Ti-catalyzed processes

A case of the addition of an allylstannane to aldehydes has been reported by Tagliavini to proceed with appreciable enantioselectivity (Scheme 6.15) [40]. A notable feature of the Zr-catalyzed transformations is that they proceed more rapidly than the corresponding Ti-catalyzed processes reported by the same research team (see Scheme 6.16). Furthermore, C—C bond formation is significantly more efficient when the reactions are carried out in the presence of 4 A molecular sieves the mechanistic rationale for this effect is not known. It should be noted that alkylations involving aliphatic aldehydes are relatively low-yielding, presumably as the result of competitive hydride transfer and formation of the reduced primary alcohol. 

Scheme 6.15. Zr-catalyzed enantioselective addition of allylstannanes to aldehydes is more facile than the corresponding Ti-catalyzed processes.

Related catalytic enantioselective processes It is worthy of note that the powerful Ti-catalyzed asymmetric epoxidation procedure of Sharpless [27] is often used in the preparation of optically pure acyclic allylic alcohols through the catalytic kinetic resolution of easily accessible racemic mixtures [28]. When the catalytic epoxidation is applied to cyclic allylic substrates, reaction rates are retarded and lower levels of enantioselectivity are observed. Ru-catalyzed asymmetric hydrogenation has been employed by Noyori to effect the resolution of five- and six-membered allylic carbinols [29] in this instance, as with the Ti-catalyzed procedure, the presence of an unprotected hydroxyl function is required. Perhaps the most efficient general procedure for the enantioselective synthesis of this class of cyclic allylic ethers is that recently developed by Trost and co-workers, involving Pd-catalyzed asymmetric additions of alkoxides to allylic esters [30]. 

Related catalytic enantioselective processes [84] As the examples in Scheme 6.26 show, a wide variety of catalytic asymmetric aldol additions have been reported that can be considered as attractive alternatives to the Zr-catalyzed process summarized above. The Ti-cata-lyzed version due to Carreira (84) [85], the Cu-catalyzed variant of Evans (85) [86], and the protocol reported by Shibasaki (86) [87] have all been used in syntheses of complex molecules. More recently, Trost (87) [88] and Shibasaki (88) [89] have developed two additional attractive asymmetric catalytic aldol protocols. Other related technologies (not represented in Scheme 6.26) have been described by Morken [90] and Jorgensen [91]. 

Small amounts of these acids or other phosphorus compounds containing acidic OH groups inhibit the SSP process. This inhibition of Ti-catalyzed polycondensation is related to the formation of stable adducts between the acidic phosphorus compound and the catalyst [53], Such a problem can be overcome by the use of certain compounds, for example, nonyl phosphite, in exact, equivalent amounts [54],... 

Enantiomerically pure sulfoxides play an important role in asymmetric synthesis either as chiral building blocks or stereodirecting groups [156]. In the last years, metal- and enzyme-catalyzed asymmetric sulfoxidations have been developed for the preparation of optically active sulfoxides. Among the metal-catalyzed processes, the Kagan sulfoxidation [157] is the most efficient, in which the sulfide is enantioselectively oxidized by Ti(OzPr)4/tBuOOH in the presence of tartrate as chirality source. However, only alkyl aryl sulfides may be oxidized by this system in high enantiomeric excesses, and poor enantioselectivities were observed for dialkyl sulfides. 

Mechanistic investigations concerning the Mo(VI)-catalyzed epoxidations with alkyl peroxides as oxidants point to the similarities to the V(V)- and Ti(IV)-catalyzed processes. Of the numerous suggestions, two mechanisms are consistent with most experimental observations.244,245 278... 

As exemplified by the reactions of Schemes 1 and 4, fluorotitanium compounds could open new possibilities for metal-catalyzed processes. Their fascinating structural diversity [7] as well as further catalytic possibilities in the field of olefin polymerizations [7i, 16] have been put forward by the pioneering work of Roesky, Noltemeyer and co-workers. Similar properties were also exhibited by the analogous zirconium and hafnium compounds [7b,i]. A Zr binaphtholate has already been successfully applied for the enantioselective allylstannylation of aldehydes [2f], Buch-wald and co-workers successfully used a chiral titanocene difluoride as precursor for the corresponding Ti(lII) hydride, a very efficient catalyst for the enantioselective hydrosilylation of imines [17]. 

Chiral amines have been transformed into chiral imines RCH=NG, which are usually in equilibrium with the tautomeric enamines. These enamines undergo asymmetric alkylations, and the best results are often obtained with ethers 1.58 or with valine derivatives 1.59 (R = i-Pr, R = tert-Bu) [169, 173,253] in the presence of bases. Enamines, lithioenamines and zinc enamines derived from imines are very potent Michael donors that often participate in highly stereoselective reactions [161, 162, 169, 173, 254, 257, 260, 262, 267], Chiral imines can suffer very selective addition reactions of organomagnesium reagents [139, 253, 254] and allyl-metals [154, 258]. They also suffer stereoselective Ti-catalyzed silylcyanation [268], Strecker reaction [266], and [2+2] or [4+2] cydoadditions [131, 256, 263], When the reaction produces an imine product, the chiral auxiliary is recovered after acidic hydrolysis. However, when an amine is obtained as the product, as is often the case from phenethylamine derivatives, the chiral residue is cleaved by hy-drogenolysis. In such cases, the chiral amine is not, strictly speaking, a chiral auxiliary. But these processes will be discussed anyway because of their importance in asymmetric synthesis. 

In many catalytic processes and transition metal mediated reactions, a-bor-ane complexes have been shown to be intermediates. The bis(borane) complex Cp2Ti( 72-HBcat/)2 (HBcaT = HBcat-4-f-Bu) is a highly active catalyst for the hydroboration of vinylarenes [37]. A mechanism, shown in Scheme 3, has been proposed for the Ti-catalyzed hydroboration on the basis of a detailed mechanistic study [37]. Theoretical calculations provided further support to the proposed reaction mechanism and showed that the reductive elimination step, giving the product molecules, is rate-determining [38]. In the Cp2Ti(CO)2 catalyzed hydroboration of alkynes [36,37], the proposed reaction mechanism (Scheme 4) also involves a a-borane complex similar to 11 and 14. In the titanium-catalyzed decaborane-olefin hydroborations [47,48], a-borane complexes were also considered as intermediates. In the Cp2MH (M = Nb, Ta) mediated hydroboration reactions of olefins [39,41], Smith and his coworkers observed several interesting cr-borane complexes, such as 21-23 discussed above. 

Although the majority of research interest in enanlioselective allyUc substitution reactions has involved Pd-catalyzed processes, there have been several successful examples using other metals. These include the use of tuugsteu,f i t molybdeuum, uickel, iridium,ti and platinum-catalyzed reactions. ... 

Shi and coworkers reported an efficient kinetic resolution of racemic enol ester epoxides via a BINOL-Ti-catalyzed rearrangement process [242]. Both enantioen-riched enol ester epoxides and a-acyloxy ketones can be obtained through this... 

There have been numerous Other applications of BINOL-Ti-catalyzed ally-lation reactions in complex molecule syntheses [30, 32], In the construction of the terminal portion of mucocin, Evans documented the asymmetric addition of an allylstannane to unsaturated aldehyde 202, giving adduct 203 in 98 2 dr (Equation 14) [125]. In another example, Roush disclosed the addition of an allylstannane to aldehyde 204, en route to the synthesis of the superstolides (Equation 15) [126]. These examples underscore the Ti-cata-lyzed enantioselective allylation process as a general approach to useful, functionalized chiral fragments. 

As discussed in Sect. 5, the intermolecular hydroamination of alkynes catalyzed by group 4 metal complexes is a well-documented process. The less challenging intramolecular transformation can be achieved efficiently with various titanium-based catalysts [51, 125-130]. The cyclization proceeds analogously to the rare earth metal-catalyzed process with exclusive ej o-selectivity and often requires elevated temperatures. However, the homoleptic titanium tetraamide Ti(NMe2)4 catalyzes the cyclization of both terminal and internal aminoalkynes at room temperature (7) [126, 127]. 

Polymerization of olefins such as styrene is promoted by acid or base or sodium catalysts, and polyethylene is made with homogeneous peroxides. Condensation polymerization is catalyzed by acid-type catalysts such as metal oxides and sulfonic acids. Addition polymerization is used mainly for olefins, diolefins, and some carbonyl compounds. For these processes, initiators are coordination compounds such as Ziegler-type catalysts, of which halides of transition metals Ti, V, Mo, and W are important examples. 

In the second process the /z-paraffins are partially chlorinated with chlorine gas in a multistage reactor. The resulting product, a mixture of /z-paraffins and chloroparaffins, is fed, together with excess benzene, into a reactor where AlCl3-catalyzed alkylation is performed. The catalyst suspended or dissolved in the crude alkylate is then separated, while the benzene and unconverted ti-paraffins are recovered by distillation and recycled to the previous reaction stages. In the last step of the process, the LAB is separated from the heavy alkylates. This second process needs to be integrated with a chlorine production unit and with an additional industrial transformation plant which makes use of the corrosive HC1 byproduct. 

Besides the already described Pd-, Rh- and Ru-catalyzed transformations, many other transition metals have also been used in domino processes, albeit to a lesser extent. Co- and also Ni-catalyzed transformations constitute the largest group in this section, though other examples include Cu, W, Mo, Fe, Ti, Cr, Au, Pt, Zr, and Lanthanide-catalyzed reactions. 

Related catalytic enantioselective processes [115] Two catalytic procedures for asymmetric addition of cyanides to meso epoxides have been reported [116]. One is the result of work carried out in these laboratories, shown in Eq. 6.24, promoted by Ti-peptide chiral complexes, while the other, developed by Jacobsen and Schaus, is a Yb-catalyzed enantioselective reaction that is effected in the presence of pybox ligands (Eq. 6.25) [117]. Although the Shibasaki method (Eq. 6.21) is not as enantioselective as these latter methods, it has the advantage that it accomplishes both the epoxidation and subsequent desymmetrization in a single vessel. 

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