Chemoselectivity, in metal-catalysed

A wide range of other reactions have been exploited in the final cyclisation ( pairing ) step in addition to the examples illustrated here, lactamisa-tions, metal-catalysed cyclisations and cycloadditions have, for example, been exploited to yield final product scaffolds. At its most powerful, the build-couple-pair strategy can allow the combinatorial variation of the scaffolds of small molecules. However, a significant challenge will be to identify reactions other than olefin metathesis that have the broad scope and chemoselectivity needed to yield scores of different ring systems. It is certainly possible that the overall approach may, in the future, be used to prepare small molecule libraries based on hundreds, or even thousands, of distinct molecular scaffolds. 

Hydroarylation, (addition of H-Ar, Ar = aryl), of alkynes, catalysed by Pd(OOCCH3)2 or Pd(OOCCFj)j in acetic acid, is an atom-economic reaction, giving rise to substituted c/i-stilbenes (Fujiwara reaction). Catalytic conversions and improved chemoselectivity to the mono-coupled product under mild conditions can be achieved by modification of the metal coordination sphere with NHC ligands. Hydroarylation of mesitylene by ethylpropiolate (Scheme 2.19) catalysed by complex 107 (Fig. 2.18) proceeds in good conversions (80-99%, 1 mol%) under mild conditions at room temperature. 

Remarkably, the heterogenisadon process can confer dramatically enhanced activity on the metal complex. Thus, the dimolybdenum complex [Mo2(MeCN)8][BF4]-Si02 prepared by direct reaction of silica with the metal complex is unusual in its ability to catalyse the polymerisation of norbomene in the absence of an aluminium co-catalyst and at moderate temperatures.165 Sol-gel processing of the ruthenium complex m-Cl(H)Ru(CO)(P)3 (where P is a coordinated ether-phosphine) with tetraethoxysilane and [Al(0-i-Pr)3] gives a stable material with moderate surface area which is active in the hydrogenation of fraras-crotylaldehyde with reasonable chemoselectivity to the carbonyl reduced products, cis- and trans-crotyl alcohol.166... 

Since simple ketones typically coordinate more weakly to metals than olefins, many Rh-phosphane complexes may show poor activity for the hydrogenation of simple ketones. However, the catalytic properties of cyclometalated half-sandwich Rh(lII) complexes 99-101, isolated or prepared in situ firom metal precursors and optically pure secondary amines, were evaluated, among which the complex 100 showed the highest productivity in the reduction of acetophenone with a i-PrOH/t-BuOK reductant system (Fig. 26) [93]. The complex 99 afforded good yield of alcohol products from acetophenone, but the enantioselectivity was low, while the cyclometalated imine 101 was almost inactive. The rhodacycle 100, which was formed in situ, efficientiy catalysed the reduction of substrates 102 (92 % ee), 103 (93 % ee) and 104 (91 % ee), with substrate 103 showing total chemoselectivity. For substrates 105,106 and 107, however, lower ee values were observed (<85 %). 

---