pubs.acs.org/joc
very few reports about the aza-MBH reactions of imines with
Beyond the Aza-Morita-Baylis-Hillman Reaction:
Lewis Base-Catalyzed Reactions of N-Boc-imines
with Ethyl 2,3-Butadienoate
allenoates4 providing densely functionalized allenes because
many kinds of imines and 2,3-butadienoates are easy to
obtain via cycloaddition reactions under different Lewis
bases.5-7 For instance, the reactions of N-tosylated imines
and 2,3-butadienoates catalyzed by phosphine to give five-
membered pyrrolidine derivatives (Scheme 1, eq 1) have been
reported by Lu.5 For the same reaction, we previously
reported that different heterocyclic products such as azeti-
dine or dihydropyridine derivatives could be formed in the
presence of 1,4-diazabicyclo[2.2.2]octane (DABCO) or N,N-
4-dimethylaminopyridine (DMAP), respectively (Scheme 1,
eqs 2 and 3).7
Xiao-Yang Guan, Yin Wei,* and Min Shi*
State Key Laboratory of Organometallic Chemistry,
Shanghai Institute of Organic Chemistry, Chinese Academy
of Sciences, 354 Fenglin Road, Shanghai 200032, China
weiyin@mail.sioc.ac.cn; mshi@mail.sioc.ac.cn
Received April 29, 2009
Lu has also reported that the normal aza-MBH adducts
could be formed in moderate yield in the PPh3-catalyzed
reaction between methyl 2,3-butadienoate and N-(etho-
xycarbonyl)benzaldimine instead of N-sulfonylimines
(Scheme 2, eq 1).5b Our DABCO-catalyzed reactions of
N-tosylated imines with ethyl 2,3-butadienoate only afford
trace normal aza-MBH adducts (Scheme 2, eq 2).7b These
results showed that the reactivities of both imines and
catalysts influence the final products from the same starting
materials.
In this paper, we report the different reactivity patterns
shown by nitrogen- and phosphorus-containing Lewis bases
as catalysts in the reactions of N-Boc-imines with ethyl 2,3-
butadienoate, which are different from the previous observa-
tions in the normal aza-MBH reactions of other imines and
beyond the scope of the aza-MBH reactions.
The potential of several commonly used nitrogen-contain-
ing Lewis bases as catalysts has been assessed for the aza-
MBH reaction of ethyl 2,3-butadienoate with N-Boc-imine
1a. The results are summarized in Table 1. Notably, DABCO
and pyridine are more efficient than other nitrogen-contain-
ing Lewis bases for catalysis of this reaction. As can be seen
in Table 1, DABCO shows an excellent catalytic activity for
the reaction of 1a with ethyl 2,3-butadienoate in tetrahy-
drofuran (THF), affording product 2a in 95% yield. Pyridine
also proved as a good catalyst, forming 2a in 66% yield
(Table 1, entry 2). However, other nitrogen-containing
Lewis bases N,N-4-dimethylaminopyridine (DMAP) and
1,8-diazabicyclo[5.4.0]-7-undecene (DBU) gave poor yields,
Lewis base catalyzed reactions of N-Boc-imines and ethyl
2,3-butadienoate were investigated systematically. The
normal aza-Morita-Bylis-Hillman products were ob-
tained in good to excellent yields catalyzed by DABCO.
When PPh3 was used as the catalyst, novel rearrangement
product (E)-ethyl 2-((Z)-(tert-butoxycarbonylimino)-
(aryl)methyl)but-2-enoates could be formed in moderate
yields.
The use of imines as electrophiles in the Morita-Baylis-
Hillman reactions,1 commonly referred to as the aza-
Morita-Baylis-Hillman (aza-MBH) reaction,2 is extremely
fascinating because of the great potential of its products for
further transformation and its superior mild reaction con-
ditions.3 An extension of the aza-MBH reaction comes
through variation in the structure of the R,β-unsaturated
carbonyl compounds such as allenoates. However, there are
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(4) During preparation of this manuscript, Miller published a commu-
nication about pyridylalanine (Pal)-peptide catalyzed enantioselective al-
lenoate additions to N-acylimines. Cowen, B. J; Saunders, L. B; Miller, S. J.
J. Am. Chem. Soc. 2009, 131, 6105–6107.
DOI: 10.1021/jo9008832
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Published on Web 07/22/2009
J. Org. Chem. 2009, 74, 6343–6346 6343
2009 American Chemical Society