Organic Letters
Letter
developed, thus providing a useful platform for constructing
structural diversity (Scheme 1, a). In addition, Melchiorre,16
Scheme2, the hydroacylation method was tested with different
types of unsaturated CC bond compounds. Styrene with
Scheme 1. Visible-Light-Promoted Synthetic Strategies
Based on the Use of DHPs as Radical Precursors
Scheme 2. Investigation on the Alkene Scope of the
Hydroacylation.
a
Molander,17 Cheng,18 and Meggers,19 respectively, docu-
mented the photocatalytic radical addition of alkyl-DHPs
across CC to form new Csp3−Csp2 bonds (Scheme 1, b).
Nevertheless, in sharp contrast, such a mode to release acyl
radicals had not been revealed until the Melchiorre group
attributed it to the photo-/organocatalytic synthesis of 1,4-
dicarbonyl compounds in strong acid conditions, in which an
acyl radical could be easily obtained from the photoactivated
acyl-DHPs and engaged in an enantioselectively conjugated
addition to enals to afford the desired products (Scheme 1,
c).20 Motivated by the above research background, we
wondered if the carbon radical intermediates generated from
acyl radical addition to CC bond might be quenched by a
hydrogen atom absorption or radical interception process to
achieve the functionalization of alkenes. Herein, we describe a
visible-light-promoted strategy that facilitates the alkene
hydroacylationin the absence of photocatalyst and a NiCl2·
DME-mediated diacylation by using DHPs as acyl radical
precursors (Scheme 1, d). Notably, the developed method-
ology was proved applicable to both electron-rich and electron-
poor alkenes and featured broad substrate scope and good
functional group tolerance. Its potential application was
demonstrated by scalable experiment and expedient prepara-
tion of complex natural product/drug based ketones.
The initial investigation was carried out by using styrene and
4-benzoyl-DHPs as model substrates under the irradiation of
36 W blue LEDs. In the presence of Eosin Y, we delightfully
observed the formation of alkene hydroacylation product 1
with 17% isolation yield within 10 h under N2 atmosphere in
MeCN. Sets of photocatalysts with different natures were then
evaluated,which displayed a similar effect on the reaction
result. Next, we conducted the reaction without any photo-
catalyst and surprisingly found this protocol was still feasible,
providing 1 in 26% yield. Subsequent extensive investigation
on base disclosed 2.0 equiv of Cs2CO3 as a key and effective
additive, dramatically improving the yield of 1 to 87%. After a
series of screenings on solvents, MeCN was found to be the
optimal medium. In addition, treatment of the reaction system
under air atmosphere resulted in a sharp decrease in yield,
which might be due to the radical quenching effect of oxygen
molecules. Moreover, no reaction occurred in the absence of
light irradiation, which strongly confirmed the visible-light-
promoted property of this developed protocol. (For details of
a
Standard conditions: alkene (0.2 mmol), DHPs (0.3 mmol), Cs2CO3
(0.4 mmol), MeCN (2 mL), N2 atmosphere, blue LED irradiation for
10 h. Reaction conducted on 15 mmol.
b
either electron-withdrawing or electron-donating substituents
on the phenyl ring reacted smoothly with 4-benzoyl-DHPs,
providing the corresponding products in moderate to high
yields (1−14). Various functional groups, such as alkoxyl (2),
phenyl (3), alkyl (4, 5) and halides (6−10), were well
tolerated despite the substitution patterns. Notably, the
practical potential of this developed method was corroborated
by the scale-up experiment of styrene, which only required 48
h of irradiation to afford desired 1 in 91% isolation yield. In
addition, many synthetically important and/or potentially
reactive groups, like ester (11), amine (12, 13), even the free
alcohol (14), were well matched with the mild conditions.
Hydroacylation products 15−18, which, respectively, derived
from heteroatom-containing and polycyclic aromatic alkenes,
were obtained in good to excellent yields (69%, 96%, 87%, and
84%). Subsequently, the reaction scope was examined with
various gem-disubstituted alkenes. Remarkably, alkenes with a
chain/cyclic alkyl or phenyl on the α-position of CC bonds
were proved to be suitable substrates, affording the desired
products in yields from 50% to 87% (19−23). Additionally,
the transformations proceeded smoothly with benzo(heter)-
cyclic derivatives to give the target hydroacylation products
(24−26). In addition, nonterminal alkenes were compatible
with this synthetic strategy with high regioselectivity (27 and
Having identified the optimal conditions, the reaction scope
with respect to alkenes was next explored. As listed in
B
Org. Lett. XXXX, XXX, XXX−XXX