Benzyloxyhydroxamic Acid

[3426-71-9]  · C8H9NO3  · Benzyloxyhydroxamic Acid  · (MW 167.16)

(precursor to a benzyloxy nitroso carbonyl compound which can function as a dienophile in Diels-Alder reactions1)

Physical Data: mp 65-70 °C.

Solubility: sol water; slightly sol organic solvents.

Form Supplied in: solid; widely available.

Benzyloxyhydroxamic acid generates benzyl nitrosoformate upon oxidation with a tetraalkylammonium periodate. Treatment of in situ generated benzyl nitrosoformate with dienes gives cyclic adducts in good yield. Baldwin and co-workers reported the first total synthesis of tabtoxin by utilizing the Diels-Alder reaction of a benzyl nitrosoformate with a suitable cyclohexadiene.1 Thus ethyl cyclohexa-1,3-dienecarboxylate reacted with benzyl nitrosoformate (generated in situ from N-benzyloxyhydroxamic acid and tetraethylammonium periodate) to yield a single isomer (eq 1). The resulting adduct was then converted to tabtoxin in a few steps.

Recently, Hudlicky2 and Martin3 have successfully used [4 + 2] cycloaddition of benzyl nitrosoformate with a substituted cyclohexadiene in synthetic studies directed toward lycoricidine (eqs 2 and 3).

The dimethyl acetals of (E)-2,4-pentadienal and (E,E)- and (E,Z)-2,4-hexadienals undergo regio- and stereospecific cycloaddition reactions with benzyl nitrosoformate (eq 4).4 Similarly, this reagent reacts with a 1-silyloxy diene to give regioisomeric cycloadducts in good yield (eq 5).5

Martin has reported that benzyloxyhydroxamic acid, as well as other hydroxamic acids such as Benzohydroxamic Acid and phenylacetohydroxamic acid, is smoothly oxidized to the corresponding acylnitroso compound under Swern conditions ((COCl)2, DMSO, CH2Cl2; then NEt3) at -78 °C. This protocol has also been used to generate chiral nitroso carbamates, which afford [4 + 2] cycloadducts in excellent yield and with high diastereomeric excess (eq 6).6

Related Reagents.

Benzohydroxamic Acid; Nitrosocarbonylmethane.

1. Baldwin, J.; Patrick, D. B.; Gallacher, G.; Singleton, K. A.; Wallace, P. M. CC 1984, 40, 3695.
2. (a) Hudlicky, T.; Olivo, H. F. TL 1991, 32, 6077. (b) Hudlicky, T.; Olivo, H. F. JACS 1992, 114, 9694.
3. Tso, H.; Martin, S. F. H 1993, 35, 85.
4. Streith, J.; Geffroy, G.; Fritz, H.; Defoin, A. HCA 1988, 71, 1642.
5. Streith, J.; Defoin, A. HCA 1991, 74, 1653.
6. Martin, S. F.; Hartmann, M.; Josey, J. A. TL 1992, 33, 3583.

Gary E. Keck & Anandan Palani

University of Utah, Salt Lake City, UT, USA

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