Titanium(III) Chloride

TiCl3

[7705-07-9]  · Cl3Ti  · Titanium(III) Chloride  · (MW 154.23)

(aqueous functional group reducing agent; after reducing to low-valent species, reductive coupling reagent of carbonyls to vicinal diols and alkenes)

Physical Data: mp 440 °C (dec); d 2.640 g cm-3.

Solubility: sol water, alcohol; insol diethyl ether, CHCl3, CCl4, CS2, benzene.

Form Supplied in: dark red-violet solid; dimethoxyethane complex, TiCl3.1.5DME [18557-31-8], solution in CH2Cl2/THF, solution in hydrochloric acid.

Purification: sublimation of solid at 1 mmHg.1b

Analysis of Reagent Purity: aqueous solutions of TiCl3 can be titrated against 0.1 N cerium(IV) sulfate.2

Handling, Storage, and Precautions: dry powder is pyrophoric in air; moisture sensitive; reacts violently with water, and causes skin burns. Heating in vacuo over ca. 450 °C gives TiCl2 and TiCl4. Use in a fume hood and in a dry box under inert atmosphere. TiCl3.(DME)1.5 is air sensitive, but can be stored indefinitely under Ar at room temp. Reactions involving low-valent titanium should be run under argon.1

Introduction.

The low-valent titanium species (Ti0/TiI) generated from TiCl3 are very useful for reductive coupling of aldehydes and ketones to give vicinal diols and further to alkenes. Aqueous TiCl3 is used for the reduction of various functional groups (-SO, -NO2, -NHOR, -X).

Reductive Coupling.3-8

The reagent composition of the low-valent species (Ti0/TiI) to be used in the coupling reaction depends on the reducing conditions for its generation. TiCl3 and Lithium Aluminum Hydride in a 1:0.6 molar ratio produces a Ti0 species, and the molar ratio 1:0.5 a TiI species.4 Other reducing agents such as Lithium,9,10 Sodium,9 Potassium-Graphite (C8K),11 Magnesium,9,12,13 Zinc/Copper Couple12 and Rieke titanium have been applied to TiCl3.14 Low-valent titanium species can also be obtained from Titanium(IV) Chloride by similar reductive procedures.4 THF is usually the preferred solvent in the reductive coupling reactions, although other solvents such as dioxane or dimethoxyethane have also been used. The reaction should be performed under argon. The reagents and solvents must be pure and absolutely dry, since traces of oxidation or hydrolysis products can interfere. Variable yields in closely related reactions, and reactions difficult to reproduce, have been ascribed to aged and ineffective batches of TiCl3. The variable nature of TiCl3 samples is overcome by prior conversion of TiCl3 into a dimethoxyethane complex, TiCl3.(DME)1.5. The complex is readily purified by crystallization.7 According to McMurry et al., the optimized titanium reagent for the reductive carbonyl coupling is prepared by the Zn/Cu couple reduction of TiCl3.(DME)1.5.7

Mechanism of Carbonyl Coupling.

The reducing metal adds an electron to the oxo group and the anion radical dimerizes in a pinacol reaction (eq 1). The intermediate pinacols can be isolated at low temperature (0 °C), and are dehydroxylated at higher temperature (60 °C) to alkenes on the surface of zero-valent titanium particles.7 For the reductive pinacol formation, Samarium(II) Iodide is an alternative.15

Intermolecular Coupling.

The reaction is most suitable for the preparation of symmetrical alkenes by joining two of the same carbonyl compounds, and is an excellent method for coupling of aliphatic carbonyl compounds (eq 2).8 It is also an effective method for the synthesis of highly strained alkenes (eqs 3 and 4).16

Mixed Coupling.

A mixture of two different carbonyl compounds will generally react to afford a nearly statistical mixture of alkenes. However, by applying an excess of one carbonyl compound, mixed couplings can be synthetically useful (eq 5).17

Intramolecular Coupling.

Coupling of a,o-dicarbonyl compounds gives cycloalkenes (eq 6).7 Difficult intramolecular couplings leading to medium- and large-ring cycloalkenes require a lengthy addition time to achieve high dilution, and the use of 4 or more equiv of titanium per carbonyl group.

Keto-ester couplings work well for five- to seven-membered ring formation. The product is the corresponding ketone.18 Functional group compatibility includes acetal, alcohol, alkene, alkylsilane, amine, ether, halide, sulfide, and vinylsilane; incompatible are allylic alcohol, 1,2-diol, epoxide, halohydrin, a-halo ketone, nitro group, oxime, and sulfoxide.3

Reductions.6

Aqueous TiCl3 is a very useful reagent for the reduction of oximes to imines. The imines are rapidly hydrolyzed to carbonyl derivatives at low pH, and the overall reaction is a mild, rapid, and efficient deoximation procedure.19 CrII 20 and VII 21 reagents have also been used for this purpose. The usefulness is exemplified by a synthesis of a vicinal tricarbonyl system via an oxime which is readily available by nitrosation of the 1,3-dioxo derivative (eq 7).22

The reaction with a-hydroxyimino-b-keto esters may also lead to pyrazine formation.23 With added Sodium Borohydride, amine formation has been used in the synthesis of a-amino acids.24 By analogy to the oxime reduction, aliphatic nitro compounds are transformed into carbonyl derivatives. Reduction of the nitro group gives the corresponding nitroso derivative, with subsequent tautomerism to the oxime which reacts further as above (eq 8).25

Aromatic and heteroaromatic nitro compounds are also reduced to amines under mild conditions.26 Buffered aqueous TiCl3 can also be used to reduce hydroxamic acids, cyclic or acyclic (eq 9).27 The ready cleavage of N-O bonds is attributed in part to titanium's high affinity for oxygen. Accordingly, sulfoxides are also deoxygenated cleanly and in high yields to the corresponding sulfides.28

a-Halo ketones are dehalogenated by TiCl3.29 A number of reductive transition metal complexes,30 as well as SmI2,31 possess this ability. TiCl3 is commercially available and therefore a convenient reagent. Halogen atoms in aromatics can also be removed by aqueous TiCl3. Both halo- and cyanopyridines are reduced to pyridines with aqueous TiCl3,32 which should find wide application in heterocyclic chemistry (eq 10).

Highly electrophilic and polarized carbon-carbon double bonds can also be reduced with aqueous TiCl3 (eq 11).33

Related Reagents.

Niobium(V) Chloride-Zinc; Samarium(II) Iodide; Titanium(III) Chloride-Potassium; Titanium(III) Chloride-Lithium Aluminum Hydride; Titanium(III) Chloride-Zinc/Copper Couple.


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Lise-Lotte Gundersen

Norwegian College of Pharmacy, Oslo, Norway

Frode Rise & Kjell Undheim

University of Oslo, Norway



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