Copper® -catalyzed borylations

In our previous Feature article [14], we discussed reaction mechanisms for various copper-catalyzed borylation processes and demonstrated that boryl ligands display nucleophilic behavior, in spite the presence of an empty p orbital on the boron... 

Copper-catalyzed Boryl Substitution of Allylic and Propar-gylic Carbonates. 

The addition of B pin to activated alkenes is an efficient way to generate alkylboronates. One version of this reaction entailed the use of a platinum complex to catalyze the addition, which generated remarkably high yields of the boronates when heated (Scheme 6.6) [12, 13]. While there was some substrate specificity, this was an effective approach to the synthesis of alkylboronate compounds from Michael acceptors. It should be noted that a chiral imidazolinium salt catalyzed the enantioselective borylation of acyclic enones with excellent selectivity (up to er=98 2 [ 14]). The copper-catalyzed borylation of cyclopropenes has also been reported using bisphosphine as the chiral ligand (Schanes 6.7 and 6.8) [15,16] in... 

SCHEME 6.4 Copper-catalyzed borylation of alkyl halides [4]. 

SCHEME 6.7 Copper-catalyzed borylation of functionalized cyclopropenes [15]. 

The expansion of this chemistry came by the work ofYun, since the copper borylation of a,P-unsaturated carbonyl compounds could be achieved by the activation of B2pin2 with CuCl in the presence of base and MeOH to favor the tr-bond metathesis. Remarkably, the use of chiral diphosphines to modify the Cu(I) salt was the key to dehver the Bpin moiety with asymmetric induction. A more detailed mechanism for the borylation of a,P-unsaturated carbonyl compounds was described by Lin with the aid of DFT calculations. The tr-bond metathesis step has also been elucidated, experimentally and theoretically, in the copper-catalyzed borylation of aryl hahdes with B2PUI2 by Marder and Kleeberg. 

Kleeberg C, Dang L, Lin Z, Marder TB. A facile route to aryl boronates room-temperature, copper-catalyzed borylation of aryl halides with alkoxy diboron reagents. Angew Chem Int Ed Engl. 2009 48 5350-5354. 

Ito, Kawakami and Sawamura recently described the borylation of al-lylic carbonates by B2pin2, catalyzed by bis(phosphine)copper(I) alkox-ides. It was proposed that bis(phosphine)copper(I) boryl species formed by alkoxide/boryl a-bond metathesis are key intermediates in the catalytic cycle [231]. Making use of related N-heterocyclic carbene stabilized precursors, Sadighi and co-workers have very recently isolated the thermally labile copper boryl complex (IPr)CuBpin (11.1) together with the products of oxygen atom, styrene and aldehyde insertion into the Cu-B bond (11.2-11.5 Scheme 24) [232,233,237]. The structure of 11.1 in the solid state reveals an approximately linear Cu(I) coordination geometry [ZB-Cu-C 168.1(2)°] and a Cu-B distance [2.002(3) A] which is somewhat shorter than the sum of the expected covalent radii [2.05 A] [106]. Yet further evidence for the... 

Tzschucke CC, Murphy JM, Hartwig JF (2007) Arenes to anilines and aryl ethers by sequential iridium-catalyzed borylation and copper-catalyzed coupling. Org Lett 9 761... 

Zhao H, Lin Z, Marder TB (2006) Density functional theory studies on the mechanism of the reduction of CO2 to CO catalyzed by copper(I) boryl complexes. J Am Chem Soc 128 15637... 

In 2010, McQuade and coworkers described the application of complex 98 in the enantioselective conjugate borylation of acyclic a,p-unsaturated esters (Scheme 3.62) [91]. The copper(I) complex 98 exhibited excellent reactivities (88-95% yields) and enantioselectivities (82-96% ee) for p-borylation of a variety of aliphatic and aromatic a,p-unsaturated esters by using 1 mol% of 98. As typical in NHC-Cu(I)-catalyzed borylation reaction, methanol was a necessary additive in this transformation. The system was highly reactive and catalyst loadings... 

The Ir catalyst [Ir(COD)OMe]2 was successfully exploited for the borylation of arenes under microwave conditions, this was then followed by the in situ copper-catalyzed sulfenylation of the intermediate aryl boronate to the aryl thioether product using an arylthiol, with microwave conditions [118]. 

Shen in 2012 reported an Ir/Cu synergistic catalytic C—H bond activation for the one-pot trifluoromethylation reaction (Scheme 9.19). This catalytic process involves sequential iridium-catalyzed C—activation borylation and copper-catalyzed trifluoromethylation of arenes with a variety of functional groups. This tandem procedure was successfully applied to the 2,6-disubstituted pyridine, benzofuran, benzothiazole, indole, and substituted quinoline systems. 

Scheme 6 NHC-copper(I)-catalyzed borylation of a,p-imsaturated amides by Hong...

Desymmetrization of Prochiral Compounds by Copper(I)-Catalyzed Borylation or Silylation... 

Copper(II)-catalyzed Boryl Addition to Allylic Carbonates. The conversion of allylic carbonates to chiral a-substituted allylboronates was also investigated by Hoveyda, who was able to accon ilish this transformation with a Cu(II)-NHC complex. This reaction proceeds in a vinylogous fashion to Sawamura s, but under these conditions, (E)- and (Z)-allylic carbonates undergo substitution to produce opposite enantiomers of product with similar yields and selectivity. This methodology is also tolerant of substitution at the a- or -position and is effective for di-or trisubstituted alkyl (linear or branched) or aryl alkenes delivering a quaternary a-chiral allylboronate product with up to 98% enantioselectivity (eq 49). 

A zinc-catalyzed borylation of unactivated alkyl halides has been achieved (Scheme 6.5) [11], Simple zinc(n) chloride was used as the metal precursor, while a moderately bulky NHC served as the supporting hgand. This chemistry was carried out at room temperature and afforded moderate to excellent yields of the alkylboronates. Similar to the copper chemistry described earlier, the zinc-catalyzed chemistry successfully functionalized a range of substrates including cyclic and acyclic alkyl halides. This system was also able to borylate several tertiary aUcyl halides, although there was some substrate specificity noted by the authors. It is also noteworthy that the authors carried out the borylation reaction under an atmosphere of air in a sealed vial and still obtained a significant amount of the alkylboronate. 

In addition to arylboronic acids, arylboronates have also been successfully used in fluorination reactions (Scheme 7.56) [93]. These boron compounds are attractive substrates since they are typically more robust than other boron species and can often be stored for long periods of time. The catalyst system for this reaction was a copper(I) triflate species along with 2 equiv of silver fluoride. While several sources of electrophilic fluorine generated the aryl fluorides, N-fluoro-2,4,6-trimethylpyridinium hexafluorophosphate was the most effective. The chemistry displayed broad functional group tolerance with the lowest yields obtained with heteroarylboronates. The authors were also able to devise a one-pot borylation-fluorination reaction starting from the parent arene. The arene was converted into an arylboronate through an iridium-catalyzed borylation reaction in the first step of the reaction, while fluorination was achieved during the second step. This is particularly attractive since it facilitates the conversion of unfunctionalized substrates into aryl fluorides. 

In this context, an internally activated, sp -sp -hybridized diboron compound, PDIPA diboron (pinacolato diisopropanolaminato diboron) prepared by Santos et al, has shown to easily interact with CuCl salts to favor the B-B cleavage and form the corresponding Cu-Bpin species (Scheme 44) which were very active in the copper-catalyzed, P-borylation of a,P-unsaturated conjugated compounds and aUenoates. " ... 

Lee JL, Kwon J, Yun J. Copper-catalyzed addition of diboron reagents to a,p-acetylenic esters efficient synthesis of p-boryl-a,p-ethylenic esters. Chem Commun. 2008 733-735. 

Dang L, Lin Z, Marder TB. DFT studies on the borylation of a,P-unsaturated carbonyl compounds catalyzed by phosphine copper(I) boryl complexes and observations on the interconversions between O- and C-bound enolates of Cu, B, and Si. Organometallics. 2008 27 4443-4454. 

Thorpe SB, Guo X, Santos WL. Regio- and stereoselective copper-catalyzed p-borylation of aUenoates by a preactivated diboron. Chem Commun. 2011 47 424—426. 

The NHC-Cu-catalyzed conjugated addition of [B(pin)]2 on a,p-unsaturated carbonyl species has also been investigated. Perez and Fernandez initially reported the p-borylation of conjugated enals. Enantioselective versions of this transformation started to emerge afterwards, but the first methods that were developed exhibited only moderate ee s. Hoveyda and McQuade in 2010, and Song and Ma in 2015 reported a series of new NHC precursors that performed the same reaction on acrylates with high efficiency and selectivity (Scheme 11.6). Similar chiral NHCs were also used by Hoveyda and McQuade in the development of copper-catalyzed enantioselective allylic substitution using [B(pin)]2 as a formal pronucleophile. 

A copper-catalyzed nucleophilic borylation of a,/3-unsaturated carbonyl compounds yielding /3-borylated carbonyl compounds in good yields has been simultaneously reported by Hosomi and coworkers [123] and Miyaura and coworkers... 

A regioselective transition metal-catalyzed cycloisomerization reaction of boron-containing alkynyl epoxides toward C-2- and C-3-borylated furans was developed. It was found that the copper catalyst as well as the gold catalyst with a relatively more basic triflate counterion favored boryl migration toward C-3-borylated furans, whereas employment of the cationic gold hexafluoroantimonate afforded C-2-borylated furans via a formal 1,2-hydrogen shift (14JA13146). 

Very recently, Ma and coworkers reported another bicyclic triazolium ligand 102 based on [2.2]paracyclophane and its applications in the asymmetric copper (I)-catalyzed p-borylation of a,p-unsaturated acyclic enones (Scheme 3.64) [93]. The catalyst generated in situ by the reaction of 102 and CU2O was remarkably efficient giving the p-boryl ketones in high yields (up to 99%) and enantioselectivities (up to 97%). A screening of the ligand revealed that the absolute... 

Hong and co-workers tested imidazolium salt L6 as an NHC precursor in the copper(I)-catalyzed conjugate borylation of various activated alkenes (Scheme 6) [28], Esters and nitriles were no suitable substrate classes for this system, giving just moderate enantiomeric excesses (lb 5b, 2a —> 6a), whereas enantioselec-tivities of amide-derived boiylated adducts were improved compared to the work of Yun [14], Enantiocontrol was good for the synthetically useful p-borylated Weinreb amide 31 and even better for NA -dialkylated amide 32. Changing the double bond geometiy from to Z led to decreased yield and selectivity (95%, 86% ee for E versus 80%, 66% ee for Z, not shown). 

Scheme 7 Conjugate borylation catalyzed by a chiral preformed 6-membered NHC-copper(I) complex introduced by McQuade...

Scheme 14 Copper(I)-catalyzed chemoselective 1,6-borylation of acyclic a.p.y.d-unsaturated...

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