yields and functional group compatibility, the Suzuki reaction is the first reaction to consider for carrying out a cross coupling. Representative substrates and catalysts are shown in Scheme 17. The various bases are used to generate four-coordinate boron ate complexes that are more reactive in transmetalation. 

A final common arylation mechanism also involves C-H bond palladation with a Pd(II) catalyst, but then a transmetallation with an organometallic such as a boronic acid. Reductive elimination to form the desired product also releases Pd(0) and this species must be oxidized back to the active Pd(II) catalyst. A key aspect of this process is developing an oxidative system that does not result in homo-coupling of the aryl boronic acid (Scheme 9). 

These preliminary studies suggest a catalytic cycle initiated by electrophilic attack of palladium(II) on the indole, followed by transmetallation with a boronic acid and reductive elimination to produce the desired arylated products (Scheme 23). 

There are two reports of an alkyl to aryl rhodium migration process. The first example was reported in 2000 by Miura [75], It was discovered that, upon reaction of phenyl boronic acid with norbomene under rhodium-catalyzed conditions, a merry-go-around type sequential alkylation occurred up to four times on the aromatic ring, resulting in a 1,2,3,4-tetranorbomylated benzene as the final product (Scheme 16). Mechanistically, this reaction involves an alkyl to aryl migration of rhodium. Thus, aryl rhodium intermediate 29, generated via an initial transmetalation step,... 

Minor methods for the synthesis of boronic acids involve transmetallation with sihcon or mercury. ... 

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