Boron-functionalized biphenyl

The cobalt-catalyzed Diels-Alder reaction of alkynylboron units could also be applied to the synthesis of boron-functionalized biphenyl derivatives such as 46. In... 

In a simple strategy to biaryl formation, Han et al.89 showed that silicon-directed ipso-substitution and concomitant cleavage from supports could be used for formation of functionalized biphenyls. For this they used a tethered silyl aryl bromide in a Suzuki cross-coupling reaction, followed by the ipso-substitution/cleavage step (Scheme 39). A variety of boronic acids were coupled in this manner. The only difficulty occurred with electron-deficient nitrophenylboronic acid where the desired product was formed under anhydrous conditions in only 33% yield (the remainder being starting material). Reversion to the more usual conditions of aqueous base-DME (i.e., those used by Frenette and Friesen)70 improved the yield to 82%. 

Further work has been reported on combinatorial approaches to the synthesis of phosphine derivatives of aminoacids. Various routes have been developed for the synthesis of boron-functional phosphines, e.g., (122) and (123). The search for ever-improved phosphine ligands for use in metal ion-catalysed reactions has led to the synthesis of a range of new chiral ligands, e.g., (124), various phenylnaphthyl-phosphines, e.g., (125) and (126), and other axially-chiral phosphinobiaryls, including (127) ° and a new PEG-supported bis(diphenylphosphino)biphenyl. ... 

The use of alkynyl pinacolboronic esters such as 17 afforded functionalized building blocks with high synthetic potential. The primary boron-functionalized dihydroaromatic intermediate could be used directly in a Suzuki cross-coupling reaction with 2,6-dimethoxyiodobenzene to afford the biphenyl derivative 18 in good yield, which was then converted into heterocycle 19 (Scheme 13.10) [10],... 

Later, Barrett created the term ROMPgel for linear polymers, which swell but do not dissolve in certain solvents because of solubility restrictions governed by the nature of the functional monomer used. Such ROMPgels were prepared with a variety of different functional groups including phosphines [3], allyl-boronates [25], a polymeric Tosmic reagent [26], naphthalenes, and biphenyls [27], alkylphosphonates [28], as well as anhydrides [29], some in a precipitation polymerization setup similar to the one described by our group. 

In 2012, Doucet s group [11a] reported the heteroarylation of 2-arylpyridine derivatives using heteroaryl dihalides (containing bromine and chlorine) - the bromine was selectively substituted (Figure 4.4). The reaction scope was demonstrated, the conditions were tolerant of a large diversity of functional groups. They also showed that the products could be successfully coupled with a number of boronic acids to give bi(biphenyl) products. Unfortunately, a sequential one-pot procedure was... 

The complexation of aldoses with cholesterol-derived boronic acids has been reviewed, and the changes in UV absorption and fluorescence intensity of a stilbene-type boronic acid on complexation with aldoses, especially D-fructose, have been studied with a view to their use in sugar-detection. Similar work has been carried out with diboronic acids derived from biphenyl and a -functionalized diaza-18-C-6 crown ether.A carbohydrate boronic acid derivative with liquid crystal properties referred to in Chapter 6, and further reports on boronate esters are noted in Chapter 17. 

The intramolecular diyne intermediate A formed in situ from alkynyl-boronate 2.144 and propargyl alcohol 2.145 forms metallocycle 2.146 with the catalyst [Cp RuCl (cod)]. The regioselective addition of the ruthenacycle 2.146 to the terminal alkyne 2.147 results in formation of arylboronate B. The latter without isolation undergoes further functionalization to form substituted biphenyl 2.148 in a satisfactory yield. 

A heavily functionalized atropisomeric biphenyl derivative (designed for use as liquid crystal dopant) has been recently synthesized, although in low yield, with Suzuki coupling as the key step [40], The coupling reaction is complicated by rapid hydrolytic deboronation of the sterically crowded electron-deficient boronate ester 55. Rigorously anhydrous conditions are required to avoid the deboronation step (Scheme 3.24). 

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). 

Evans has also developed an intramolecular version of the Cu(II)-assisted boronic acid O-arylation reaction and has applied it to the synthesis of macrocyclic biphenyl ether hydroxamic acid inhibitors of collagenase 1 and gelatinases A and B [65]. The reaction proceeds under sufficiently mild conditions to accommodate chemical functionalities commonly used in peptidomimetics synthesis (Scheme 3.44). 

---