Steric and electronic effects on the reduction of O-silylated aromatic ketoximes with borane

Article abstract of DOI:10.1016/S0040-4039(00)01109-6

4-Methoxy acetophenone oximes substituted at the oxygen with TMS, TBS, TIPS and MDPS groups were reduced with borane-THF obtaining the 4-methoxy-N-ethyl aniline as the principal product, up to a 95% yield in the case of the more hindered TIPS group. The 2-methoxy- and 2,4-methoxyacetophenone O-TBS oximes produced only the rearranged secondary aniline. Reduction of 1-indanone O-TBS oximes afforded only the tetrahydroquinoline, whereas the 2-indanone analog provided only 2-aminoindan. (C) 2000 Elsevier Science Ltd.

Full text of DOI:10.1016/S0040-4039(00)01109-6

Tetrahedron Letters 41 (2000) 6567±6570
Steric and electronic e€ects on the reduction of O-silylated
aromatic ketoximes with borane
Margarita Ortiz-Marciales,* Dyliana Figueroa, Jose A. Lopez, Melvin De Jesu
and Rafael Vega
 s
Department of Chemistry, University of Puerto Rico, Humacao College, CUH Station, Humacao, PR 00791, USA
Received 18 April 2000; revised 26 June 2000; accepted 28 June 2000
Abstract
4-Methoxy acetophenone oximes substituted at the oxygen with TMS, TBS, TIPS and MDPS groups
were reduced with borane±THF obtaining the 4-methoxy-N-ethyl aniline as the principal product, up to a
95% yield in the case of the more hindered TIPS group. The 2-methoxy- and 2,4-methoxyacetophenone O-TBS
oximes produced only the rearranged secondary aniline. Reduction of 1-indanone O-TBS oximes a€orded
only the tetrahydroquinoline, whereas the 2-indanone analog provided only 2-aminoindan. # 2000
Elsevier Science Ltd. All rights reserved.
Keywords: primary amines; secondary anilines; silyloxime rearrangement.
Amines are very important organic compounds widely used as intermediates for the synthesis
of a diversity of pharmaceutical1 and polymeric products.2 Therefore, synthetic methodologies
for particular amines have evolved through the years from diverse precursors,3 with di€erent
advantages and outcomes.4 Primary amines have been conveniently prepared by the reduction of
oximes and oxime derivatives using a variety of reagents and catalysts,3,5 7 due mainly to the
facile synthesis of oximes and oxime ethers from readily available carbonyl compounds.
The reduction of aromatic oxime ethers by borane and organoboron reagents often a€ords
good yields of the hydroxyl amine or the amine, depending on the structure and reaction
conditions.8 10 However, Liu et al.11 observed high yields of unidenti®ed side-products from the
reduction of 6-benzyloxy-2,3-dihidrobenzofuran oxime ethers with borane±norephedrine, in
particular for the case of the O-trimethyl silylated derivative. Recently, we reported the formation
of N-ethylanilines in the reduction of 4-substituted acetophenone O-TBS oximes with borane in
THF under re¯ux conditions.12 The yield of the expected arylalkylamine with respect to the
secondary aniline depended strongly on the electronic e€ects of the para substituents (Scheme 1).
* Corresponding author. Tel: 852-3222; fax: 850-9422; e-mail: m_ortiz@cuhac.upr.clu.edu
0040-4039/00/$ - see front matter # 2000 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(00)01109-6

6568
Scheme 1.
We now wish to report on the steric and electronic e€ects of silicon substituents observed in the
borane reduction of 4-methoxyacetophenone silylated oximes that led us to reexamine the
mechanism proposed for the formation of secondary anilines.
In Table 1 the results are shown for the borane reduction of O-TMS-, TBS-, TIPS- and MDPS
4-methoxyacetophenone oximes. The reductions were carried out at 60ꢀC with 2 equivalents of
.
BH3 THF, except for the O-TIPS oxime, which was reduced slowly and required 3 equivalents to
complete the reaction. As the size of the substituents on silicon increased, the yield of the N-ethyl-
4-methoxy aniline obtained increased, up to 95% for the TIPS moiety. These results indicate that
bulkier substituents on silicon hinder the normal reduction of the hydroxyl amine intermediate
that produces the primary amine and, consequently, the migration of the electron-rich aryl group
to the electron-de®cient nitrogen is favored, a€ording the aniline after the reduction of the
cationic intermediate. The intervention of a Beckmann rearrangement, as in the reduction of
oxime sulfonates with the trialkylaluminum±diisobutylaluminum hydride (DIBAL) reagents,13 is
not envisioned, since the silicon substituents hinder the coordination of the borane molecule to
the oxygen of the oxime ether, inhibiting it to act as a Lewis acid and hence to induce the cleavage
of the nitrogen±oxygen bond.
Table 1
Reduction of aromatic silylated oximes using BH3 THF
.
Also of interest was the investigation of the electronic e€ect of 2- and 2,4-methoxy groups on
the aromatic ring of O-TBS acetophenone oximes, as well as the possible ring expansion of O-TBS
substituted 1- and 2- indanone oximes for the formation of important heterocyclic systems. We

6569
observed with the acetophenone oximes that the electron donating methoxy groups substantially
increased the rearranged products, obtaining only the N-ethyl anilines in moderate to good yields.
These anilines are remarkably unstable and the isolated yields were moderate (Table 2).
Table 2
Synthesis and borane±THF reduction of O-TBS aromatic ketoximes
Contrasting results were found in the reduction of 1- and 2- indanone O-TBS oximes. Thus, the
former provided only tetrahydroquinoline in excellent yield, while 2-indanone oxime produced
only 2-aminoindane. As in previous studies of the reduction of cyclopentanone and cyclohexanone
O-TBS oximes, no trace of the rearranged secondary amine was detected.12 Thus, the borane
reductive rearrangement takes place only for aromatic silylated oximes, in particular with
electron donating substituents in the ortho position.
Moreover, the synthetic utility of these new procedures can be directed conveniently for the
synthesis of acyclic and cyclic aniline products for the following reasons: (1) silylated oximes are
readily prepared from oximes; (2) O-TBS oximes are very stable and easy to puri®ed; and (3) a
facile borane reduction procedure that with a simple isolation process produces mainly anilines
with high purity.
Acknowledgements
This work was supported by the National Institute of Health MBRS Program (GM 08216) and
AREA Grant (GM 59829). The NSF-CIRE-PUMP and NSF-AMP undergraduate's support is

6570
also gratefully acknowledged. We thank Mr. Jose Martõnez (University of Puerto Rico, Rõo Piedras)
for obtaining the NMR spectra.
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