Zinc Complex Reducing Agents1

NaH-t-C5H11ONa-ZnX2
(NaH)

[7646-69-7]  · HNa  · Zinc Complex Reducing Agents  · (MW 24.00) (t-C5H11ONa)

[14593-46-8]  · C5H11NaO  · Zinc Complex Reducing Agents  · (MW 110.15) (ZnCl2)

[7646-85-7]  · Cl2Zn  · Zinc Complex Reducing Agents  · (MW 136.29) (Zn(OAc)2.2H2O)

[5970-45-6]  · C4H10O6Zn  · Zinc Complex Reducing Agents  · (MW 219.53)

(zinc-containing complex reducing agents (ZnCRAs); reduces many functional groups1)

Physical Data: light gray solid of uncertain structure containing Zn0 species.2

Solubility: insol organic solvents.

Preparative Methods: t-C5H11ONa-ZnCRA (x.y.z) is conveniently prepared by the reaction of t-C5H11OH (y equiv) with a mixture of Sodium Hydride (x + y equiv) and ZnX2 (X = Cl, OAc) (z equiv) in THF or DME. Commercial NaH (55-60% in oil) is used after three washings with anhydrous THF or DME under N2. t-C5H11OH is distilled from sodium. ZnX2 is dried in vacuo (15 mmHg) for 16 h at 100-110 °C.

Handling, Storage, and Precautions: ZnCRAs are nonpyrophoric but are handled and stored under inert atmosphere (N2 or, better, Ar). Hydrolysis must be performed by slow addition of cold water or EtOH to destroy the reagent.

Designation.

t-C5H11ONa-ZnCRA (x.y.z) means a reagent obtained from x, y, and z equivalents of NaH, t-C5H11ONa, and ZnX2 (X = Cl, OAc), respectively.

Reduction of Organic Halides.

t-C5H11ONa-ZnCRAs are very mild and thus selective reducing agents. They are appreciably less basic than NaH and t-C5H11ONa.

t-C5H11ONa-ZnCRA (4.2.1) reduces alkyl halides in THF or DME (primary >> secondary >>> tertiary and I > Br >> Cl). Moreover, benzyl halides are easily reduced while vinyl halides are unreactive. Thus selective reductions may be easily performed, as exemplified in eqs 1 and 2.3

Ketones and nitriles are tolerated during the reduction of reactive halides (eqs 3 and 4).3

Reduction of Ketones.

t-C5H11ONa-ZnCRA (4.1.1) alone or, better, in the presence of Magnesium Bromide (electrophilic assistance), easily reduces saturated ketones under mild conditions and in very good yields.4,5 Although able to reduce hindered ketones, the reagent is sensitive to steric hindrance, leading to stereoselective reductions (eqs 5 and 6).5

t-C5H11ONa-ZnCRA (4.1.1) does not reduce carbon-carbon double bonds and is well suited for the selective reduction of a,b-unsaturated ketones to the corresponding allylic alcohols.6

Efficiency and chemoselectivity of t-C5H11ONa-ZnCRA may be considerably improved by addition of Chlorotrimethylsilane (ZnCRASi).7 Thus ketones as well as highly enolizable aldehydes are very rapidly reduced in excellent yields (eqs 7 and 8). The stereoselectivity of ZnCRASi broadly resembles one ZnCRA.5 t-C5H11ONa-ZnCRASi is highly chemoselective in the reduction of the carbonyl groups of ketones and aldehydes in the presence of carbon-carbon double bonds (eqs 9 and 10).

Finally, excellent chemoselectivity was also found during the reduction of aldehydes and ketones in the presence of halides, acetals, and nitro aromatic derivatives, as illustrated in eqs 11 and 12.8

ZnCRAs and especially ZnCRASis are more efficient and chemoselective than NiCRAs (see Nickel Complex Reducing Agents) in the reduction of ketones and aldehydes.

Reduction of Epoxides.

t-C5H11ONa-ZnCRA (4.2.1) reduces epoxides regioselectively at the less substituted carbon atom (eq 13).9

With less reactive epoxides, the constitution of the reagent must be changed and a (8.2.1) ratio of the constituents is necessary.9 The regioselectivity is not changed under such conditions (eq 14). Interestingly, the regioselectivity of these reductions is opposite to that observed with NiCRAs.

Reduction of Aromatic Nitro Compounds.

In the presence of MgBr2, t-C5H11ONa-ZnCRA (7.1.1) selectively reduces a number of aromatic nitro compounds to their azoxy derivatives in good to excellent yields (eqs 15 and 16).10 A few percent of azo derivatives are sometimes also produced. Note that under such conditions NiCRAs lead to the corresponding anilines.


1. (a) Caubère, P. Top. Curr. Chem. 1978, 73, 50. (b) Caubère, P. AG(E) 1983, 22, 599. (c) Caubère, P. PAC 1985, 57, 1875. (d) Caubère, P. Rev. Heteroatom Chem. 1991, 4, 78.
2. Brunet, J. J.; Besozzi, D.; Courtois, A.; Caubère, P. JACS 1982, 104, 7130.
3. Vanderesse, R.; Brunet, J. J.; Caubère, P. JOC 1981, 46, 1270.
4. Brunet, J. J.; Mordenti, L.; Caubère, P. JOC 1978, 43, 4804.
5. (a) Feghouli, A.; Fort, Y.; Vanderesse, R.; Caubère, P. TL 1988, 29, 1379. (b) Fort, Y.; Feghouli, A.; Vanderesse, R.; Caubère, P. JOC 1990, 55, 5911.
6. Mordenti, L.; Brunet, J. J.; Caubère, P. JOC 1979, 44, 2203.
7. Brunet, J. J.; Besozzi, D.; Caubère, P. S 1982, 721.
8. Feghouli, G.; Vanderesse, R.; Fort, Y.; Caubère, P. SC 1990, 20, 849.
9. Fort, Y.; Vanderesse, R.; Caubère, P. TL 1985, 26, 3111.
10. Feghouli, G.; Vanderesse, R.; Fort, Y.; Caubère, P. JCS(P1) 1989, 2069.

Paul Caubère

Université Nancy I, France



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