Boronic acids alkynes

Water-soluble palladium(O) complexes have also been used as homogeneous catalysts in aqueous-solution alkylation reactions. The particular complex that has been used is Pd(TPPMS>3. Aryl or heteroaromatic halides can be coupled with aryl or vinyl boronic acids, alkynes, alkenes, or dialkyl phosphites with this palladium(0) complex. This complex in aqueous solution can also be used for the coupling of alkynes with unprotected iodonucleotides, iodonucleosides, and iodoamino acids (133). 

The iodination reaction can also be conducted with iodine monochloride in the presence of sodium acetate (240) or iodine in the presence of water or methanolic sodium acetate (241). Under these mild conditions functionalized alkenes can be transformed into the corresponding iodides. AppHcation of B-alkyl-9-BBN derivatives in the chlorination and dark bromination reactions allows better utilization of alkyl groups (235,242). An indirect stereoselective procedure for the conversion of alkynes into (H)-1-ha1o-1-alkenes is based on the mercuration reaction of boronic acids followed by in situ bromination or iodination of the intermediate mercuric salts (243). 

Petasis reported an efficient addition of vinyl boronic acid to iminium salts.92 While no reaction was observed when acetonitrile was used as solvent, the reaction went smoothly in water to give allyl amines (Eq. 11.54). The reaction of the boron reagent with iminium ions generated from glyoxylic acid and amines affords novel a-amino acids (Eq. 11.55). Carboalumination of alkynes in the presence of catalytic Cp2ZrCl2 and H2O affords vinylalane intermediates, which serve as nucleophiles in the subsequent addition to enantiomerically enriched... 

Relevant complexes have been isolated and fully characterized (4-10, 13-lb). The resulting arylpalladium complex 8 is able to react with various compounds such as terminal alkenes, alkynes, aryl boronic acids or hydrogen-transfer agents to give an organic molecule and palladium(O) (3, 17, 18). 

Recently, Larock and coworkers used a domino Heck/Suzuki process for the synthesis of a multitude of tamoxifen analogues [48] (Scheme 6/1.20). In their approach, these authors used a three-component coupling reaction of readily available aryl iodides, internal alkynes and aryl boronic acids to give the expected tetrasubsti-tuted olefins in good yields. As an example, treatment of a mixture of phenyliodide, the alkyne 6/1-78 and phenylboronic acid with catalytic amounts of PdCl2(PhCN)2 gave 6/1-79 in 90% yield. In this process, substituted aryl iodides and heteroaromatic boronic acids may also be employed. It can be assumed that, after Pd°-cata-lyzed oxidative addition of the aryl iodide, a ds-carbopalladation of the internal alkyne takes place to form a vinylic palladium intermediate. This then reacts with the ate complex of the aryl boronic acid in a transmetalation, followed by a reductive elimination. 

Using Pd-mediated cross-coupling reactions, such as Suzuki, Heck, and Sonoga-shira- Hagihara reaction, researchers efficiently constructed a library of 151 coumarin derivatives from eight 3-bromocoumarins cross-coupled with ten aryl/heteroaryl boronic acids, ten alkenes, and ten alkynes (Fig. 4). 

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 addition of Rh-Csp a-bonds to enones is a well-studied process. Lee s reaction is predicated on the idea that rhodium-catalyzed conjugate addition of boronic acids to enones can be interrupted by 1,1-insertion into an alkyne. Thanks to the high reactivity of rhodium toward alkynes and the effects of tethering, a partly intramo-... 

An alternate strategy to access cyclopropanol derivatives from an acyclic precursor has been reported by Imai and coworkers (equation 79). Alkyne hydroboration followed by treatment of the resulting boronic acid with tetramethyltartramide produced the cyclopropanation precursor. A subsequent diastereofacial cyclopropanation afforded the... 

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). 

Nucleophiles other than hydride can be added to support-bound imines to yield amines. These include C,H-acidic compounds, alkynes, electron-rich heterocycles, organometallic compounds, boronic acids, and ketene acetals (Table 10.9). When basic reaction conditions are used, stoichiometric amounts of the imine must be prepared on the support (Entries 1-3, Table 10.9). Alternatively, if the carbon nucleophile is stable under acidic conditions, imines or iminium salts might be generated in situ, as, for instance, in the Mannich reaction. Few examples have been reported of Mannich reactions on insoluble supports, and most of these have been based on alkynes as C-nucleophiles. 

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 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). 

Jamison has reported the unprecedented nickel-catalyzed assembly of allylic amines 156 from three simple starting materials alkynes, imines, and trialkylbor-anes or boronic acids. The participation of boronic acids in this methodology greatly enhances its synthetic potential, owing to their greater availability (Scheme 8.68) [145]. An asymmetric version of the reaction has also been developed but gave only moderate enantiomeric excesses (33 to 42%). 

Although catalytic amounts of Ag20 have been found to promote the palladium-catalyzed coupling of aryl boronic acids and terminal alkynes, the authors in this case do not attribute the desired reactivity to the formation, and subsequent transmetalla-tion, of a silver acetylide. Rather, it is proposed that the Ag20 activates the alkynylpalladium complex to allow transmetallation from the boronic acid, and that any competing formation of the silver acetylide results in a homocoupling of the alkynes (Scheme 1.55).123... 

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... 

Alkenylboronic acids and esters have been prepared by thermal or catalyzed hydroboration of 1-alkynes with catecholborane (HBcat), pinacolborane (HBpin), or dihaloboranes 41-43, followed by hydrolysis to boronic acids or alcoholysis to boronic esters. A convenient alternative to improve chemo- and regioselectivity is the hydroboration of alkynes with dialkylboranes. For selective removal of dummy groups, the oxidation of two cyclohexyl groups was conduced by treatment of l-alkenyl(dicyclohexyl)borane intermediates with Me3N-0 (Equation (7)).116 The... 

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),... 

If 2,3-dibromo propene is used as an allylic substrate the substitution product 71 can be either isolated or, after addition of additives and adjustment of the reaction conditions, 71 can readily react in cross-coupling reactions with alkynes (Sonogashira coupling), stannanes (Stille coupling), or boronic acids and boronates (Suzuki coupling) to provide the sequential allylic substitution-cross-coupling products 72-78 in moderate to good yields (Scheme 23). 

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