Alkenyl boronic acid

Palladium-catalyzed carbon-carbon bond forming reactions like the Suzuki reac-tion as well as the Heck reaction and the Stille reaction, have in recent years gained increased importance in synthetic organic chemistry. In case of the Suzuki reaction, an organoboron compound—usually a boronic acid—is reacted with an aryl (or alkenyl, or alkynyl) halide in the presence of a palladium catalyst. 

At about die same time, die application of the Suzuki coupling, the crosscoupling of boronic acids widi aryl-alkenyl halides in die presence of a base and a catalytic amount of palladium catalyst (Scheme 9.12),16 for step-growth polymerization also appeared. Schliiter et al. reported die synthesis of soluble poly(para-phenylene)s by using the Suzuki coupling condition in 1989 (Scheme 9.13).17 Because aryl-alkenyl boronic acids are readily available and moisture stable, the Suzuki coupling became one of die most commonly used mediods for die synthesis of a variety of polymers.18... 

Alkenylboronic acids, alkenyl boronate esters, and alkenylboranes can be coupled with alkenyl halides by palladium catalysts to give dienes.223... 

The same ligand allowed the cross-coupling of various boronic acids (aryl, alkenyl, alkyl) with alkyl bromides in the system (Pd(OAc)2/PMe Bu2, BuOK. amyl alcohol, r.t.).411... 

A rapid MW-assisted palladium-catalyzed coupling of heteroaryl and aryl boronic acids with iodo- and bromo-substituted benzoic acids, anchored on TentaGel has been achieved [174]. An environmentally friendly Suzuki cross-coupling reaction has been developed that uses polyethylene glycol (PEG) as the reaction medium and palladium chloride as a catalyst [175]. A solventless Suzuki coupling has also been reported on palladium-doped alumina in the presence of potassium fluoride as a base [176], This approach has been extended to Sonogashira coupling reaction wherein terminal alkynes couple readily with aryl or alkenyl iodides on palladium-doped alumina in the presence of triphenylphosphine and cuprous iodide (Scheme 6.52) [177]. 

The first example of a stable 1,1-bidentate Lewis acid based on boron and zirconium has been reported [35]. The synthesis of 22 is outlined in Scheme 7.12. Treatment of hex-l-yne with HBBr2 Me2S followed by conversion of the dibromoboronic ester to the corresponding alkenyl boronic acid and esterification with propane-1,3-diol provided the alkenyl boronic ester. Hydrozirconation of this compound with 3 equivalents of the Schwartz reagent, Cp2Zr(H)Cl [57], afforded the desired product 22 in 86% yield. 

The application of in situ-generated (alkoxy)palladium(II) species (Scheme 14.23) can be extended to reactions of a-carbonates with organoboron compounds. Crosscouplings of allenes 108 with aryl (or alkenyl) boron acids or their esters catalyzed by a palladium(O) complex afforded the 2-aryl(alkenyl)-l,3-butadienes 109 in excellent yields (Scheme 14.24) [53], The coupling reactions of 9-BBN-derived intermediates such as ester 111 can be accelerated by applying K3P04 as additive (Eq. 14.15). 

The palladium-catalyzed coupling of boronic acids with aryl and alkenyl halides, the Suzuki reaction, is one of the most efficient C-C cross-coupling processes used in reactions on polymeric supports. These coupling reactions requires only gentle heating to 60-80 °C and the boronic acids used are nontoxic and stable towards air and water. The mild reaction conditions have made this reaction a powerful and widely used tool in the organic synthesis. When the Suzuki reaction is transferred to a solid support, the boronic add can be immobilized or used as a liquid reactant Carboni and Carreaux recently reported the preparation of the macroporous support that can be employed to efficiently immobilize and transform functionalized arylboronic adds (Scheme 3.12) [107, 246, 247]. 

The transformation of lithio derivatives of dibenzothiophene into alkyl, alkenyl, hydroxyalkyl, formyl, acetyl, carboxylic acid, alkyl and arylsilyl, boronic acid, aryl and carbinol derivatives of dibenzothiophene is dealt with in the appropriate sections. In addition, the four mono-tritio derivatives of dibenzothiophene have been prepared from the corresponding lithio derivatives via hydrolysis with tritiated water (Section III, 0,2). ... 

In the same year, Hibino et al. reported a total synthesis of furostifoline (224) employing a new type of electrocyclic reaction (636). This cyclization proceeds through a 2-alkenyl-3-allenylindole intermediate, which is derived from 2-(fur-3-yl)-3-propargyUndole 1128. Compound 1128 was prepared starting from 2-chloroindole-3-carbaldehyde (891), furan-3-boronic acid (1124), and ethynylmagnesium bromide. 

A novel method for the convenient synthesis of alkenyl fluorides 15, as well as diflu-oromethyl-substituted alcohols 16 and amides 17, via electrophilic fluorination with one equivalent of F-Teda BF4 (6) of alkenyl boronic acids and trifluoroborates, has been reported.87 The alkenyl fluorides 15 are obtained as Z/E mixtures when the reaction is carried out with one equivalent of F-Teda BF4 in acetonitrile at room temperature. When the reaction is performed with two equivalents of F-Teda BF4 in water or a nitrile solvent the difluoromethyl-substituted alcohols 16 or amides 17, respectively, are obtained. 

Benzodioxaboroles (79) are easily hydrolyzed by water at room temperature. Attention has been paid to the parent 1,3,2-benzodioxaborole (79 R = H) as a hydroborat-ing agent of alkenes and alkynes to give, after hydrolysis, alkyl- and alkenyl-boronic acids. Compound (79 R = H) is oxidized by dry air at room temperature (75JA5249). 

Hayashi et al. and Miyaura et al. have reported that far less nucleophilic aryl- and alkenyl-boronic acids can react with a variety of enones in the presence of a BINAP-rhodium catalyst to give adducts with high enantiopurity in general (Scheme 8D.5) [13], The one pot procedure, involving the hydroboration of alkynes as the first step (R = alkenyl), was achieved in the presence of amines without affecting the enantioselectivity [13]. 

As noted for the Heck reaction, aryl, alkenyl, and alkynyl bromides, iodides, and triflates are best for the oxidative addition. However, aromatic, heteroaromatic, alkenyl, and even alkyl boronic acids and esters can be coupled effectively. The reaction appears almost oblivious to other functional groups present ... 

The ketone carbonyl of a series of isatins (63) undergoes enantioselective addition of aryl- and alkenyl-boronic acids, using a rhodium catalyst and a chiral phosphine.180... 

The use of alkenyl boronic acid derivatives 50, which are readily prepared via hydroboration or bromoboration of alkynes, affords the corresponding p,y-unsaturated amino acids (e.g. 52-57) in a geometrically pure form [34], A variety of amines 48, including primary and secondary amines, anilines, amino alcohols and hydroxylamines can effectively participate in this process, while the alkenyl boronic acid can contain alkyl, aryl or bromo-substituents. Although the alkenyl amino acid side chain is introduced through the boronic acid component, the use of more substituted a-keto acids 49 allows the simultaneous incorporation of an additional a-substituent (e.g. 57). 

Finn [66] has reported that when alkenyl boronic acids are used in this process, the aminomethylphenol intermediates can undergo a further transformation to generate 2Ff-chromenes 153 (Scheme 7.20). This process can be done efficiently with catalytic amounts of dibenzylamine or the corresponding polymer-supported amine 154 to afford a variety of substituted 2H-chromenes 155-159 in one step. 

Similarly, the reaction of alkenyl boronic acids with azomethines can be found. Indeed, the corresponding 3-CR was used by Petasis [33] for the enantioselective synthesis of a-amino acids starting from amines, a-keto acids and alkenyl boronic acids. 

The Suzuki Coupling, which is the palladium-catalysed cross coupling between organoboronic acid and halides. Recent catalyst and methods developments have broadened the possible applications enormously, so that the scope of the reaction partners is not restricted to aryls, but includes alkyls, alkenyls and alkynyls. Potassium trifluoroborates and organoboranes or boronate esters may be used in place of boronic acids. Some pseudohalides (for example triflates) may also be used as coupling partners. 

A diastereoselective Rh(I)-catalysed conjugate addition reaction of aryl- and alkenyl-boronic acids to unprotected 2-phenyl-4-hydroxycyclopentenone (207) has been investigated. The free OH group on the substrate was found to be responsible for the (g) stereochemistry, which is cis for arylboronic derivatives (208). In the case of the alkenylboronic compounds, the stereochemistry can be tuned to either a cis (with a base as additive) or trans addition (209) (with CsF as additive), without the need for protecting groups.249... 

Fig. 16.15. Stereoselective preparations of trans-alkenyl-boronic acid esters (B) and trans-alkenylboronic acids (C) and their stereoselective conversion into c/s-bromoalkenes and trans-iodoalkenes, respectively.

Fig. 16.16. Stereoselective preparations of cis-alkenyl-boronic acids and the corresponding diisopropyl ester starting with cis-bromoalkenes. The first step involves a Br/Li exchange to form the alkenyl-lithium compound B. This organolithium compound is subsequently transmetalated to give complex C by using B(0/Pr)3.

Fig. 16.19. Palladium-cata lyzed, stereoselective alkenylation of an arylboronic acid (preparation according to Figure 5.39) with a variety of iodoalkenes. The boronic acid is converted into the boronate anion A. The ion A reacts with the Pd(II) intermediate B via transmetalation subsequent reductive elimination leads to the coupling products.

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