MoO2Cl2(dmf)2-Catalyzed
Domino Reactions of ω-Nitro Alkenes to 3,4-Dihydro-2H-1,4-benzothiazines and Other Heterocycles
Chandi C. Malakar, Elena Merisor, Jürgen Conrad, Uwe Beifuss* Bioorganische Chemie, Institut für
Chemie, Universität Hohenheim, Garbenstr. 30, 70599 Stuttgart, Germany Fax: +49(711)45922951; e-Mail: ubeifuss@uni-hohenheim.de;
Further Information
Publication History
Received
6 April 2010 Publication Date: 30 June 2010 (online)
Using the transformation of allyl 2-nitrophenyl thioethers
to 3,4-dihydro-2H-1,4-benzothiazines
as an example the reductive cyclization of ω-nitroalkenes
to saturated N-heterocycles can be performed highly selective and
with high yields if a combination of MoO2Cl2(dmf)2 as
a catalyst and Ph3P as reducing agent are employed.
General Procedure
for the Synthesis of Thioethers 7a-d
In an
oven dried 250 mL three-necked round-bottom flask 2-nitro
thiophenol 9 (16.11 mmol) was dissolved
in freshly distilled dry THF (50 mL) under Ar. Sodium hydride (80%) (24.16
mmol) was added in several portions at 0 ˚C during 10
min, and after complete addition the reaction mixture was stirred
for 30 min at 0 ˚C. Freshly distilled allyl bromide (64.44
mmol) was added dropwise at 0 ˚C; after complete addition
the reaction mixture was allowed to stir at r.t. for 12.5 h. Then
the reaction mixture was poured into sat. NH4Cl (100
mL) and extracted with TBME (3 × 100
mL). The combined organic phases were washed with brine (100 mL) and
dried over anhyd MgSO4. The solvents were removed under
reduced pressure, and the crude product was purified by Kugelrohr
distillation or by flash column chromatog-raphy on silica gel (cyclohexane-EtOAc,
20:1).
General Procedure
for the (EtO)3P-Mediated Domino Reaction under Microwave Conditions
A
10 mL process vial was charged with a mixture of 7 (1 mmol),
(EtO)3P (1.07 mL, 6 mmol) and toluene (3 mL). The vial
was sealed, placed into the cavity of the microwave reactor, and
irradiated with microwaves at 200 ˚C for 30-35 min,
after removing (EtO)3P and (EtO)3PO by Kugelrohr distillation
under reduced pressure, the remaining residue was diluted with hot
EtOAc (50 mL). The organic phase was washed with brine (3 × 20 mL)
and dried over MgSO4. Solvent was removed under reduced
pressure, and the remaining residue was purified by flash chromatography
on silica gel (cyclohexane-EtOAc, 20:1).
General Procedure
for the Mo(VI)-Catalyzed Domino Reaction under Microwave Conditions
with Ph3P
as a Reagent
A 10 mL process vial was charged with
a mixture of 7 (1 mmol), Ph3P,
MoO2Cl2(dmf)2, and toluene (3 mL).
The vial was sealed, placed into the cavity of the microwave reactor, and
irradiated with microwaves at 200 ˚C for 30-240
min, after filtration and removal of the solvent the reaction mixture
was poured into H2O (100 mL) and extracted with EtOAc
(3 × 50 mL). The combined organic
phases were washed with brine (3 × 20 mL),
dried over MgSO4, and the solvent was removed under reduced
pressure. The remaining residue was purified by flash chromatography
on silica gel (cyclohexane-EtOAc, 20:1). Alternatively,
the reaction mixture can also be purified by flash column chroma-tography
without any workup procedure.