C O M M U N I C A T I O N S
Scheme 1. The Proposed Mechanism
separable mixture of the two diastereoisomers in a combined yield
of 69% (two steps), of which the major diastereoisomer was
obtained as a crystalline solid ([R]D -216.2 (c 0.5, EtOH)). The
X-ray crystal structure determination of this pure diastereoisomer
of 26 unequivocally proved the 4,10-cis-relationship and the 1,10-
trans-configuration.19 Hydrogenation of the pure trans-diastere-
oisomer, followed by hydride reduction, led to the enantiopure key
building block 27 in 88% yield. This eight-step (five catalytic,
starting from (S)-22) synthesis of the amino alcohol 27 - a key
synthon in the synthesis of the poisonous frog alkaloid quinolizidine
233A and derivatives - shows the usefulness of the new Pd-
catalyzed amidation of alkoxyallenes that can be applied to a wide
range of amide substrates. Currently, we are conducting further
research toward application of the N,O-acetals in other types of
reactions and natural product syntheses.
or via external attack to form the product 19 and regenerating Pd-
(0). This would also explain why more vigorous conditions and
longer reaction times are required.
Having established straightforward access to the required N,O-
acetals, we investigated its application in the synthesis of the
1-ethylquinolizidine framework. In doing so, we focused on the
construction of the enantiopure 1-ethylquinolizidine amino alcohol
27 (Scheme 2), because it is known that this intermediate in racemic
form can be elaborated to quinolizidine 233A (1).3c In an analogous
fashion, 1-epi-207I (28) may be prepared from 27.
Acknowledgment. This research has been financially supported
by the Council for Chemical Sciences of the Netherlands Organiza-
tion for Scientific Research (CW-NWO).
Supporting Information Available: Experimental procedures, and
spectroscopic and analytical data (PDF). Crystallograpic data (CIF).
This material is available free of charge via the Internet at http://
pubs.acs.org.
References
Scheme 2. Synthesis of the Enantiopure Key Synthon 27a
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Thus, enantiopure protected 2-amino-6-heptenoic ester15 (22) was
treated with the Hoveyda-Grubbs16a catalyst and allyltrimethyl-
silane (ATMS) to give the desired product in 87% yield via an
unusual double bond isomerization,17 followed by cross-metathesis
with ATMS. Amidopalladation with benzyl propadienyl ether gave
the allylic N,O-acetal 23 in 80% yield. Crucial CC-bond formation
took place by treatment with a catalytic amount of Sn(OTf)2 (2
mol %), leading to fast formation of the desired cyclized target 24
as a mixture of two diastereoisomers. Thiophenolate-mediated
sulfonamide cleavage18 in MeCN at 50 °C afforded the free amine
25 as a 86:14 mixture of trans/cis-isomers. Elaboration to the
desired bicyclic target consisted of amine acylation with 3-butenoyl
chloride, followed by ring-closing metathesis of the triene using
the second-generation Grubbs16b catalyst. This afforded 26 as a
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