Miyaura boronic ester synthesis

An alternate strategy was utilized in the synthesis of a potential thyroid receptor ligand [30]. Electrophilic bromination was followed by the Miyaura boronic ester synthesis to yield 49 [31]. Suzuki coupling between 49 and 2-bromothiazole was then accomplished to provide 50, a precursor to the derivative 51. Unfortunately, the presence of the thiazole at C(3), in 51 resulted in a decrease in binding affinity and selectivity as compared to the lead compound. 

In a route towards new estrogens which bind to the /1-unit of the K+-channel located on the surface of the endothelium, L.F. Tietze et al. described the synthesis of a novel enantiopure B-Nor-steroid, applying multiple Pd-catalyzed transformations [141] (Scheme 38). A combination of a Suzuki-Miyaura and a Heck reaction using a 2-bromobenzylchloride derivative and a boronic ester, derived from the enantiopure Hajos-Wiechert ketone [142-... 

The synthesis of lapatinib involves a Suzuki-Miyaura coupling of a (5-formylfuran-2-yl)boronic derivative and an aryl iodide and was studied in detail by several teams. " In a recent patent,researchers from Zentiva noticed that in their own attempts to use commercial boronic acid, the excess of this reagent required for optimal conversions and purity was dependent on the source (a common issue with boronic acids, which are often contaminated with anhydrides and borinic acid). Thus, they turned to cyclic boronic esters as a more reliable intermediate, allowing correct control of the amount of boron reagent. Transposition of a process originally developed for the coupling of (5-formylfuran-2-yl)boronic acid was successful. The authors compared... 

Mctal-catalyzcd boiylaiion of alkanes and arenes for the synthesis of boronic esters (Ishiyama and Miyaura)... 

The same year, Gandon et al. reported the synthesis of fused arylboronic esters 36 via cobalt(0)-mediated cycloaddition of alkynylboronates 33 with diynes 35 (Scheme 1.11) [22], The boronate is first reacted with Co2(CO)g at room temperature for 4 h to generate the corresponding dicobaltatetrahedrane 34. The diyne is then added and the mixture is refluxed for 2 h. To show the utility of the products, one of them was treated with phenyl iodide under Pd catalysis to give 37. Complementary to these investigations, Ru-catalyzed [2 - - 2 - - 2] cycloaddition of tethered alkynyl-boronic esters with alkynes was reported [23]. In this case, the borylated arene could not be isolated but was converted directly in situ by Suzuki-Miyaura coupling. 

Williams has reported the synthesis of biaryl moiety of proteasome inhibitors TMC-95/A/B by Suzuki cross-coupling of boronic ester 68 with indolyl iodide 69 to give precursor 70 in 90% yield [49]. The boronic ester 68 was obtained from the tyrosine derivative 71 with i)is(pinacol)diborane (37), Pd(dppf)Cl2 and KOAc via the Miyaura protocol (Scheme 3.31). 

A novel macrocyclization procedure involving ttvo distinct cross-coupling manifolds in a domino fashion has been reported by Zhu for the synthesis of bipheno-mycin model 86 [56]. Thus, treatment oflinear feis-iodide with fois(pinacol)diborane (37) in the presence of Pd(dppf)2Cl2 under defined conditions affords the biphenyl macrocyclic compound 86 in 45% yield through a Miyaura aryl boronic ester formation followed by its intramolecular Suzuki cross-coupling. The diiodide containing a free phenol function (R=H) gave the macrocycle (R=H) in only 22-25% yield under these conditions (Scheme 3.37). 

For the synthesis of a cavitand functionalized with terpyridyl groups via rigid linkages, transition metal catalyzed cross-coupling reactions are especially well suited. Starting with the boronic acid ester 48 [65], attachment of the terpyridyl groups to the cavitand was realized by Suzuki-Miyaura reaction with the tetraiodo-cavitand 47 (Fig. 15). 

Suzuki-Miyaura coupling, involving the reaction of aryl boronic derivatives with aryl halides in the presence of a palladium catalyst, is a very powerful method for the preparation of biaryls. Solutions of aryl bromides or iodides supported on onium salts via an ester link in an RTIL lead to BTSILs that can be engaged in the Suzuki-Miyaura coupling reaction with aryl boronic derivatives. like the Heck reaction, this coupling is also sensitive to the variations in different parameters. The possibility to synthesize libraries of biarylic derivatives by parallel synthesis is illustrated by (Scheme 5.5-39) [51]. 

The synthesis of dictyodendrins A and F was realized through a sequential C—H functionahzation strategy inclusive of an initial C3 arylation, a site-selective double C—H alkylation with an aryldiazoacetate derivative and a subsequent Suzuki-Miyaura cross-coupHng with indole-3-boronic acid pinacol ester 107 (2015JAC644). A formal 67r-electrocyc-lization of the resultant tetrasubstituted pyrrole 108 fashioned the required pyrrolo-[2,3-c]carbazole core (109) which was further elaborated to the targets. 

The synthesis of dibenzoazepinones 29 from 2-(2-bromophenyl)acetic acid esters 27 and 2-aminophenyl boronates 28 was reported, involving one-pot Suzuki-Miyaura coupling and subsequent lactamization reactions (13TL2916). 

A dichromium derivative has been prepared from pinacol (dichloromethyl)-boronate (163), anhydrous chromous chloride, and lithium iodide in THF at 25 °C [90]. With various aldehydes, RCHO, this reagent adds to the carbonyl carbon to form trans-l-alkenylboronic esters, RCH=CH-B(02C2Me4). For most examples yields were 84-91%, E Z ratios >95 5. This reaction was used recently to convert aldehyde 162 into alkenylboronic ester 164, an intermediate used for a Suzuki-Miyaura coupling in the asymmetric total synthesis of quinine and quinidine (Scheme 8.39) [91]. In the modified procedure, the chromium reagent was generated from 163 in the presence of the aldehyde substrate. 

To conclude, we should mention the work similar, in essence, in which thienyl-boronic acids or pinacol esters react with 1,2-dichlorohexafluorocyclopentene via the Suzuki-Miyaura coupling [111]. A doubtless advantage of the method is its applicability to various substrates bearing reactive functionalities such as cyano and ester moieties, which cannot be compatible nnder the conventional diarylethene synthesis conditions using organolithium reagents. 

Scheme 4 shows the synthesis of poly(/7-arylenevinylene)-type (PAV-type) jT-stacked polymer by Heck-Mizoroki cross-coupling [24, 25]. The treatment of pseudo-/7ara-divinyl[2.2]paracyclophane 14 with diiodofluorene 15 using a Pd(OAc)2/P(o-Tol)3/NBu3 catalytic system afforded the corresponding stacked polymer 16 in 96 % isolated yield with M =5,200 [26]. Poly(/7-arylene)-type (PA-type) jc-stacked polymers were prepared by Suzuki-Miyaura cross-coupling [27, 28], and a representative example is shown in Scheme 5. The Pd(PPh3)4-catalyzed polymerization of monomer 9 with bis(boronic acid ester) monomer 17 afforded the polymer 18 in 89 % isolated yield (Mn=2,600) [29].

Firooznia has reported the synthesis of 4-substituted phenylalanine derivatives via cross-coupling of protected (4-pinacolylboron)phenylalanine derivatives such as 61 with aryl and alkenyl iodides, bromides and triflates [44]. They have further shown that BOC derivatives of (4-pinacolylboron)phenylalanine ethyl ester 61 or the corresponding boronic acids undergo Suzuki-Miyaura reactions with a number of aryl chlorides in the presence of PdCl2(PCy)3 or NiCl2(dppf), respectively providing diverse sets of 4-substituted phenylalanine derivatives of type 62 [45]. This strategy has also been used for the synthesis of enantiomerically enriched 4-substituted phenylalanine derivatives (Scheme 3.28) [46]. 

Synthesis of a series of novel functionalized achiral and chiral allyl boronates has been recently reported by Ramachandran via nucleophilic SNj -type addition of copper boronate species (generated from the boronates 37, 141, 142 under Miyaura conditions) [115,116] to various functionalized allyl acetates that tvere prepared either via vinylalumination or by Baylis-Hillman reaction with various aldehydes [117]. The resulting allylic boronates bearing an ester moiety (X=OR) were subsequently used for the synthesis of a-alkylidene-/3-substituted-y-butyrolactones by allylboration of aldehydes (Scheme 3.76). 

---