Ethyl Diazolithioacetate1

[55718-77-9]  · C4H5LiN2O2  · Ethyl Diazolithioacetate  · (MW 120.05)

(nucleophilic diazo species for preparation of substituted diazo esters,2-9 b-keto esters,3,6,10-12 acylalkynes,13 and for carrying out one-carbon ring expansion reactions14-16)

Alternate Name: ethyl lithiodiazoacetate.

Solubility: sol ether solvents.

Preparative Methods: prepared in situ by lithiation of Ethyl Diazoacetate using n-Butyllithium or Lithium Diisopropylamide, or by transmetalation of Hg[C(N2)CO2Et]2.

Handling, Storage, and Precautions: stable in solution only below -50 °C. Use in a fume hood.

Preparation of Diazo Esters.

Ethyl diazoacetate can be readily converted into a range of diazo esters by way of its lithio derivative. The lithium derivative can be prepared by transmetalation of diethyl mercuriobis(diazoacetate) with butyllithium at -70 °C,2 or, much more conveniently, by lithiation of commercially available ethyl diazoacetate using butyllithium2,3 or LDA.4,5 The lithio derivative reacts with a range of electrophiles (eq 1) to give substituted diazoesters (Table 1). With carbonyl compounds, better yields are often obtained if butyllithium is added to the mixture of ethyl diazoacetate and carbonyl compounds;3 acrolein undergoes exclusive 1,2-addition.5,6 Similar condensations between ethyl diazoacetate and aldehydes (or ketones) can also be carried out in the presence of potassium hydroxide.7

Other carbonyl electrophiles such as six-membered lactones,8 thiolactones,9 and N-Boc lactams8 also react with ethyl diazolithioacetate to give the corresponding diazo b-keto esters (eq 2), which in the case of the hydroxy and mercapto compounds can be recyclized to the corresponding seven-membered heterocycles by treatment with Dirhodium(II) Tetraacetate.8,9

Preparation of b-Keto Esters and Related Compounds.

Addition of ethyl diazolithioacetate to aldehydes gives a-diazo-b-hydroxy esters (see above). Treatment of these with HCl,3,10 rhodium(II) acetate,11 or various other metal salts12 results in loss of nitrogen and the formation of b-keto esters (eq 3). A variation on the reaction involves acetylation of the intermediate hydroxy diazo compound, followed by pyrolysis to give the enol acetate of the b-keto ester;6 hydrogenation of the hydroxy diazo ester over palladium gives b-hydroxy esters (eq 3).6

Preparation of Acylalkynes.

In contrast to the above reactions of a-diazo-b-hydroxy esters (eq 3), reaction of these species with Boron Trifluoride Etherate gives alkynic esters (eq 4).13

Ring Expansion Reactions.

The conversion of a-diazo-b-hydroxy esters derived from aldehydes into b-keto esters involves H-migration (eq 3); an analogous reaction of a-diazo-b-hydroxy esters derived from cyclic ketones would therefore result in a one-carbon ring expansion reaction. This has been successfully used for simple cyclic ketones (eq 5),3 and for chromanones and their thio derivatives (eq 6).14,15 Thiopyrylium salts can be similarly ring expanded.16

Related Reagents.

Other metalated derivatives of ethyl diazoacetate are known,1 e.g. the silver derivative is readily converted into substituted diazo esters by alkylation (eq 7).17

t-Butyl diazoacetate is also readily lithiated; quenching with lactones gives products entirely analogous to the ethyl ester (eq 2).18

Diazolithioacetone can be generated from Diazoacetone using butyllithium or LDA and participates in similar reactions to ethyl diazolithioacetate. Thus addition to aldehydes gives a-diazo-b-hydroxy ketones, treatment of which with rhodium(II) acetate gives b-diketones (eq 8),19 or with boron trifluoride etherate to give acetylalkynes (cf. eq 4).13

1. For a review on organometallic derivatives of diazo compounds, see: Kruglaya, O. A.; Vyazankin, N. S. RCR 1980, 49, 357.
2. Schöllkopf, U.; Frasnelli, H. AG(E) 1970, 9, 301.
3. Schöllkopf, U.; Bánhidai, B.; Frasnelli, H.; Meyer, R.; Beckhaus, H. LA 1974, 1767.
4. Pellicciari, R.; Natalini, B.; Cecchetti, S.; Fringuelli, R. JCS(P1) 1985, 493.
5. Padwa, A.; Kulkarni, Y. S.; Zhang, Z. JOC 1990, 55, 4144.
6. Wenkert, E.; Ceccherelli, P.; Fugiel, R. A. JOC 1978, 43, 3982.
7. Wenkert, E.; McPherson, C. A. JACS 1972, 94, 8084.
8. Moody, C. J.; Taylor, R. J. JCS(P1) 1989, 721.
9. Moody, C. J.; Taylor, R. J. T 1990, 46, 6501.
10. Pellicciari, R.; Castagnino, E.; Corsano, S. JCR(S) 1979, 76.
11. Pellicciari, R.; Fringuelli, R.; Ceccherelli, P.; Sisani, E. CC 1979, 959.
12. Nagao, K.; Chiba, M.; Kim, S.-W. S 1983, 197.
13. Pellicciari, R.; Castagnino, E.; Fringuelli, R.; Corsano, S. TL 1979, 481.
14. Pellicciari, R.; Natalini, B. JCS(P1) 1977, 1822.
15. Pellicciari, R.; Natalini, B.; Taddei, M.; Ricci, A.; Bistocchi, G. A.; de Meo, G. JCR(S) 1979, 142.
16. Nakasuji, K.; Kawamura, K.; Ishihara, T.; Murata, I. AG(E) 1976, 15, 611.
17. Schöllkopf, U.; Rieber, N. CB 1969, 102, 488.
18. Davies, M. J.; Moody, C. J.; Taylor, R. J. JCS(P1) 1991, 1.
19. Pellicciari, R.; Fringuelli, R.; Sisani, E.; Curini, M. JCS(P1) 1981, 2566.

Christopher J. Moody

Loughborough University of Technology, UK

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