Chemistry Reference
In-Depth Information
H
Me
2
N
NMe
2
Me
2
N
NMe
2
Proton Sponge™ (
1
)
(1,8-bis(dimethylamino)naphthalene)
2
Figure 8.1
Structure of Proton Sponge (1)
8.2 Alkylation and Hetero Michael Reaction
8.2.1 Amine Synthesis by
N
-Alkylation
N-Alkylation with an alkylating agent and Proton Sponge (1) has been reported (Scheme
8.1). Reaction of a pyrrolidine derivative and 3-butenyl triflate using Proton Sponge (1)
gave a tertiary amine in 75% yield [3]. N-Methylation of aziridine was conducted using
dimethyl sulfate and Proton Sponge (1) [4].
Dealkylation of a tertiary amine was firstly reported by Olofson et al. [5]. In this
reaction, Ratz et al. reported the effective use of Proton Sponge (1) for carbamate
formation [6]. Thus, the reaction of the tertiary amine with 2,2,2-trichloroethyl chlor-
oformate (ACE-Cl) and Proton Sponge (1), and subsequent hydrolysis of the resulting
carbamate with sodium hydroxide (NaOH) gave amine in 75% yield without loss of optical
purity (Scheme 8.2).
8.2.2 Ether Synthesis by
O
-Alkylation
Several mild and efficient alcohol alkylation (alkoxylation) methods are known, including
the classic Williamson reaction, alkyl halide and silver oxide in combination, and alkyl
triflate and 2,6-di-tert-butyl-4-methylpyridine. However, for sterically hindered or opti-
cally labile alcohols, alternative powerful and mild methodology is required.
Diemet al. reported amild alkoxylation reaction using trialkyloxonium tetrafluoroborate
(Meerwein
s salt) [7]. In this reaction, Proton Sponge (1) was found to be an effective base,
as well as H
unig
s base (diisopropylethylamine) (Table 8.1). The reaction of (R)-(
þ
)-1-
€
phenylethyl alcohol with Meerwein
s trimethyloxonium tetrafluoroborate (2.1 equiv.) and
Proton Sponge (1) (2.1 equiv.) in dichloromethane at room temperature gavemethyl ether in
69% yield without loss of optical purity (Table 8.1, run 1). (S)-(
)-2-Methyl-1-butanol was
also methylated in 57% yield (run 3).
Evans et al. used the same reaction conditions for ether formation in the synthesis of
lonomycinA [8]. The hindered alcohol in a cyclic polyether was efficientlymethylatedwith
trimethyloxonium tetrafluoroborate and Proton Sponge (1) (5 equiv. each, 0
C) to give the
desired ether alongwith 16%recovery of the startingmaterial (Scheme 8.3). In this reaction,
other methylation conditions examined were ineffective, and elevated temperature caused
the decomposition of the starting polyether. De Brabander et al. reported the selective
formation of anisole derivative from phenol usingMeerwein
s salt and Proton Sponge (1)in
combination, without formation of isocoumarin by-products [9,10] (Scheme 8.3).
