Chemistry Reference
In-Depth Information
the C19-C20 olefin was troublesome under the regular Wittig reaction conditions, that is,
n-Bu
3
P-LDA, n-Bu
3
P-LHMDS, Et
3
P-
t
BuOK, nor was the Horner-Wadsworth-Emmons
(HWE) olefination protocol effective. Since the bromide 66 has an electron-deficient
heteroaromatic moiety, Et
3
P-DBU in DMF at 0
C was employed, and 67 obtained as a
single olefin isomer in 86% yield [16] (Scheme 7.13). This advanced intermediate was
converted to 68 through the Yamaguchi-Yonemitsu macrolactonization.
The intramolecular HWE reaction in the presence ofDBUwas employed for the synthesis
of (
)-rhizoxin D (71) by Jiang et al. [17]. Reaction of the aldehyde 69 with DBU-LiCl
(Masamune-Roush conditions) [18] in acetonitrile at room temperature under high dilution
conditions constructed the C2
รพ
C3 bond to form the macrolactone 70 (Scheme 7.14).
Further elongation of the C20
C21 bond achieved the total synthesis of 71.
A guanidine base has also been used for intramolecular HWE reaction. Nicolaou et al.
reported a synthetic study of the originally proposed structure of diazonamide A (74)[19],
employing the modifiedMasamune-Roush conditions [18]. Thus, reaction of aldehyde 72 with
TMG (3)-LiCl in DMF at 70
C generated 73 as a single atropisomer in 55-60% yield. Under
other reaction conditions, for example, LHMDS in THF or DBU-LiCl in acetonitrile, 73 was
obtained in only 0
35%yield (Scheme 7.15). Unfortunately, this advanced intermediate could
not be transformed to the final product 74, because the C29-30 olefin was resistant to oxidation.
Enamide ester, which is a useful synthetic intermediate for a variety of
-amino acids, can
be prepared by means of the HWE reaction in the presence of TMG (3) or DBU [20,21]. In
the synthesis of teicoplanin aglycon (80) reported by Evans et al. [22], one of the
phenylalanine derivatives 79 was synthesized from the aldehyde 75. HWE reaction of
aldehyde 75 with phosphonate 76 using TMG (3) in THF gave (Z)-enamide ester 77 in 99%
yield. Asymmetric hydrogenation of 77 catalysed by rhodium(I) complex 78 (1mol%) gave
the phenylalanine ester 79 in 96% with 94% ee (Scheme 7.16).
Since the above methodology provides easy access to a variety of
a
-amino acid
derivatives, many applications for the synthesis of natural products have been reported
[23-25]. The HWE reaction of the sterically hindered aldehyde 81 with phosphonate 82
using TMG (3) proceeded to give (Z)-enamide 83 in 80% yield from the alcohol (2-step
yield) [26]. The resulting enamide 83 was submitted to the asymmetric hydrogenation
reaction using Burk
a
s rhodium(I) catalyst [27] to give 84 in 85% yield as the sole product
(Scheme 7.17). The
a
-amino acid ester 84 was successfully converted to neodysiherbaine
A(85).
Davis et al. reported synthetic studies of martefragin A (91) [28]. For the construction of
the asymmetric centre next to the oxazole, HWE reaction of the aldehyde and subsequent
asymmetric hydrogenation were applied. The HWE reaction of chiral aldehyde 86 with
phosphonate 87 in the presence of DBU gave (Z)-enamide ester 88, although epimeriza-
tion was observed (75% ee). When the reaction was conducted using TMG (3),
epimerization was suppressed (95% ee). Enamide ester was converted to the potential
precursor 90 for 91 through the
a
-amino acid ester 89 via asymmetric hydrogenation
(Scheme 7.18).
Enamide ester synthesis was applied for the synthesis of a complex indole natural product
by Okano et al. [29]. (Z)-Enamide ester 94 was obtained by HWE reaction of aldehyde 92
with phosphonate 93 in the presence of TMG (3), in 84% yield. Treatment of the resulting
ester with copper iodide (CuI) and CsOAc provided dihydropyrroloindole 95, which was
efficiently converted to yatakemycin (96) (Scheme 7.NaN).
