Narcissus and Daffodil

322 V.N. Bulavka and O.N. Tolkachev
mixture of E- and Z-forms. On anodic oxidation of the corresponding N-formyl
and N-trifluoroacetyl derivatives 105 and 106 (R= CHO and COCF3 ) in the presence
of MeCN and 2% MeOH, a high rate of conversion of the parent compounds took
place (80–100%), while the main reaction products were isolated as ketals (107 and
108, R = CHO and COCF3 ) and the benzylic methylene group underwent oxidative
methoxylation (Vlahov et al., 1984; Krikorian et al., 1984). The oxidation of amide
102 in MeCN and 33% MeOH resulted in 30% of methoxylated ketal 104, while
in the same conditions amide 98 formed methoxycyclohexadienone 101 (Vlahov
et al., 1984). The electrochemical oxidation reaction was thoroughly studied in
respect of the effects of substituents and reaction conditions on the reaction products
and their yields. It was shown that, owing to the high lability of the spirodienones
produced, they could not be converted to the expected dihydrofuran
derivatives.
Synthesis of alkaloids of the galanthamine group using
hypervalent iodine (III) oxidation agent
Kita et al. (1998) extended the phenol-coupling reaction using a hypervalent
iodine (III) reagent for the synthesis of galanthamine-type Amaryllidaceae alkaloids.
As a result, total syntheses of (±)-sanguinine, (±)-galanthamine, (±)-narwedine,
(±)-lycoramine and (±)-norgalanthamine were accomplished (Figures 12.14, 12.15
and 12.16).
The starting material 3,4-dihydroxybenzoic acid (109), on esterification to
methyl ester 110 (96%), and following protection of hydroxy groups with
diphenyldichloromethane as the cyclic diphenylketal 111 and LiAlH 4 reduction
to the alcohol 112, was brominated with N-bromosuccinimide to afford 113 in
98% yield (over the three stages). The bromoalcohol 113 was then converted
(NaOCH 3 – Me 3 SiOSiMe 3 ) to trimethylsilanyl derivative 114 in 56% yield, which
was oxidised with active MnO 2 to the corresponding aldehyde 115 (86%). Aldehyde
115 with tyramine (17) in methanol formed the Schiff base 116, which on
NaBH 4 reduction to norbelladine derivative 117 and acylation (without isolation
of the latter) with trifluoroacetic anhydride, was converted to amide 118 in 96%
yield (over the three stages). Phenolic oxidation of 118 with phenyliodine (III)
bis(trifluoroacetate) in CF 3 CH 2 OH (–40 °C, N 2 ) led to dienone 119 in 36% yield.
The latter underwent complete de-protection in trifluoroacetic acid medium
to form enone 120 in 100% yield. Methylation with dimethyl sulphate gave
N-demethyl-N-trifluoroacetyl-narwedine 121 in quantitative yield (Kita et al., 1998)
(Figure 12.14).
The same authors used compounds 121 and 120 (without isolation) for the
preparation of alkaloids of the galanthamine group (Figure 12.15). Thus, 121 on
hydrolysis with K 2 CO 3 in aqueous methanol formed N-demethylnarwedine (122),
which, without isolation, was methylated with formaldehyde and formic acid to 2
(100%), reduced with L-Selectride (–78 °C in tetrahydrofuran) to 1 (100%), and,
following hydrogenation over Pd/C, to lycoramine (123) (100%). According to
another route 121 was hydrolysed to 122 and, without isolation, was reduced with
L-Selectride to N-norgalanthamine (44) in 82% yield. Sanguinine was synthesised
as follows: 119 was de-protected and 120, without isolation, afforded 124 in 72%
yield on treatment with imidazole and tertiary butyldimethylsilyl chloride. Reduction