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Journal of the American Chemical Society
Stern-Volmer quenching studies of this system show the
synthetic utility of this transformation is highlighted
through an expedient enantioselective synthesis of in-
dolizidine alkaloid monomorine I.
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carbamate efficiently quenches the excited state of the
acridinium photocatalyst (Chart 2D). In the absence of
carbamate, the excited state lifetime of catalyst 1 was
measured to be 14.9 ns, incrementally increasing the car-
bamate concentration to 20 mM gave a steady decrease in
excited state lifetime to 6.3 ns (see SI for details).This re-
sult shows that the requisite carbamyl cation radicals may
be generated under the reaction conditions. The photo-
ASSOCIATED CONTENT
Supporting Information
The Supporting Information is available free of charge on the
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chemical quantum yield (Φ ) of the reaction between N-
r
Boc-piperidine and methyl vinyl ketone to form com-
1
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0
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pound 2 was determined to be 0.19±0.03 % (N =2, see SI
AUTHOR INFORMATION
Corresponding Author
1
5
for details) with a quenching fraction (Q) of 0.87. Fur-
thermore, the low quantum yield and efficient quenching
indicate that back electron transfer between the generat-
ed cation radical and the reduced form of the catalyst is a
very efficient process which is in competition with for-
mation of the desired product. While these values support
the proposed mechanism, a slow, yet productive, chain
mechanism cannot be completely ruled out.
*
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENT
This manuscript is dedicated to the Department of Chemis-
try at the University of North Carolina at Chapel Hill, in
Lastly, we sought to probe the stereoselectivity of this
reaction through the introduction of substituents on the
piperidine core (Scheme 1A). Using 4-methyl N-Boc-
piperidine as the substrate afforded 28 in high diasterose-
lectivity (>20:1). The stereochemical outcome of the reac-
tion can be rationalized as proceeding through a pseudo-
half-chair conformation of the radical intermediate akin
to a Fürst-Plattner-type transition state for the rationali-
th
acknowledgement of its 200 anniversary, 1818-2018. We are
grateful for support from Eli Lilly (Eli Lilly Grantee Award to
D.A.N.). This research made use of instrumentation
(
Hewlett–Packard 8453 Chemstation absorption spectrome-
ter) funded by the UNC EFRC: Center for Solar Fuels, an En-
ergy Frontier Research Center supported by the U.S. De-
partment of Energy, Office of Science, Office of Basic Energy
Sciences (DE-SC0001011). The authors would additionally like
to thank Cole Cruz for his assistance in collecting spectro-
scopic data.
16
zation of stereocontrol in cyclohexene-type systems.
Diastereoselectivity is ultimately controlled via a chair-
like transition state (product development control).
When enantioenriched 2-methyl N-Boc-piperidine is re-
acted with methyl vinyl ketone, 29 is formed as a single
regioisomer in high diastereoselectivity (>10:1) with min-
imal erosion of the C5-methyl stereocenter (see SI). A
similar model also predicts the stereochemical outcome
of this transformation. The 2-methyl group occupies the
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1
,3
pseudo-axial position to minimize A interactions with
1
7,18
the equatorial carbamate group.
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of these transformations parallels the selectivity observed
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(
Scheme 1B). The three-step synthesis began with the
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amination sequence to afford the natural product in 51%
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In conclusion, we have developed conditions to selective-
ly alkylate carbamates to afford elaborate secondary
amines with easily removable protecting groups in up to
quantitative yield. Using a photochemical flow reactor,
this transformation is easily scalable with comparable
yields to the analogous batch reactions. Furthermore, the
(
(
(
7
2
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