Titanium-catalysed reactions

The titanium-catalysed reaction is highly chemoselective for epoxidation of allylic alcohols. Thus, the dienol 47 gave only the epoxide 48 (5.58). The reaction is also tolerant of many different functional groups, including esters, enones, acetals, epoxides, etc. 

BINOL ligands 41a-c bearing dendritic wedges at the 6,6 positions were used in titanium-catalysed reaction of tributylallyl stannane and benzaldehyde (Scheme 7.33). Whereas the yield was low, the enantioselectivity was similar to the reaction with BINOL (87% enantiomeric excess), whatever the size of the dendritic moieties. However, no attempt to recycle the catalyst or the ligand was described by the authors. 

Titanium-catalysed reaction of cyclohexyl hydroperoxide with alkenes involves two pathways, epoxidation of alkene and thermal decomposition of the hydroperoxide. The formation of radicals seems to play a role in both reactions. Epoxidation was found to take place solely at the catalyst. Absorption spectroscopy provided proof for the formation of titanium-hydroperoxide species as the active catalytic site for the direct epoxidation reaction. ... 

The dependence of the diastereomeric ratio on the choice of Lewis acid can be understood when considering the geometry of the Lewis acid complex. In the case of the titanium tetrachloride catalysed reaction, the interaction of the ester and the catalyst is strongly supported by the first crystal structure observed of the Lewis acid with a chiral dienophile (Figure 4)118. 

Another study by Fleming and coworkers examined the stereoselectivity of the titanium tetrachloride catalysed reaction of the allylsilane 137 with 1-adamantyl chloride... 

A serious shortcoming of TS-1, in the context of fine chemicals manufacture, is the restriction to substrates that can be accommodated in the relatively small (5.lx5.5 A2) pores of this molecular sieve, e.g. cyclohexene is not epoxidised. This is not the case, however, with ketone ammoximation which involves in situ formation of hydroxylamine by titanium-catalysed oxidation of NH3 with H202. The NH2OH then reacts with the ketone in the bulk solution, which means that the reaction is, in principle, applicable to any ketone (or aldehyde). Indeed it was applied to the synthesis of the oxime of p-hydroxyacetophenone, which is converted, via Beckmann rearrangement, to the analgesic, paracetamol (Fig. 1.24) [75]. 

Titanium complexes are often encountered in Lewis acid-catalysed reactions. This is certainly true for catalysed aldol reactions. Mikami and Matsukawa demonstrated that titanium/BINOL complexes e.g. complex (7.20) afforded high yield and enantioselectivity in the aldol reactions of thioester ketene silylacetals with a variety of aldehydes. In contrast to some of the aldol reactions described above, the stereochemistry of the adducts is dependant on the geometry of the enol ether. Thus, reaction of the (B)-enol ether (7.21) with aldehyde (7.22) yields the sy -aldol adduct (7.23) predominantly while the (Z)-e.no ether (7.24) results in isolation of the anti-adduct (7.25) as the major product. The authors invoke a closed silatropic ene transition state (structure (7.26) for syn-transition state), substantiated by suitable crossover experiments, to explain the diastereoselectivities... 

Tetrahedral silicate frameworks also appear to be able to include small amounts of tin, which is then able to change coordination from tetrahedral to octahedral. Like titanium, variable coordination tin imparts activity in Lewis-acid-catalysed reactions (Section 9.2.2). 

Since the development of titanium silicate (TS-1) materials as catalysts in the 1980s, heterogeneous titanium-catalysed oxidation reactions utilising aqueous hydrogen peroxide have been used in many effective and versatile reactions such as olefin epoxidation, " alcohol oxidation and phenol hydro)q7lation, which adhere more closely to the principles of green chemistry. 

Cross-coupling X Scheme 5.1 Titanium-catalysed cross-coupling reactions. 

Scheme 5.2 Titanium-catalysed intra- and intermolecular hydroaminoallg lation reactions.

Scheme 5.3 Titanium-catalysed Barbier-type reactions.

Titanium-catalysed inter- and intramolecular hydroamination of olefins and allq nes is an attractive carbon-heteroatom bond-forming reaction as it is 100% atom economical (Scheme 5.5). As hydroamination reactions catalysed by early transition metals and main-group metals have been recently re-viewed, we will only cover titanium-catalysed hydroamination reactions since 2014. 

Titanium-catalysed multicomponent reactions for the formation of JV-heterocyclic rings. 

Scheme 5.10 Titanium-catalysed dehydrogenation reactions of amine-borane adducts.

Scheme 5.11 Titanium-catalysed hydrophosphination and hydrosilylation reactions...

Scheme 5.12 Titanium-catalysed nucleophilic substitution reactions.

---