C O M M U N I C A T I O N S
CF3CO2Ag, and AcOAg readily facilitated the rearrangement to
furnish the desired product in excellent yields. The presence of
triethylamine, which is often used in Arndt-Eistert homologations
as an additive, however diminished the yield. As a result of this
study, we selected PhCO2Ag as the catalyst and CH2Cl2 as the
solvent for further studies of this method. With optimized reaction
conditions in hand, we investigated the scope of the reaction (Table
1). First, diazoketones 3, 5, and 7 (entries 1-3) were synthesized
from N-benzylglycine and the corresponding alkynes. Upon treat-
ment with PhCO2Ag, the desired enaminones 4, 6, and 8 were
obtained in good yields. Next, R-substituted diazoketone 9 and 11
(entries 4-5) were prepared from N-methylalanine and N-meth-
ylleucine respectively, which underwent cyclization to afford ꢀ-alkyl
enaminones 10 and 12. 19F NMR analysis of the Mosher ester of
(S)-12 in comparison to the Mosher esters of (()-12 revealed that
only a single diastereoisomer of the (S)-12 Mosher ester had formed
(see Supporting Information (SI)).11 Diazoketones 13, 15, 17, and
19 (entries 6-9) derived from cyclic amino acids afforded bicyclic
enaminones 14, 16, 18, and 20 in good yields. These derivatives
are known to be excellent intermediates for indolizidine, and
quinolizidine syntheses.2 Mosher ester derivatives of 14 and 16
showed single diastereoisomers by HPLC analysis (see SI).11
(2R,8aS)-18 was formed as a single diastereoisomer as determined
Table 1. Substrate Scope of the Reactiona
1
by H NMR.
In summary, we have developed a novel enantiospecific synthetic
method to obtain monocyclic, bicyclic, and tricyclic enaminones
from amino acids in two steps. Due to the lack of racemization, a
simple nucleophilic 6-exo-dig cyclization is a plausible mechanism,
which is a favorable transformation according to Baldwin’s rules.10
Further investigation regarding the synthetic utility of this meth-
odology is ongoing.
Acknowledgment. This work was supported by National
Institutes of Health Grant GM081267 and the University of
Minnesota through the Vince and McKnight Endowed Chairs. We
thank Dr. Subhashree Rangarajan for mass spectrometry assistance.
Supporting Information Available: Experimental procedures and
spectroscopic data for all new compounds (PDF). This material is
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a Reaction conditions: diazoketone and PhCO2Ag (10 mol %) in
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%
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determined by 19F NMR (Mosher ester derivatives); only one isomer
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1
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