O,O-Dilithio-1-nitropropene1

[-]  · C3H5Li2NO2  · O,O-Dilithio-1-nitropropene  · (MW 100.96)

(reacts with electrophiles at the b-position; electrophiles may be alkyl halides, aldehydes, ketones, a,b-unsaturated aldehydes and ketones, esters, and nitroalkenes1-10)

Alternate Name: N,N-[bis(lithioxy)]-1-propenylamine.

Preparative Methods: generated by a,b-double deprotonation of nitroalkanes with BuLi or LDA.

Generation of Reagents (1) from Suitable Nitroalkanes.

Treatment of nitroalkanes with excess strong base may lead to a,a- or a,b-double deprotonation (eq 1). With simple nitroalkanes (2) (R = H or alkyl) the isomeric dilithio derivatives (1) and (3) can be generated selectively by reversing the mode of addition of the reagents. The lithium lithionitronate (3) is formed when 2 equiv n-Butyllithium are added to a solution of the nitroalkane in THF/HMPA or N,N-Dimethylpropyleneurea (DMPU) at -90 °C,6,11 while the bis(lithioxy)enamine (1) is generated when the nitroalkane is added to the solution of 2 equiv BuLi under otherwise identical conditions (eq 2).10 With nitroalkanes (4) bearing an additional acidifying group R2 in the b-position, such as vinyl4 or aryl2,3,5 or methoxycarbonyl,3,6,7 the base (BuLi2-5 or Lithium Diisopropylamide3,6,7) can be added to the nitroalkane solution for the a,b-double deprotonation. If there is just one a-nitro CH proton in (4) (R1 &neq; H), only a,b-deprotonation can occur; in this case, 1 equiv of BuLi is used for the first deprotonation, followed by 1 equiv of t-Butyllithium for the second deprotonation.8,9 In Table 1 the conditions for different nitroalkanes are listed. The solutions of reagents (1) are all colored from light yellow to deep red; they are stable for some hours at temperatures below -50 °C. The structure of reagents (1) is unknown; thus in the formulae used herein they are shown with both lithiums at oxygen, because of the known affinity of lithium for oxygen.

Reactions of a,b-Doubly Deprotonated Nitroalkanes with Electrophiles.

The chemistry of doubly lithiated methyl 3-nitropropanoate (1) (R = CO2Me) is covered in the article on Methyl 3-Nitropropanoate. The reagents (1) are formally enamines with two LiO substituents on nitrogen; they are much more reactive nucleophiles than normal enamines and have been called super-enamines.2 These reagents are also, formally, doubly reduced nitroalkenes (other reagents are formally doubly reduced unsaturated carbonyl compounds;1c,1d,12 we have occasionally called such systems LUMO-filled p-systems1c). As outlined in eq 3, they provide nucleophilic reactivity in the b-position of a nitro group. Nitroalkenes, on the other hand, are highly reactive electrophiles, so that the reactivity of the dilithio derivatives (1) constitutes an umpolung13 of nitroalkene reactivity (eq 3).

An example of the preparation of a homo-nitroaldol from a simple nitropropane is shown in eq 4.10 The nitroalcohol (5) is isolated in 77% yield, with essentially no isomeric ordinary nitroaldol being formed; the diastereomer ratio (dr) is poor (2.6:1).

More complex nitroalcohols of this type are produced when nitrocyclopentane and nitrocyclohexane are doubly lithiated and added to benzaldehydes to give (6) (40% yield, dr = 4:1) and (7) (32% yield, dr > 20:1),8 or when 1,1,1-trifluoro-2-nitropropane is employed (see (8) in eq 5) (20% yield, dr = 3:1).9 A special demonstration of the reactivity umpolung is the preparation of an unsymmetrical 2,3-diaryl-1,4-dinitrobutane (9) from 2-phenylnitroethane and a 2-arylnitroethylene (65% yield) (eq 6).5

Finally, in eq 7 the reactivity of the butadiene derivative (10) is outlined; from the bright red solutions of this reagent and electrophiles the isomeric 2-vinylnitroalkanes and 1-nitro-2-alkenes are obtained in varying ratios.4 Remarkably, only the regioisomer resulting from reaction at the 4-position is formed in the Michael addition to cyclic (five- through seven-membered ring) and open-chain a,b-enones.4,14 The product (11), isolated in ~50% yield with cyclohexenone, has been converted to the 1,7-dicarbonyl derivative (12) by Nef reaction4,14 carried out under the McMurry conditions.15

Related Reagents.

Lithium a-Lithiomethanenitronate; Methyl 4-Nitrobutanoate; Methyl 3-Nitropropanoate; Nitroethane.


1. (a) Seebach, D.; Colvin, E. W.; Lehr, F.; Weller, T. C. C 1979, 33, 1. (b) Döpp, D.; Döpp, H. MOC 1990, E14b, 780. (c) Seebach, D. Pohmakotr, M. T 1981, 37, 4047. (d) Thompson, C. M.; Green, D. L. C. T 1991, 47, 4223. (e) Ono, N. In Nitro Chemistry; Feuer, H.; Nielsen A. T., Eds.; VCH: New York, 1990; Chapter 1. (f) Wade, P. A.; Giuliano, R. M. In Nitro Chemistry; Feuer, H.; Nielsen, A. T., Eds.; VCH: New York, 1990; Chapter 2.
2. Henning, R.; Lehr, F.; Seebach, D. HCA 1976, 59, 2213 (CA 1976, 85, 176 754t).
3. Seebach, D.; Henning, R.; Lehr, F.; Gonnermann, J. TL 1977, 1161.
4. Seebach, D.; Henning, R.; Lehr, F. AG(E) 1978, 17, 458.
5. Seebach, D.; Henning, R.; Gonnermann, J. CB 1979, 112, 234 (CA 1979, 91, 19 168m).
6. Mukhopadhyay, T.; Seebach, D. HCA 1982, 65, 385.
7. Seebach, D.; Henning, R.; Mukhopadhyay, T. CB 1982, 115, 1705.
8. Brändli, U.; Eyer, M.; Seebach, D. CB 1986, 119, 575.
9. Beck, A. K.; Seebach, D. CB 1991, 124, 2897 (CA 1992, 116, 40 553c).
10. (a) Yamada, K.; Tanaka, S.; Kohmoto, S.; Yamamoto, M. CC 1989, 110. (b) Tanaka, S.; Kohmoto, S.; Yamamoto, M.; Yamada, K. NKK 1989, 1742 (CA 1990, 112, 178 190f).
11. Seebach, D.; Lehr, F. HCA 1979, 62, 2239 (CA 1980, 92, 75 654z).
12. Bossler, H. G.; Seebach, D. HCA 1994, 77, 1124.
13. Seebach, D. AG(E) 1979, 18, 239.
14. For further examples and details, see: Henning, R. Dissertation, Universität Giessen, 1978.
15. Ho, T. L.; Wong, C. M. S 1974, 196.

Roger E. Marti & Dieter Seebach

Eidgenössische Technische Hochschule, Zürich, Switzerland



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