Allyltitanium Triphenoxide1

[130004-39-6]  · C21H20O3Ti  · Allyltitanium Triphenoxide  · (MW 368.27)

(reagent for the regioselective allylation of epoxides at the most substituted carbon;2 the crotyl homolog reacts stereoselectively with aldehydes3 and ketones4)

Solubility: reactions are normally performed in THF.

Form Supplied in: not available commercially.

Preparative Methods: the reagent is prepared in situ by reacting the corresponding Grignard derivative in THF at -78 °C -> -30 °C with ClTi(OPh)3.3 The latter is prepared by refluxing Chlorotitanium Triisopropoxide and phenol in toluene, with the azeotropic removal of isopropanol. Reactions of the reagent with epoxides are normally performed at -78 °C, while reactions with aldehydes and ketones are started at -100 °C.

Organotitanium Reagents.

The conversion of allyl or crotyl organometallics to derivatives of the general type RCH=CHCH2TiX3 (X = OR´ or NR´´2) or the corresponding titanates RCH=CHCH2TiX4MgCl (X = OR´ or NR´´2) often results in significant improvements in the chemo-, regio-, diastereo-, and enantioselectivity of these reagents.1 The increased steric and electronic requirements of the titanated species lead to a synthetically useful modulation of the nucleophilicity, Lewis basicity, and Lewis acidity of these reagents. Also, in the case of crotylmetals, titanation often produces configurationally homogeneous systems, resulting in an enhanced diastereoselectivity during carbonyl additions.

Regioselective Allylation of Epoxides.

The reaction of unsymmetrical epoxides with carbon nucleophiles at their most substituted position is generally a difficult transformation. Normally these epoxides react with organocopper reagents and other similar nucleophiles in an SN2 manner at their least substituted carbon. In the case of styrene oxides (eq 1), a variety of allyltitanium derivatives,1d including CH2=CHCH2Ti(OPh)3,2 favor allylation at the most substituted epoxide carbon, presumably via an SN1-like pathway.

Similar reactivity and selectivity is usually not observed with alkyl-substituted epoxides. The use of CH2=CHCH2Ti(O-i-Pr)3 in these cases gives substantial amounts of a hydride reduction product Meerwein-Ponndorf-Verley reduction. A good reagent for this purpose, however, is CH2=CHCH2Ti(OPh)3, which gives, in high yields, almost exclusively the products of allylation at the most substituted epoxide carbon (eq 2).2

When the most substituted carbon is chiral, the reaction proceeds with a high degree of inversion of configuration (eq 3).2

Stereoselective Addition to Aldehydes and Ketones.

Although allyltitanium reagents of the general type CH2=CHCH2TiX3 (X = OR´ or NR´´2) add to carbonyl compounds in a highly chemoselective manner,1 the use of the triphenoxy derivative (X = OPh) does not offer any significant advantages over other more readily available variants (e.g. X = O-i-Pr). In the case of crotyltitanium species, however, the triphenoxytitanium derivative is one of the most diastereoselective (eq 4).3

More bulky phenolic substituents do not result in improved diastereoselectivity (eq 5).3

A similar reaction takes place with ketones, although the diastereoselectivity depends on the relative size of the large (RL) and small (RS) substituents (eq 6).4

1. (a) Reetz, M. T. Top. Curr. Chem. 1982, 106, 1. (b) Hoffmann, R. W. AG(E) 1982, 21, 555. (c) Weidmann, B.; Seebach, D. AG(E) 1983, 22, 31. (d) Reetz, M. T. Organotitanium Reagents in Organic Synthesis; Springer: Berlin, 1986. (e) Roush, W. R. COS 1991, 2, 1. (f) Ferreri, C.; Palumbo, G.; Caputo, R. COS 1991, 1, 139. (g) Yamamoto, Y.; Asao, N. CRV 1993, 93, 2207.
2. Tanaka, T.; Inoue, T.; Kamei, K.; Murakami, K.; Iwata, C. CC 1990, 906.
3. Widler, L.; Seebach, D. HCA 1982, 65, 1085.
4. Seebach, D.; Wilder, L. HCA 1982, 65, 1972.

Nicos A. Petasis

University of Southern California, Los Angeles, CA, USA

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