Conjugate borylation

Additions of silicon nucleophiles are similar to conjugate borylation. Hoveyda showed that Cu complexes with chiral carbene ligand 240 are excellent catalysts... 

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... 

More recently, a copper-bifluoride complex has been described, starting once again from the alkoxide species. Subsequently, [Cu(NHC)2] [HF2] complexes were developed (Figure 8.2) [91]. Both complexes were highly air stable in the solid state and moderately stable in solution compared to their analog [Cu(F) (IPr)] [92]. Remarkably, catalytic activity was observed in several transformations such as the reduction of ketones, the 1,4-conjugated borylation and silylation, and the diastereoselective allylation. 

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...

Different from the work of Oestreich and co-workers, the Sato group prepared chiral a-silyl amines with the aid of the simple diphenylethylenediamine ligand L3 (Scheme 20) [50]. L3 had already been used in conjugate borylation by the Shibasaki group [18]. Although levels of enantiomeric excess were somewhat lower than those obtained with Oestreich s protocol, a broad range of aldimines was converted successfully [96a-d- (/ )-97a-d]. Furthermore, the obtained... 

Conjugate Borylation of a, p-unsaturated aldehydes. More challenging substrates for conjugate boryl addition are Q ,/9-unsaturated aldehydes, as 1,2-addition is competitive with the desired 1,4-addition. Fernandez and coworkers achieved the first Cu-catalyzed version of this reaction through the use of an alkoxy Cu-NHC complex under base-free conditions. The alkoxy Cu-NHC complex, as opposed to the chloride analog typically employed for this reaction class, was more catalytically active and chemoselective for the 1,4-addition. The alkoxy group... 

Scheme 2.31 Copper-catalysed asymmetric borylation of conjugated enones...

Finally, the fourth approach (path d) involves the generation of conjugated nitro olefins C from the starting AN by known methods. The latter are involved in the conjugated [1,4]-addition to give target nitronates. This process is of most importance for the synthesis of six-membered cyclic nitronates (see Section 3.2.1.2.2). This method was also used to prepare a small series of boryl-, silyl-and acyl nitronates (see Sections 3.2.3 and 3.2.4). It is beyond reason to believe that all possibilities of the approach (d) are exhausted by these examples. 

Bis(pinacolato)diboron 14 and bis(neopentyl glycolate)diboron 15 have been used for rhodium-catalyzed conjugate addition to a,/ -unsaturated ketones giving /9-boryl ketones, though the asymmetric version has not been reported [15]. 

Bis(pinacolato)diborane(4) selectively adds to terminal aikenes and cyclic aikenes having internal strain to provide bis(boryl)alkanes in 76-86% yields 85-89 in the presence of a catalytic amount of Pt(dba)2 at 50 °C67 (Scheme 16). It is interesting to mention that Pt(dba)2 directed 1,2-addition to certain conjugated dienes, whereas 1,4-addition through a 7i-allyl-platinum(II) intermediate is an energetically more favorable process. The 1,4-addition to penta-1,3-diene at 80 °C with Pt(PPh3)4 gives 90, but the same reaction with Pt(dba)2 selectively produced the 1,2-addition product 91 at room temperature (Scheme 16). 

Another interesting application of Jt-conjugated systems is their use as chemosensors. For example, a modified dithienophosphole oxide 160 (see Scheme 49 for the synthesis of its precursor) that incorporates boryl-end caps is a very sensitive and selective sensory material for the fluoride ion (Scheme 126). Treatment of this derivative by fluoride induces a red shift of the emission maximum (160, 452 nm 373, 485 nm) that is visible to the naked eye. This shift in the fluorescence emission can even be detected down to micromolar concentrations of fluoride ion notably, the addition of other halides (CP, Br, P) does not affect the fluorescence in any way <20060L495>. 

The conjugate addition can use bis(pinacolato)diboron to prepare p-boryl esters and amides/ ... 

Analogously, copper(I) salts cleave diboron compounds [e.g., bis(pinacolato)diboron] to give, in the presence of an a,/3-enone, the corresponding conjugate boration product (eq 113). In contrast to the silylation procedure, reactions can be run at room temperature both on cyclic and acyclic enones. Subsequent oxidation of the borylated ketone provides the /3-hydroxyketone. 

The first Cu-catalyzed asymmetric borylative cyclization reaction between cyclohexadienone-containing 1,6-enynes and B2pin2 was established to afford an optically pure d5-hydrobenzo[l ]furan framework bearing alkenylboronate and enone substructures through a tandem process of selective P-borylation of the propargylic ether and subsequent enantioselective conjugate addition to cyclohexadienone (13JA11700). 

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