Titanium catalyse

The full paper on titanium-catalysed asymmetric epoxidation appeared in 1987 [6], once the improved catalytic procedure in the presence of molecular sieves had already been fully developed [5]. On the other hand, excellent "autobiographic" accounts have also been published in which "Everything You Ever Wanted to Know About the Discovery of Asymmetric Epoxidation" is honestly and vividly exposed by K. Barry Sharpless [4] [7]. 

The asymmetric oxidation of sulphides to chiral sulphoxides with t-butyl hydroperoxide is catalysed very effectively by a titanium complex, produced in situ from a titanium alkoxide and a chiral binaphthol, with enantioselectivities up to 96%342. The Sharpless oxidation of aryl cinnamyl selenides 217 gave a chiral 1-phenyl-2-propen-l-ol (218) via an asymmetric [2,3] sigmatropic shift (Scheme 4)343. For other titanium-catalysed epoxidations, see Section V.D.l on vanadium catalysis. 

The enthalpies of combustion, formation, and isomerization of car-2-ene and car-3-ene have been reported 335 the activation energy for the titanium-catalysed first-order isomerization of car-3-ene into car-4-ene and various menthadienes is 20kcalmor1 at 150—160 °C.336 Isomerization of car-3-ene over metal oxide catalysts varies substantially depending upon the metal catalyst used 337 other Russian work reports diene formation from the vapour-phase isomerization of car-3-ene but this Reporter is unable to assess the significance of the work from Chemical Abstracts in the absence of the original paper.338... 

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]. 

The most important example of stoichiometric asymmetric oxidation is probably the titanium-catalysed conversion of sulfides into sulfoxides by cumene hydroperoxide in the presence of stoichiometric diethyl tartrate. A simple example is the efficient asymmetric synthesis of methyl p-tolyl sulfoxide 162, an important starting material for much sulfoxide-controlled asymmetric synthesis.30... 

Benzylic Grignard reagents, derived from the corresponding styrenes by nickel- or titanium-catalysed hydromagnesation, can be carboxylated to provide an alternative anion-based approach to phenylacetic acids. 1... 

The original report on the titanium-catalysed asymmetric epoxidation of allylic alcohols (Sharpless system) prescribed stoichiometric amounts of the titanium tartrate catalyst in the general procedure and many applications of this asymmetric epoxidation have been carried out using stoichiometric or near-stoichiometric amounts of the catalyst. Sharpless has reported the first general procedure for the asymmetric epoxidation of allylic alcohols using catalytic ( <10 %) amounts of titanium(IV) isopropoxide and diethyl tartrate. 

Trimethylsilane in the presence of palladium gives 1,4-dihydro-1-trimethylsilylpyr-idine, together with silylated dimer titanium-catalysed hydrosilylation produces a tetrahydro-derivative cleanly. ... 

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. 

As well as rhodium-catalysed hydrosilylation, asymmetric ruthenium and titanium-catalysed hydrosilylation have also been reported. Amongst these, Buchwald s report of the hydrosilylation of ketones using titanocene catalysts and inexpensive polymethyUiydrosiloxane (PMHS) appear to be the most general. 

BINOL is an effective ligand in the titanium-catalysed asymmetric addition of alkynylzinc reagents to aldehydes. Aromatic, aliphatic and a,P-unsaturated aldehydes such as (6.35) are converted into the propargylic alcohol with 91-99% ee using the alkynylzinc, generated from phenylacetylene and diethylzinc. Carriera and coworkers have developed an enantioselective alkynylzinc addition that is also... 

Titanium. Catalyses of hydrogenation of alkenes, alkynes, carbonyl-, and nitro-compounds have been described. The effect of the nature of the ligand L and of the alkene to be reduced on reactivity in catalytic hydrogenation by Ti(7r-C5H5)2L2 has been quantitatively studied. The dependence of rate constants on solvent for reduction of decene in the presence of Ti(7r-C5H5)Me+ is interpreted in terms of electrostatic interaction between the active ionic species and the solvent. There is also a thermochemical report relevant here, and that is of a determination of the heats of mixing of cyclohexene and of hex-l-ene with titanium tetrachloride. The heats of mixing are close to zero, which implies very small heats of complex formation between these alkenes and titanium. ... 

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 complexes have been shown to be active for the synthesis of cyclic carbonates or either di- or trithiocarbonates from epoxides and either carbon dioxide or carbon disulfide (Scheme 5.6). Titanium-catalysed synthesis of cyclic carbonates has been recently reviewed by North and coworkers. Titanium-salen complexes find application as catalysts, in combination with tetrabutylammonium bromide or tributylamine, for the synthesis of di- or trithiocarbonates from epoxides and carbon disulfide. It is worth highlighting that the catalyst loading can be reduced to 0.5 mol%, although 1 mol% of catalyst was required in order to achieve quantitative yields. The catalyst system showed a preference for dithiocarbonate formation for most of the epoxides studied. 

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.

Another way to prepare a reusable catalyst was proposed by Venkataraman. The ligand 25, bearing a linear polyethyleneglycol (PEG) moiety (MW 5 kDa) was used in the titanium-catalysed addition of tri-methylsilyl cyanide to benzaldehyde (Figure 7.1). The silylated cyanohydrin was obtained in more than 95% yield and 86% enantiomeric excess after 24 h at room temperature, with only 0.1 mol% of catalyst. The titanium-salen complex was separated from the reaction mixture by dialysis by means of a Soxhlet apparatus. 

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. 

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