Titanium ate complexes

C.VII Controlled Reversal of Chemoselectivity using Titanium Ate Complexes... 

Allyltitanium complexes (22) readily add to carbonyl compounds with high regio- and stereo-selection. They are prepared by reaction of a chlorotitanium complex (21) with an allyl-magnesium or -lithium derivative (equation 13). Some of these unsaturated Ti complexes, like (23)-(25) in Scheme 2, obtained from allylmagnesium halides or allyllithium by reaction with titanium tetraisopropoxide or titanium tetramides, are known as titanium ate complexes . The structure of these ate complexes, at least from a formal point of view, can be written with a pentacoordinate Ti atom. Some ate complexes have synthetic interest, as is the case of (allyl)Ti(OPr )4MgBr which shows sharply enhanced selectivity towards aldehydes in comparison with the simple (allyl)Ti(OPr )3. ... 

A few examples of chemoselective additions of allyltitanium reagents to aliphatic and aromatic carbonyl compounds are reported in Table 7. Appreciable chemoselectivity toward the aldehydic function is achieved by the titanium ate complex (23), whereas the reverse chemoselectivity toward ketones is realized using aminotitanium complex (104) and the analogous ate complexes (24) and (25), as is shown in Table 7. This is very interesting since it represents a rare case of chemoselectivity in favor of carbanion addition to ketones. A tentative explanation of this inverse chemoselection considers a fast transfer of the aminyl ligand onto the aldehyde faction which becomes protected , as in (105), and thus unreactive in respect to the keto group. Ketones react also selectively compared with esters, as is shown by the reaction of ethyl levulinate (1) with the ate complex (23 equation 40). ... 

Treatment of the titanium- ate complex, ( 75-C5H5)Ti p-rf r/2-C2(SiMe i)2 2Mg(r/ -C5H5) 192,112 with excess acetylene furnishes the divalent titanium cyclohexadienyl complex, (if-l, 2,4,5,6-pentakis(trimethylsilyl)-cyclohexadienyl)(77S-cyclopentadienyl)titanium 193 (Equation (2)).113 A series of related compounds prepared from /-butylethyne, cyclohexylethyne, 1-hexyne, and phenylethyne have also been synthesized. 

Aldol reactions. Titanium -ate complexes effect anri-selective aldolization (5 examples, 72-81%). 

TBDMSCl-assisted Reaction. TBDMSCI is suitable for the activation of electrophiles in the conjugate addition of titanium ate complexes of ketone enolates to o , -unsaturated ketones. Under such conditions only a stoichiometric amount of the ate complex is required to achieve comparable 3delds, with no loss of diastereoselectivity. ... 

The titanium- ate complexes of a-methoxy allylic phosphine oxides, generated in situ by reaction of the corresponding lithium anion and Ti(0-i-Pr)4, condense with aldehydes exclusively at the a-position to produce homoallylic alcohols in a diastereose-lective fashion. The overall result is the three-carbon homologation of the original aldehyde, and this protocol has been used in a synthesis of (-)-aplysin-20 from nerolidol. The titanium- ate complex produced by reaction of the chiral lithium anion of an ( )-crotyl carbamate with Ti(0- -Pr)4 affords -y-condensation products (homoaldols) on reaction with aldehydes. Allyl anions produced by the reductive metalation of allyl phenyl sulfides condense with a,p-unsaturated aldehydes in a 1,2-manner at the more substituted (a) allyl terminus in the presence of Ti(0-i-Pr)4. 1,2-Addition of dialky Izincs to a,p-unsaturated aldehydes can be achieved with useful levels of enantiocontrol when the reaction is conducted using a chiral titanium(IV) catalyst in the presence of Ti(0- -Pr)4 (eq 20). Higher ee values are observed when an a-substituent (e.g. bromine) is attached to the substrate aldehyde, but a -substituent cis-related to the carbonyl group has the opposite effect. 

Allyltitanium ate complexes.8 In contrast to organotitanium compounds, which are aldehyde selective, the chemoselectivity of allyltitanium ate complexes depends on the ligands attached to titanium. The most aldehyde-selective allyltitanium ate complex prepared to date is CH2=CHCH2Ti[OCH(CH3) >].jMgCl (1) which reacts... 

Titanium enolates. These enolates have generally been prepared by transmet-talation of alkali-metal enolates or silyl enolate ethers. Surprisingly, Evans et al. find that a titanium enolate can be prepared directly from the oxazolidinone 1 by reaction with TiCl4 (1 equiv.) in CH2C12 and shortly thereafter with ethyldiisopropyl-amine (or triethylamine) at 0°. The enolate may actually be an ate complex (2a)... 

Upon testing the effect of other ligands at titanium, we came across some unexpected results 90). The amino derivative 102, prepared from 96 and IS, reacts in situ preferentially with ketones. In case of 26 and 82 the 100 101 ratio is 22 78 (Table 3). The in situ reaction of the related compound 104 leads to a 13 87 ratio. By using the ate complexes 106, 108 and 110, the ketone-selectivity turned out to be 4 96, 2 98 and 14 86, respectively ... 

Quenching the anion 225 with titanium tetraisopropoxide 2 affords the ate complex 226, which reacts 100% regio- and distereoselectively with aldehydes to afford the threo adducts 227 (>95% conversion, 80% isolated by distillation)90) (Equation 71). This methodology is simpler than analogous reactions of boron reagents122). Furthermore, even ketones react threo-selectively (Equation 72)90). Since the adducts can be converted by adds (anti elimination) or KH (syn elimination) into the two possible diastereomeric dienes122), the sequence is synthetically useful. 

Active polymerization catalysts have been derived from organomagnesium compounds, for example by reaction with titanium (tv) chloride [7] the polymerization of various vinyl monomers has been initiated by organomagnesium compounds [8] and recently polymerization initiated by magnesium ate complexes has been described [9, 10]. 

The reverse regiocontrol, giving 1,2-diols, is observed with DIBAL-H (diisobutylaluminum hydride). The remarkable effect of titanium tetraisopropoxide as an additive to lithium borohydride has also been reported. In this reaction benzene is a better solvent than THF, probably because a Ti complex using both oxygens in epoxy alcohols is formed in benzene before the hydride attack. Other metal hydrides used include sodium hydrogen telluride (NaHTe) and an ate complex derived from DIBAL-H and butyllithium, both of which reduce epoxides to alcohols, although they have been tested with only a small number of examples. In the former case the reaction may proceed via a 2-hydroxyalkyltellurol intermediate. 

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