[63115-45-7]  · C2H3NO2  · Nitrosocarbonylmethane  · (MW 73.06)

(ene reactions and [4 + 2]cycloadditions)

Solubility: sol commonly used organic solvents.

Preparative Method: prepared in situ by oxidation of acetohydroxamic acid with tetrapropylammonium periodate.

General Discussion.

Nitrosocarbonylmethane, like other acylnitroso compounds, is an exceptionally reactive substance which must be generated in situ. It participates in a variety of reactions, most notably [4 + 2] cycloadditions and ene reactions. A review by Kirby summarizes much of the early work on this class of compounds.1

Two methods for generation of nitrosocarbonylmethane have been most commonly employed. The first is via oxidation of acetohydroxamic acid. Tetraalkylammonium periodates such as Tetra-n-butylammonium Periodate or tetrapropylammonium periodate have been widely used for this process. Keck examined tetraethyl-, tetrapropyl-, and tetra-n-butylammonium periodates and found the tetrapropylammonium periodate to provide the best balance between ease of preparation and solubility properties. Commonly used solvents include DMF, CHCl3, and CH2Cl2.

Nitrosocarbonylmethane generated in this way undergoes [4 + 2] cycloaddition with simple dienes in which the nitroso moiety functions as the dienophile (eq 1).

Oxidation of acetohydroxamic acid in the presence of 9,10-dimethylanthracene leads to the Diels-Alder adduct in good yield. As originally demonstrated by Kirby, this [4 + 2] adduct serves as a very convenient source of nitrosocarbonylmethane under strictly neutral nonoxidizing conditions. Thus (1) is a crystalline solid which is easily purified and stable upon storage as the solid; however, heating to 80-110 °C in solution results in release of nitrosocarbonylmethane (and 9,10-dimethylanthracene) (eq 2).1 The nitrosocarbonylmethane can be employed as a dienophile with other dienes present.

Diels-Alder adducts of other simple nitrosocarbonyl compounds with 9,10-dimethylanthracene can be utilized in similar fashion.

Nitrosocarbonylmethane also participates in ene reactions with appropriate alkenes, and here generation of nitrosocarbonylmethane from (1) is preferred. Keck and Yates have provided several examples of ene reactions of simple alkenes using this method (eqs 3 and 4).2

Diels-Alder adduct (1) is very useful in the preparation of other more complex nitrosocarbonyl compounds. Keck has demonstrated that the lithium enolate of (1) can be generated uneventfully with Lithium Diisopropylamide and used in a variety of alkylation and condensation reactions (eq 5). This methodology thus provides a surrogate for the enolate of nitrosocarbonylmethane, which is, of course, inaccessible by direct means.

Keck and co-workers have utilized this methodology to effect intramolecular [4 + 2] cycloadditions and intramolecular ene reactions of such substituted derivatives of nitrosocarbonylmethane.3 For example, condensation of (2) with sorbaldehyde affords (3); subsequent heating of (3) in refluxing benzene then affords (4) in very high yield (eq 6).

In a synthesis of (+)-perhydrohistrionicotoxin, Keck and Yates used this approach to effect an intramolecular type ene reaction (eq 7).4

Additional selected examples of this methodology, i.e. utilization of enolate (2) to construct substrates for intramolecular Diels-Alder reactions or ene reactions of substituted derivatives of nitrosocarbonylmethane, are shown (eqs 8 and 9).5

The N-O bond in such Diels-Alder or ene products is easily cleaved reductively. Reagents commonly employed include Zinc-Acetic Acid, Aluminum Amalgam, Sodium Amalgam, Titanium(III) Chloride, and various catalytic hydrogenation protocols. The ease of this reduction, and the possibility for hydroxylation of the C=C double bond produced in the [4 + 2] cycloaddition, has made this a popular strategy for the synthesis of numerous polyhydroxylated nitrogen containing compounds.

For nitrosocarbonylmethane itself, the regioselectivity of bimolecular Diels-Alder reactions is often low. For example, reaction with 1-t-butyldimethylsilyloxybutadiene leads to a 1:1 mixture of regioisomeric Diels-Alder adducts (eq 10).6

Kirby has also noted the formation of a very unusual product upon reaction of nitrosocarbonylmethane with dienamine (5) (eq 11).7

Related Reagents.

Benzyloxyhydroxamic Acid.

1. Kirby, G. W. CSR 1977, 1, 6.
2. Keck, G. E.; Yates, J. B. TL 1977, 48, 4627.
3. Keck, G. E.; Nickell, D. G. JACS 1980, 102, 3632.
4. Keck, G. E.; Yates, J. B. JOC 1982, 47, 3590.
5. (a) Keck, G. E.; Webb, R. R. JACS 1981, 103, 3173. (b) Keck, G. E.; Webb, R. R.; Yates, J. B. T 1981, 37, 4007.
6. Streith, J.; Pires, J.; Defoin, A. SL 1990, 2, 111.
7. Kirby, G. W.; Freer, A.; Islam, A.; Mahajan, M. H. 1989, 28, 147.

Gary E. Keck & Anandan Palani

University of Utah, Salt Lake City, UT, USA

Copyright 1995-2000 by John Wiley & Sons, Ltd. All rights reserved.