Boryl conjugate addition

The mechanism of these NHC-catalysed boryl conjugate addition reaction in the absence of transition metal complexes [113] will not be discussed here, as it is outside of the scope of this chapter. 

Scheme 40 Asymmetric tandem p-borylation-conjugate addition reaction...

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]. 

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

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). 

P-Borylation of a,P-Unsaturated imines. Fernandez and coworkers have also developed a route to y-ainino alcohols via a tandem sequence of enantioselective -borylation of a,p-unsaturated imines, followed by iterative imine reduction and boronic ester oxidation. In the presence of B2pin2, CuOTf and a binapthol-derived phosphoramidite ligand, asymmetric conjugate addition of (V-protected Q ,/3-unsaturated imines occurred in high yield and with excellent enantioselectivity. Diasteroselective reduction of the imine to the corresponding jyn-y-amino alcohol was achieved with BH3 THF (eq 56). The authors postulated that... 

Notwithstanding the extremely rich and diverse reactivity presented above, all the examples presented thus far feature the addition of an NHC catalyst onto an sp carbon. Several reactions have been developed in the last ten years describing the activation of heteroatom o bonds by NHCs [8cj. The concept can be well illustrated by the recent work of Hoveyda and coworkers, who reported boryl and silyl conjugate additions to a,P-unsaturated carbonyls (Scheme 18.35) [124]. In both cases, addition of the NHC onto a trivalent boron atom activated the B-heteroatom bond. The use of Cj-symmetric imidazolinium salt 169 in the sUyl conjugate addition led to P-silyl ketones, esters, and aldehydes in good to high enantioselectivity. 

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. 

Boryl and silyl conjugate additions, according to Hoveyda and coworkers. 

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)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>. 

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... 

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... 

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