Topics in Current Chemistry (2019) 377:37
1 3
1 Introduction
Light has been long recognized as an abundant and renewable energy source
that meets the demands of green chemical synthesis. Organic transformations
triggered by visible light are now offering unique synthetic methods that attract
increasing interest from synthetic communities. Except for molecules that can
absorb visible light by themselves, most of the photoinduced redox processes
need the joint use of photosensitizers which absorb visible light and sensitize
organic molecules via an electron/energy transfer process.
The most widely used photosensitizers are polypyridyl complexes of metal
ruthenium and iridium, owing to their thermostability, ease of synthesis, and
excellent photoredox performance. The combination of metal complex photocatalysis and organocatalysis also enables remarkable chemical reactions that are
normally not accessible with either catalyst alone. This article highlights the catalytic asymmetric organic reactions enabled by the combination of organocatalysis
and photoredox catalysis (limited to organometallic photosensitizers).
2 Enamine/Iminium Catalysis
The carbonyl moiety plays a major role in many synthetic modifications and fragment coupling steps. However, the direct asymmetric alkylation of carbonyls
using inexpensive and abundant aldehydes was an enduring challenge in organic
synthesis. To overcome this challenge, the MacMillan group in 2008 developed
an elegant platform for the asymmetric intermolecular α-alkylation of aldehydes
by using a dual photoredox/organocatalyst process [1]. In particular, the new
asymmetric alkylation protocol combines Ru(bpy) 3 Cl 2 photocatalyst (PC-1) and
chiral imidazolidinone catalyst (OC-1) in an interwoven activation fashion to
deliver a variety of enantioenriched α-alkyl aldehyde products (Scheme 1).The
key alkylation step was achieved via the addition of the electron-deficient alkyl
radical to the chiral enamine intermediate.
Organofluorine compounds are valuable chemicals with numerous applications
in dyes, polymers, agrochemicals, and pharmaceuticals owing to their unique
physical properties. In 2009, the MacMillan group utilized their dual photocatalysis/organocatalysis strategy to accomplish the significant enantioselective trifluoromethylation and perfluoroalkylation processes of aldehydes at their α-positions
[2]. The key alkylation step occurs via rapid addition of the trifluoromethyl radical to the enamine intermediate. The reaction proved to be tolerant to sterically
demanding coupling partners without loss of enantiocontrol with high efficiency
(Scheme 2). Interestingly, the obtained α-trifluoromethyl aldehyde could serve
as promising building block for the generation of a variety of organofluorine
synthons.
In 2010, the same group reported an asymmetric alkylation protocol for
α-benzylation of aldehydes by utilizing electron-deficient aryl substrates via the
Reprinted from the journal
68
1 3
1 Introduction
Light has been long recognized as an abundant and renewable energy source
that meets the demands of green chemical synthesis. Organic transformations
triggered by visible light are now offering unique synthetic methods that attract
increasing interest from synthetic communities. Except for molecules that can
absorb visible light by themselves, most of the photoinduced redox processes
need the joint use of photosensitizers which absorb visible light and sensitize
organic molecules via an electron/energy transfer process.
The most widely used photosensitizers are polypyridyl complexes of metal
ruthenium and iridium, owing to their thermostability, ease of synthesis, and
excellent photoredox performance. The combination of metal complex photocatalysis and organocatalysis also enables remarkable chemical reactions that are
normally not accessible with either catalyst alone. This article highlights the catalytic asymmetric organic reactions enabled by the combination of organocatalysis
and photoredox catalysis (limited to organometallic photosensitizers).
2 Enamine/Iminium Catalysis
The carbonyl moiety plays a major role in many synthetic modifications and fragment coupling steps. However, the direct asymmetric alkylation of carbonyls
using inexpensive and abundant aldehydes was an enduring challenge in organic
synthesis. To overcome this challenge, the MacMillan group in 2008 developed
an elegant platform for the asymmetric intermolecular α-alkylation of aldehydes
by using a dual photoredox/organocatalyst process [1]. In particular, the new
asymmetric alkylation protocol combines Ru(bpy) 3 Cl 2 photocatalyst (PC-1) and
chiral imidazolidinone catalyst (OC-1) in an interwoven activation fashion to
deliver a variety of enantioenriched α-alkyl aldehyde products (Scheme 1).The
key alkylation step was achieved via the addition of the electron-deficient alkyl
radical to the chiral enamine intermediate.
Organofluorine compounds are valuable chemicals with numerous applications
in dyes, polymers, agrochemicals, and pharmaceuticals owing to their unique
physical properties. In 2009, the MacMillan group utilized their dual photocatalysis/organocatalysis strategy to accomplish the significant enantioselective trifluoromethylation and perfluoroalkylation processes of aldehydes at their α-positions
[2]. The key alkylation step occurs via rapid addition of the trifluoromethyl radical to the enamine intermediate. The reaction proved to be tolerant to sterically
demanding coupling partners without loss of enantiocontrol with high efficiency
(Scheme 2). Interestingly, the obtained α-trifluoromethyl aldehyde could serve
as promising building block for the generation of a variety of organofluorine
synthons.
In 2010, the same group reported an asymmetric alkylation protocol for
α-benzylation of aldehydes by utilizing electron-deficient aryl substrates via the
Reprinted from the journal
68