|
The α-hydroxycarbonyl
moiety is an important structural motif in organic synthesis and is present in a
substantial number of natural products. A variety of methods have been
developed to prepare this functionality including α-oxygenation of enolates with
electrophilic oxidizing agents as well as dihydroxylation or epoxidation of enol
ethers.1
Recently, aminooxylation of aldehydes 2
and ketones3
has been demonstrated using nitrosobenzene. However, this latter protocol
requires a large excess of the carbonyl compound in tandem with syringe pump
techniques which diminishes from the usefulness of the transformation.
Nicholas Tomkinson of
Cardiff University (UK) recently reported several practical reagents for
preparation of α-oxygenated carbonyl compounds.4
N-tert-butyl-O-benzoylhydroxylamine hydrochloride (669407)
is a bench stable reagent for α-functionalization of a variety of aldehydes
under mild conditions (Scheme 1). The reaction can be performed in open
air and in the presence of moisture. Benzoylation occurs in high yield at both
secondary and tertiary centers as demonstrated by the reactions of this reagent
with isovaleraldehyde and cyclohexanecarboxaldehye (Figure 1).
While this reagent is only
useful on aldehyde substrates, a similar bench stable reagent can be applied
towards the α-oxygenation of ketones. Treatment of cyclohexanone with N-methyl-O-benzoylhydroxylamine
hydrochloride (669393)
in water provides the benzoyl-protected alcohol in excellent yield, presumably
through a pericyclic rearrangement of an intermediate iminium ion (Scheme 2).
A previous synthesis of this molecule from cyclohexanone by House required a laborious five-step
procedure.5
Both acyclic and
cyclic ketones undergo oxidation at mild temperatures to afford protected
alcohols in good to excellent yield (Scheme 3, Figure 2). The
reagent is tolerant of existing functionality (e.g. sulfonamides, free hydroxyl
groups, and unsaturation), and in the case of non-symmetrical ketones, oxidation
occurs regiospecifically at the more substituted carbon. In addition to water
and DMSO, THF and CHCl3 can also be used as solvents with similar
yields.
Sigma-Aldrich is
delighted to add these new α-benzoylation tools to our growing arsenal of
oxidation reagents.
Product Information
| Product # |
Product Name/Description |
Structure |
Add to Cart |
|
669407 |
N-tert-Butyl-O-benzoylhydroxylamine
hydrochloride, 97% |
 |
|
|
669393 |
N-Methyl-O-benzoylhydroxylamine
hydrochloride, 97% |
 |
|
References:
(1) Chen, B.-C. et
al. Org. React. 2003, 62, 1.
(2) (a) Brown, S.
P. et al. J. Am. Chem. Soc. 2003, 125, 10808. (b) Zhong,
G. Angew. Chem., Int. Ed. 2003, 42, 4247. (c) Hayashi,
Y. et al. Tetrahedron Lett. 2003, 44, 8293.
(3) (a) Bøgevig,
A. et al. Angew. Chem., Int. Ed. 2004, 43, 3317. (b)
Hayashi, Y. et al. Angew. Chem., Int. Ed. 2004, 43,
1112. (c) Córdova, A. et al. Chem. Eur. J. 2004, 10,
3673.
(4) (a) Beshara, C.
S. et al. Chem. Commun., 2005, 1478. (b) Beshara, C. S. et al.
Org. Lett. 2005, 7, 5729.
(5) House, H. O.;
Richey, F. A. J. Org. Chem. 1969, 34, 1430.
|
