Chemistry Reference
In-Depth Information
4.2.3.3. Synthesis of Furan and Pyran Heterocycles
Synthesis of heterocycles such as
chiral dihydrobenzopyrans and dihydrobenzofurans can be achieved via intramolecular
C-H insertion of aryldiazoacetates [66]. This approach is an attractive route toward
these compounds.
McKervey and coworkers studied intramolecular C-H activation in
- diazoketone
systems
88
(Table 4.11) to construct chromanone derivatives
89
[128] . Many dirhodium(II)
and copper(I) complexes were tested in this chemistry, but only dirhodium(II) prolinate
complex Rh
2
(
S
- BSP)
4
was found to be effective [128]. The products were formed in
excellent yields (90-98%) and in 33-82% ee. When R
α
was a vinyl or phenyl group, the
enantiomeric excess dropped signifi cantly (50-62% ee). In the case where R = H, the
major diastereomer was the
syn
-product but the diastereoselectivity was only moderate
to good (50-88% de). C-H insertion at a methylene site gave higher enantiomeric excess
(82% ee) than insertion at a methine site (70% ee) [128].
Intramolecular C -H insertions of
ortho
-alkoxy aryldiazoacetates were studied inde-
pendently by Davies et al. [195] and Hashimoto et al. [125]. The most important results
are summarized in Table 4.12. The dirhodium(II) prolinate complex Rh
2
(
S
- DOSP)
4
emerged as the most effective catalyst for insertion into tertiary sites and afforded prod-
ucts
91a - b
in 90-94% yield and 93-98% ee under the appropriate conditions [195]. The
cyclohexyl analogue
90b
, however, gave only 12% yield of the desired product under
the same conditions. Carbene dimerization products were prevalent in this case [195].
The reaction of
90a
catalyzed by Rh
2
(
S
- PTTL)
4
gave only 22% ee [125]. For insertion
into methylene sites, Rh
2
(
S
- PTTL)
4
was by far the most effective catalyst. In system
90d
,
Rh
2
(
S
- DOSP)
4
gave only 63% ee, whereas Rh
2
(
S
- PTTL)
4
gave excellent enantiomeric
excess (94-97% ee) under appropriate conditions [125,195]. Furthermore, moderate to
good yields were obtained with this catalyst (63-91%) as well as good to excellent dia-
stereoselectivities (72 to
′
98% de ). The related Rh
2
(
S
- PTAD)
4
afforded 79% yield for
the benzylic insertion in 95% ee and
>
98% de [127] .
The formation of dihydrobenzofurans has been shown to be an applicable technology
in total synthesis [196,197]. The key step in the total synthesis of (
>
) - ephedradine A (
94
,
Scheme 4.18) is the formation of
trans
- 2 - aryl - 2,3 - dihydrobenzofuran - 3 - carboxylic acid
ester
93
, which was synthesized from
92
via an Rh
2
(
S
- DOSP)
4
- catalyzed, diastereoselec-
tive intramolecular C-H insertion. Only 0.3 mol % catalyst was employed to effect the
transformation in 63% yield with 86% de [196,197] .
−
TABLE 4.11. Synthesis of Chromanone Derivatives
R
R'
R
'
O
O
Rh
2
(
S
-BSP)
4
N
2
R
CH
2
Cl
2
, 40°C
Me
Me
O
O
8
8
8
Compound
R =
R
′
=
Yield (%)
de (%)
ee (%)
a
H
M e
> 98
50 - 78
82
b
Me
Me
> 98
—
70
a
a
Reaction at 0 ° C.
