Stannanes boron halides

The Stille Coupling is a versatile C-C bond forming reaction between stannanes and halides or pseudohalides, with very few limitations on the R-groups. Well-elaborated methods allow the preparation of differen, products from all of the combinations of halides and stannanes depicted below. The main drawback is the toxicity of the tin compounds used, and their low polarity, which makes them poorly soluble in water. Stannanes are stable, but boronic acids and their derivatives undergo much the same chemistry in what is known as the Suzuki Coupling. Improvements in the Suzuki Coupling may soon lead to the same versatility without the drawbacks of using tin compounds. 

Reactions of organometallic nucleophiles are reviewed mainly under Reactivity of Substituents Metals and Metalloids - this is a change from the Handbook-II policy of considering these under the reactions of Reactivity of Substituents Halides. Transition metal-catalyzed reactions of halides are considered partly under Reactivity of Substituents Halides and partly in the metalloids sections. Transition metal-catalyzed reactions of stannanes, boronic acids, etc., are considered under Reactivity of Substituents Metals and Metalloids. These areas represent the largest proportion of the additional new material since Handbook-II and are certainly the most important. 

One of the earliest methods for preparing aromatic boronic acids involved the reaction between diaryl mercury compounds and boron trichloride [198]. As organomer-curial compounds are to be avoided for safety and environmental reasons, this old method has remained unpopular. In this respect, trialkylaryl silanes and stannanes are more suitable and both can be transmetallated efficiently with a hard boron halide such as boron tribromide [199]. The apparent thermodynamic drive for this reaction is the higher stability of B-C and Si(Sn)-Br bonds of product compared to the respective B-Br and Si(Sn)-C bonds of substrates. Using this method, relatively simple arylboronic acids can be made following an aqueous acidic workup to hydrolyze the arylboron dibromide product [193]. For example, some boronic acids were synthesized more conveniently from the trimethylsilyl derivative than by a standard ortho-metallation procedure (entry 11, Table 1.3). 

Vinylation can also be done by Pd-catalysed cross-coupling in which one component is used as a halide or triflate and the other as a stannane (Stille reaction) or boronic acid (Suzuki reaction). Entry 9, Table 11.3, is an example of the use of a vinylstannane with a haloindole. lndole-3-boronic acids, which can be prepared by mcrcuration/boration, undergo coupling with vinyl triflates (Entry 10). 

The Suzuki coupling of arylboronic acids and aryl halides has proven to be a useful method for preparing C-aryl indoles. The indole can be used either as the halide component or as the boronic acid. 6-Bromo and 7-bromoindolc were coupled with arylboronic acids using Pd(PPh3)4[5]. No protection of the indole NH was necessary. 4-Thallated indoles couple with aryl and vinyl boronic acides in the presence of Pd(OAc)j[6]. Stille coupling between an aryl stannane and a haloindole is another option (Entry 5, Table 14.3). 

Allenyllithium reagents are commonly prepared through lithiation of propargylic halides or by deprotonation of alkynes or certain allenes (Eq. 9.1). Lithiated allenes often serve as precursors to stable allenylmetal compounds such as stannanes or silanes. They can also be employed for the in situ synthesis of allenylzinc, -titanium and -boronate compounds, which can be further transformed to substitution products not accessible from their allenyllithio precursors. 

Pyrrolyl- and indolyl-stannanes and -boronic acids, which can be prepared from the corresponding organolithium derivatives, have received increasing use in palladium-catalyzed coupling reactions with aryl halides (Scheme 82) (91S613,92JOC1653). 

Boranes and, to a lesser extent, boronic acids can undergo slow hydrolysis (protode-boration) in the presence of protic solvents. This unwanted reaction can become predominant if a cross-coupling reaction only proceeds slowly (e.g. with electron-rich, sterically demanding, or unreactive halides Scheme 8.20 see also Scheme 8.14) or if the boron derivative is particularly sensitive, for example 2-formylphenylboronic acid. In such instances the reaction should be performed under anhydrous conditions in an aprotic solvent with a boronic acid ester [151] or a stannane. 

This aUows the cross-coupling of an aryUialide (2) with an aryltrialkyl stannane in presence of a boronic ester. The latter remains unreactive because it would need to be hydrolyzed to a boronate to be suited for Pd-mediated couplings. Progression in a couphng cycle would further require OH , CO , or F , not present under the used StiUe couphng conditions [178,179]. The Stille conditions proved very useful for affording many aryl-aryl [1, 4, 180, 181, 182], vinyl-aryl [9, 161, 183, 184] and also aUcyl-aryl [185] compounds bearing hydrolytically labile moieties. The commonly used reactivities of aryl or vinyl halide components are like those in the... 

Some authors have described the generation of boronates and stannanes bound to a support starting from the corresponding aryl haHdes [372, 6]. Boranes, boronic esters, and stannanes can furthermore be readily obtained from vinyl halides or from alkenes or alkynes by means of hydroboration or hydrostannylation (see Section 4.2). Boronates and silanes or stannanes can act as carbanion equivalents. Thus, support-bound boronates can release aryl alkenyl groups upon transmetala-tion to Rh. The intermediately formed Rh species can act as nucleophiles, and react with aldehydes to give alcohols (618) or can perform Michael additions (621, 622) [437, 438, 439] (Scheme 129) (see also Sections 4.7.15 and 4.2). 

Another principal method is the fluorovinylation of suitable precursors by transition metal-catalyzed carbon-carbon coupling reactions [13]. Activated fluorovinyl species can be conveniently generated in situ from commonly used hydrofluorocarbons, for example HFC-134a [14] (Scheme 2.192). Fluorinated vinyl zinc halides are often used for the coupling reactions, but other activated species, for example stannanes [15] or boronates [16], have also been applied successfully. 

The palladium-catalysed reactions with alkenyl, aryl, and heteroaryl halides or triflates as one partner ( electrophilic ) and alkenes (Heck), aryl or vinyl stannanes (Stille) or aryl, vinyl and even alkyl boronic acids (Suzuki) as the other ( nucleophilic ) partner provide a synthetic method of astonishing power and versatility. These reactions are only just starting to be explored and great things are expected of them. 

Several groups have reported procedures for palladium-mediated cross-coupling of indoles. This can involve the indole reacting as the nucleophilic (eg. stannane, zinc or boronic acid derivatives) or electrophilic (halide or triflate) component. The variety of such procedures that are now available indicates that Pd-catalyzed cross-coupling is the most versatile method for synthesis of many aryl and vinyl indoles. 

The most important palladium-catalyzed processes include Heck vinylation of halides and sulfonates and various cross-coupling reactions in which a nucleophilic intermediate (stannane, organo-zinc halide or boronic acid) is coupled with an electrophile (halide or sulfonate). These coupling reactions are usually restricted to arylation and vinylation because of the tendency of alkylpalladium species to undergo elimination. The pyrrole and indole rings can participate in cross-coupling as either the nucleophilic or electrophilic component. 

Readily available functionalized aryl siloxanes are also viable cross-coupling partners for Pd(dba)2-catalyzed allylic arylations. A mixture of 5% Pd(dba)2, allylic halide, and in situ-generated aryl zinc reagent produces allylated arenes in high yield. Aryl boronic acids have been converted to allylated arenes as well. Diastereoselective intramolecular Stille-type coupling of two allylic moieties (aUylic acetate and allylic stannane) has been performed in high yield to produce the key intermediate in the synthesis of racemic 10-ep/-elemol (eq 19). ... 

B.ii.b. Termination by Boronates (Heck-Suzuki Cascade), Stannanes (Heck—Stille Cascade), or Cyanide Ion. The Heck reaction of aryl or alkenyl halides with norbomene can be terminated by coupling with either a boronate (Scheme 5, Eq. or an alkenylstannane (Scheme 5, Eq. 2) to stereoselectively formed vicinal biscoupling products with formation of two new C,C bonds. 

Coupling of organometallic reagents with halides in a carbon monoxide atmosphere leads to ketones by incorporation of a carbonylation step. These reactions involved a migration of one of the organic subsituents to the carbonyl carbon, followed by reductive elimination. These reactions can be carried out with stannanes " or boronic acidsas the nucleophilic component. 

---