Allyltitanium reagents

In general, there are three main types of allyltitanium reagent, usually prepared in situ from allyllithium or allylmagnesium derivatives ... 

Only few allyltitanium reagents bearing a removable chiral auxiliary at the allylic residue are known. The outstanding example is a metalated 1-alkyl-2-imidazolinone14, derived from (—)-ephedrine, representing a valuable homoenolate reagent. After deprotonation by butyllithium, metal exchange with chlorotris(diethylamino)titanium, and aldehyde or ketone addition, the homoaldol adducts are formed with 94 to 98% diastereoselectivity. 

Alkylidenecydopropane derivatives can readily be prepared by the reaction of 1 with vinylcyclopropyl carbonates and subsequent trapping of the resulting allyltitaniums with aldehydes or ketones (Eq. 9.24) [44], It should be noted that, in this case, the carbon—carbon bond formation occurs at the less substituted allylic terminus, and not at the more substituted end of the titanium reagent, the latter being the position at which addition to substituted allyltitanium reagents is usually observed. 

The preparation of chiral allyltitanium reagents having a stereogenic center and their utilization in asymmetric synthesis have been pursued. As shown in Eq. 9.27, chiral allyl-... 

The synthesis of optically active compounds by the diastereoselective reaction of allyltitanium reagents with chiral electrophiles has also been reported. The reaction of allyltitanium reagents with chiral imines proceeds with excellent diastereoselectivity, as shown in Eq. 9.28, thus providing a new method for synthesizing optically active homoallylic amines with or without a P-substituent [51,52],... 

Generation and Reaction of Allyltitanium Reagents (Section 9.3) 2-(4-Bromophenyl)-l-phenyl-3-buten-l-ol [42] To a solution of l-(4-bromophenyl)allyl ethyl carbonate (285 mg, 1.0 mmol) and Ti(OiPr)4 (0.296 mL, 1.0 mmol) in diethyl ether (5 mL) was added iPrMgBr (1.20 m in diethyl ether, 2.0 mmol) at 50 °C. The resulting yellow solution was stirred at —50 to —40 °C for 1.5 h, in the course of which it became brown. Benzaldehyde (74.3 mg, 0.70 mmol) was then added at —40 °C and the mixture was allowed to warm to 0 °C over a period of 30 min. After the addition of aqueous 1 n HC1 (5 mL) at this temperature, the mixture was allowed to warm to ambient temperature. The organic layer was separated and the aqueous layer was extracted with diethyl ether (10 mL). The combined organic layers were washed with saturated aqueous NaHC03 solution (5 mL), dried over... 

Table 3. Chemoselective Addition of Allyltitanium Reagents to Aliphatic Carbonyl Compounds 90)...

D.III.3 Addition of Substituted Allyltitanium Reagents to Aldehydes and Ketones... 

The Cp() ,f )-Ti[All] and Cp(S,S)-Ti[All] reagents have been condensed with a variety of aldehydes always with good enantios-electivities (eqs 4-11). The degree of enantioface discrimination of these allyltitanium reagents is very high. The Si face attack is preferred for the Cp(/f,/f)-Ti[All] reagent and the Re face attack is preferred for the Cp(S,S)-Ti[All] reagent. 

Allyltitanation of Aldehydes. The two-stage, one-pot procedure involves first the generation of the allyltitanium reagents (Jt)-(2a-f) (eq 1) by transmetalation of allyl-Grignard or allyl-Li compounds with a slight excess (1.2 equiv) of It is ad-... 

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 conqtlex (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 interestii 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 function 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). ... 

As far as the stereoselectivity of the addition is concerned, allyltitanium reagents, unlike their alkyl analogs (Section 1.5.3.1.3), give preferentially axial addition to 4-r-butylcyclohexanone. The selectivity... 

The reaction between a wide variety of (alkylthio)allyltitanium reagents of type (11) and carbonyl compounds has also been reported (equation 9). Table 1 illustrates how the relative proportions of a- and y-adduct formed vary according to the reagent. 

Cohen et al. have extensively studied the generation and reactivities of allylcerium leagents. - Allylcerium reagents react with a,p-unsaturated carbonyl compounds in a 1,2-selective fashion. It is particularly noteworthy that unsymmetrical allylcerium reagents react with aldehydes or enals mainly at the least-substituted terminus, as opposed to other allylorganometallics such as allyltitanium reagents. An example is shown in Scheme 13. ... 

The lithiation of ethyl allyl sulfide followed by transmetallation with titanium isopropoxide engenders an allyltitanium reagent formulated as (26 Scheme 8). This and related reagents add to aldehydes or ketones to afford hydroxy sulfides, which are converted to epoxides as shown. The power of this method for the stereoselective generation of even trisubstituted epoxides is evident from Scheme 8 and equation (18). Reagent (26a), prepared as shown in Scheme 8a, undergoes addition to ketone (26b) to afford product exclusively resulting from chelation-controlled diastereofacial addition (as a mixture of epimers at the position shown). ... 

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