Alkenyl boronates

The only preparative limitation to this method is the occasional coproduction of alkenyl-boronates that presumably arise via a-elimination pathways of the ate complex generated upon addition of the organometallic reagent to the a-haloalkylboronate4,29-30. This problem is illustrated in the synthesis of 5-(rm-butyldimethylsilyloxy)-2-pentenyl-substituted dioxaborolane30. 

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... 

The metal catalysed hydroboration and diboration of alkenes and alkynes (addition of H-B and B-B bonds, respectively) gives rise to alkyl- or alkenyl-boronate or diboronate esters, which are important intermediates for further catalytic transformations, or can be converted to useful organic compounds by established stoichiometric methodologies. The iyn-diboration of alkynes catalysed by Pt phosphine complexes is well-established [58]. However, in alkene diborations, challenging problems of chemo- and stereo-selectivity control stiU need to be solved, with the most successful current systems being based on Pt, Rh and An complexes [59-61]. There have been some recent advances in the area by using NHC complexes of Ir, Pd, Pt, Cu, Ag and Au as catalysts under mild conditions, which present important advantages in terms of activity and selectivity over the established catalysts. 

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

Stereo- and regioselective synthesis of trienes and tetraenes has been reported by palladium-catalysed coupling of (E)- or (Z)-l-alkenyl boronates with (E)- or (Z)-2-bromo-1-phenylthio-l-alkenes followed by treatment with a Grignard reagent in the presence of a nickel catalyst (equation 146)259. 

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). 

For both 1 and 2, the synthesis started with the alkenyl amide 3. Salen-mediated conjugate addition proceeded with remarkable induction, to give S in 92% as a mixture of diastereomers. Reduction and cyclization followed by deprotonation and kinetic quench delivered the enantiomerically-enriched cis dialkyl piperidine 6. Homologation of the two sidechains then gave the alkenyl boronic ester 8. 

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]. 

The major improvement compared to the Rh(I) catalysts was the ability of the Cu(I)/RB (OR )2 system to also carboxylate alkenyl-boronic esters in very good yield, under similar conditions. Interestingly, the system functioned better under ligandless conditions, producing the corresponding unsaturated carboxylic acids in good yields. 

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. 

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.

These boronic esters are easily hydrolyzed to give frara-alkenylboronic acids with complete retention of their stereochemistry (C in Figure 13.10). Alkenylboronic esters and alkenylboronic acids are organometallic compounds that can be alkenylated and arylated in Pd-catalyzed reactions (Section 13.3.2). Aside from this, the fram-alkenyl-boronic acid esters as well as the frara-alkenylboronic acids are valuable precursors of haloalkenes (Figure 3.10). 

A stereoselective synthesis of substituted pyrrolidines has been achieved by a sequential domino Michael addition and intramolecular carbozincation. The intermediate zinc-copper reagent obtained after cyclization can be trapped with an electrophile such as allyl bromide (Scheme 18).180 Addition of zincated hydrazones 52 on alkenyl boronates, followed by a trapping with an electrophile, provides adduct of type 53 with good yield and high diastereoselectivity (Scheme 19).181 By this addition/trapping sequence, several contiguous stereogenic centers are created in one step. 

Alkenyl boronic acids synthesized from internal alkynes fail to undergo the reaction with iodine and base. However, alkenylboronic acids and esters obtained from internal alkynes react with bromine in the presence of base to afford in excellent yields the corresponding alkenyl bromides (Eq. 112)174),... 

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,... 

Bromoboration of terminal alkynes 4 into the /J-bromo-l-alkenyl-boronic esters 5 [26], followed by a palladium-catalyzed displacement of the /J-halogen with organozinc reagents [27] is a known strategy for the preparation of metalated diene 6 (Scheme 3). An additional approach is the diboration of symmetrically disubstituted alkynes 7 with bis(pinacolato)diboron 8, followed... 

N-l-Substituted iodoimidazoles behave normally with arylboronic acids to give cross-coupled products <2005T6056>. N-l-Substituted-2-bromoimidazoles also coupled efficiently with aryl boronic acids and alkenyl boronic acids to give cross-coupled products in high yields (Scheme 95) <2004JOC8829>. 

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