Chemistry Reference
In-Depth Information
EtSH (2 equiv),
DBU (
1
) (0.19 equiv)
O
OH
S
O
OH
O
N
Ph
EtS
Ph
DCM, 0 ˚C , 0.5 h
Me
Me
Ph
92%
Scheme 3.37
DBU (1) catalysed removal of chiral auxiliary
3.3.10 Displacement Reaction
DBU (1) was used as a base in the dehydrochlorination/ring closure of chiral chlorohydrins
with high retention of optical purity [60]. N-Acyl-
b
-hydroxy-4-phenyloxazolidinethiones
are rapidly converted into the corresponding ethyl thioesters in high yields by treatment
with ethanethiol (EtSH) in the presence of a catalytic DBU (1) [61] (Scheme 3.37). Thus,
the chiral auxiliary could be removed cleanly and non-destructively.
3.3.11 Horner-Wadsworth-Emmons Reaction
TheWittig reaction of 4-oxopiperidinewith ethoxycarbonyl triphenylphosphoniummethy-
lide either did not occur or conversion was extremely low depending on the reaction
conditions; for example, potassium tert-butoxide (
t
BuOK) (excess). The use of
t
BuOK (2.8
equiv.) gives the best isolation of 15%of the E-derivative after 43 h reflux in toluene. On the
other hand, the Horner-Wadsworth-Emmons (HWE) reaction using excess amounts of
triethyl phosphonoacetate and DBU (1) [or DBN (2)] occurred in the presence of lithium
chloride to give a diastereoisomeric E/Z mixture, in which the E-alkene is predominant and
unexpected epimerization at position 2 in the product caused by possible deprotonation at
position 3 with the organobase followed by ring opening and recyclization is observed [62]
(Scheme 3.38).
3.3.12
Intramolecular Cyclization
Alkylidene phthalides are produced from 5-exo-dig cyclization of o-alkynylbenzoic acids.
However, concomitant generation of isocoumarins via 6-endo-dig cyclization is normally
problematic [63].
Cyclization of o-alkenylbenzoic acid catalysed with organobases affords the phthalide
through 5-exo mode regioselectivity in good to excellent yields [64]. Among the bases
examined, DBU (1) exhibits the highest catalytic activity, 5mol% of 1 is sufficient to
promote completion of the reaction and 1 displays an excellent performance in highly polar
solvents such as MeCN and DMSO (Table 3.4).
3.3.13
Isomerization
DBU (1) effectively works in the isomerization of the condensation products from
L
-
menthonewith salicylamide, which could be a potential chiral 1,3-benzoxazinone auxiliary
[65] (Scheme 3.39).
