Titanium allyl

High ee values have also been obtained with organometallics," including organotitanium compounds (methyl, aryl, allylic) in which an optically active ligand is coordinated to the titanium," allylic boron compounds, and organozinc compounds. 

Chiral diolato titanium allyls (Scheme 361) have been used in the synthesis of (+)-sedamine in an 11 step procedure in which the allyltitanation reaction is the key step.884 The analogous chiral crotyltitanium compound (Scheme 362) directs the nucleophilic addition to the 6V-face of aldehydes to give a mixture of diastereomeric homoallylic alcohols.885,886... 

The unsaturated cationic titanium allyl compound [Gp 2Ti(allyl)]+BPh4- is prepared by oxidation of the titanium(m) allyl complex Cp 2Ti(allyl) with a ferrocenium cation. Nucleophilic addition to the cationic unit proceeds regioselectively to the central allylic position. Reaction with benzyl Grignard or the enolate of propiophe-none affords the corresponding titanacyclobutane complexes (Scheme 513).1305... 

The isomerization process of the fulvene titanium allyl complex Cp (Fv)Ti(773-C3Fl5)1293 (Fv = CsMe4CH2) (Scheme 506 Section 4.05.4.2.1) to the 1-propenyl Cp FvTi( 71-CH=CHMe) has been investigated. Mechanistic, kinetic, and thermodynamic aspects suggest that the reaction proceeds via reversible first-order steps with the participation of four intermediates.1323... 

Disproportionation reactions, titanium complexes Biscyclopentadienyl allyls, titanium Dlhaptoacyl complexes, titanium Allyl elimination reactions, titanium complexes Biscyclopentadienyl alkyls, titanium, pyridine metalatlon reactions... 

A whole range of potentially useful products can be derived from titanium allyl complexes upon treatment with various insertable ligands followed by an aqueous work-up (Scheme 30). ... 

The first practical method for asymmetric epoxidation of primary and secondary allylic alcohols was developed by K.B. Sharpless in 1980 (T. Katsuki, 1980 K.B. Sharpless, 1983 A, B, 1986 see also D. Hoppe, 1982). Tartaric esters, e.g., DET and DIPT" ( = diethyl and diisopropyl ( + )- or (— )-tartrates), are applied as chiral auxiliaries, titanium tetrakis(2-pro-panolate) as a catalyst and tert-butyl hydroperoxide (= TBHP, Bu OOH) as the oxidant. If the reaction mixture is kept absolutely dry, catalytic amounts of the dialkyl tartrate-titanium(IV) complex are suflicient, which largely facilitates work-up procedures (Y. Gao, 1987). Depending on the tartrate enantiomer used, either one of the 2,3-epoxy alcohols may be obtained with high enantioselectivity. The titanium probably binds to the diol grouping of one tartrate molecule and to the hydroxy groups of the bulky hydroperoxide and of the allylic alcohol... 

CONJUGATE ALLYLATION OF a,g-ENONES WITH ALLYLSILANES PROMOTED BY TITANIUM TETRACHLORIDE Conditions... 

The Sharpless-Katsuki asymmetric epoxidation reaction (most commonly referred by the discovering scientists as the AE reaction) is an efficient and highly selective method for the preparation of a wide variety of chiral epoxy alcohols. The AE reaction is comprised of four key components the substrate allylic alcohol, the titanium isopropoxide precatalyst, the chiral ligand diethyl tartrate, and the terminal oxidant tert-butyl hydroperoxide. The reaction protocol is straightforward and does not require any special handling techniques. The only requirement is that the reacting olefin contains an allylic alcohol. 

In 1980, Katsuki and Sharpless communicated that the epoxidation of a variety of allylic alcohols was achieved in exceptionally high enantioselectivity with a catalyst derived from titanium(IV) isopropoxide and chiral diethyl tartrate. This seminal contribution described an asymmetric catalytic system that not only provided the product epoxide in remarkable enantioselectivity, but showed the immediate generality of the reaction by examining 5 of the 8 possible substitution patterns of allylic alcohols all of which were epoxidized in >90% ee. Shortly thereafter. Sharpless and others began to illustrate the... 

A number of reaction variables or parameters have been examined. Catalyst solutions should not be prepared and stored since the resting catalyst is not stable to long term storage. However, the catalyst solution must be aged prior to the addition of allylic alcohol or TBHP. Diethyl tartrate and diisopropyl tartrate are the ligands of choice for most allylic alcohols. TBHP and cumene hydroperoxide are the most commonly used terminal oxidant and are both extremely effective. Methylene chloride is the solvent of choice and Ti(i-OPr)4 is the titanium precatalyst of choice. Titanium (IV) t-butoxide is recommended for those reactions in which the product epoxide is particularly sensitive to ring opening from alkoxide nucleophiles. ... 

The reaction is limited to allylic alcohols other types of alkenes do not or not efficiently enough bind to the titanium. The catalytically active chiral species can be regenerated by reaction with excess allylic alcohol and oxidant however the titanium reagent is often employed in equimolar amount. 

Titanium-IV compounds with their Lewis acid activity may catalyze an interfering rearrangement of the starting allylic alcohol or the epoxy alcohol formed. In order to avoid such side-reactions, the epoxidation is usually carried out at room temperature or below. 

In light of the previous discussions, it would be instructive to compare the behavior of enantiomerically pure allylic alcohol 12 in epoxidation reactions without and with the asymmetric titanium-tartrate catalyst (see Scheme 2). When 12 is exposed to the combined action of titanium tetraisopropoxide and tert-butyl hydroperoxide in the absence of the enantiomerically pure tartrate ligand, a 2.3 1 mixture of a- and /(-epoxy alcohol diastereoisomers is produced in favor of a-13. This ratio reflects the inherent diasteieo-facial preference of 12 (substrate-control) for a-attack. In a different experiment, it was found that SAE of achiral allylic alcohol 15 with the (+)-diethyl tartrate [(+)-DET] ligand produces a 99 1 mixture of /(- and a-epoxy alcohol enantiomers in favor of / -16 (98% ee). 

The emergence of the powerful Sharpless asymmetric epoxida-tion (SAE) reaction in the 1980s has stimulated major advances in both academic and industrial organic synthesis.14 Through the action of an enantiomerically pure titanium/tartrate complex, a myriad of achiral and chiral allylic alcohols can be epoxidized with exceptional stereoselectivities (see Chapter 19 for a more detailed discussion). Interest in the SAE as a tool for industrial organic synthesis grew substantially after Sharpless et al. discovered that the asymmetric epoxidation process can be conducted with catalytic amounts of the enantiomerically pure titanium/tartrate complex simply by adding molecular sieves to the epoxidation reaction mix-... 

Figure 6.3 Diastereofacial differentiation in titanium-catalyzed AE of secondary allylic alcohols.

The AE reaction catalyzed by titanium tartrate 1 and with alkyl hydroperoxide as terminal oxidant has been applied to a large variety of primary allylic alcohols containing all eight basic substitution patterns. A few examples are presented in Table 6.2. 

The mechanism for such a process was explained in terms of a structure as depicted in Figure 6.5. The allylic alcohol and the alkyl hydroperoxide are incorporated into the vanadium coordination sphere and the oxygen transfer from the peroxide to the olefin takes place in an intramolecular fashion (as described above for titanium tartrate catalyst) [30, 32]. 

The direct allylation of 2-phenylpropanal proceeds with much lower selectivity [2-propenylmagnesium bromide 73 27 allyltrimethylsilane/titanium(IV) chloride 67 33]27. 

Allylsilanes react with carbonyl compounds to transfer the allyl group with 1,3-transposition, in the presence of Lewis acids, typically titanium(IV) chloride47. Recently this reaction has been carried out under super-acid catalysis48. Transfer of the allyl group is also induced by tetrabutylammonium fluoride, but in this case reaction takes place regioselectively at the less substituted end of the allyl fragment49. 

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