C O M M U N I C A T I O N S
Table 2. Reaction Scopea
In summary, we have developed a direct electrophilic amination
of homoenolates catalyzed by N-heterocyclic carbenes. The addition
of a carbene derived from triazolium salt D to an R,â-unsaturated
aldehyde generates a homoenolate intermediate which undergoes
a formal [3+2] cycloaddition with an 1-acyl-2-aryldiazene to afford
pyrazolidinones as a single regioisomer. A chiral triazolium salt
can be used to control the newly formed stereocenter of the product,
which results in good selectivity. The pyrazolidinone products can
be converted into â-amino acid derivatives in excellent yields.
Carbene catalysis continues to facilitate new strategies for the
creation of valuable molecules from simple precursors.
entry
R
Ar
R1
yield (%)b
1
2
3
4
5
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
63 (5)
60 (6)
66 (7)
64 (8)
3-OMe-Ph
2-OMe-Ph
2-Naphthyl
4-Cl-Ph
2-OMe-Ph
Me
61 (9)
6
7
3-Me-Ph
2-Me-Ph
3-Me-Ph
4-Cl-Ph
4-F-Ph
3-Me-Ph
Ph
64 (10)
82 (11)
84 (12)
68 (13)
61 (14)
73 (15)
71 (16)
63 (17)
Acknowledgment. Support for this work was generously
provided by NIGMS (RO1 GM73072), Abbott Laboratories,
Amgen, AstraZeneca, GlaxoSmithKline, 3M, the Sloan Foundation,
and Boehringer-Ingelheim. A.C. thanks Dow Chemical Co. for a
graduate fellowship.
8
9
CH2CH2CH3
Ph
10
11
12
13
Ph
Ph
Ph
Ph
3-Me-Ph
4-Me-Ph
Ph
Supporting Information Available: Experimental procedures and
spectral data for new compounds. This material is available free of
a 3 equiv of 2. b Isolated yields after chromatography.
as the electrophile. On the basis of our carbene-catalyzed hydroa-
cylation studies,5a we postulate that tetrahedral intermediate I
(Scheme 1) can form the desired homoenolate intermediate (path
A) or collapse to afford an acyl heteroazolium species with
concomitant hydride transfer to the diazene (path B). The undesired
reaction reduces 2d to the observed hydrazine and sacrifices an
equivalent of unsaturated aldehyde. Fortunately, by tuning the
structure of the carbene catalyst to D and lowering the reaction
temperature, we can maximize the desired homoenolate amination
(Table 1, entry 11).8
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bond of pyrazolidinone 19 with Raney nickel produces the â-amino
amide 20 in excellent yield (96%).
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