Synthesis of
g
-Oxo-
a
-amino Acids via Radical Acylation with Car-
boxylic Acids
Kay Merkens,
‡
Francisco José Aguilar Troyano,
‡
Khadijah Anwar, Adrián Gómez-Suárez*
Organic Chemistry, Bergische Universität Wuppertal, Gaußstr. 20, 42119 Wuppertal (Germany)
KEYWORDS: amino acids, photoredox catalysis, acylation, phosphine, radical.
ABSTRACT: Herein we present a highly efficient, light-mediated, deoxygenative protocol to access g-oxo-a-amino acid derivatives.
This radical methodology employs photoredox catalysis, in combination with triphenylphosphine, to generate acyl radicals from
readily available (hetero)aromatic and vinylic carboxylic acids. This approach allows for the straightforward synthesis of g-oxo-a-
amino acids bearing a wide range of functional groups (e.g. Cl, CN, furan, thiophene, Bpin) in synthetically useful yields (~ 60%
average yield). To further highlight the utility of the methodology, several deprotection and derivatization reactions were carried out.
g-Oxo-a-amino acids are highly versatile building blocks in
organic synthesis, as well as key components in biologically ac-
tive molecules. They can be used as precursors for homophenyl-
alanine derivatives,
1
g-hydroxy-a-amino acids,
2
g-valerolac-
tones
3
or g-valerolactames, for example. As it is often the case
in synthetic chemistry, one of the main challenges associated
with this interesting class of amino acids is their stereoselective
synthesis. There are three main retrosynthetic pathways to
achieve this goal: a) via acylation reactions, starting from L-or
D-aspartic acid,
4
b) via asymmetric or diastereoselective Man-
nich reactions,
5
or c) via asymmetric Stetter reactions (Scheme
1A).
6
While powerful, these methodologies present limitations
regarding the scope of nucleophiles, or require the use of chiral
catalysts.
Radical chemistry offers exciting and highly attractive ap-
proaches to access new chemical space in a rapid fashion.
7
As
such, it has been exploited for the synthesis and derivatization
of amino acids and peptides.
8
We recently contributed to this
area with the development of a decarboxylative protocol for the
diastereoselective synthesis of a wide range of unnatural amino
acids (UAAs) using the Beckwith-Karady alkene I
9
as radical
acceptor.
10
Although this methodology granted access to g-oxo-
a-amino acids derivatives (II) when using a-keto acids as ac-
ylating reagents (Scheme 1B), it afforded diminished yields
with electron deficient or (hetero)aromatic systems. In addition,
a-keto acids are not readily available and their synthesis often
requires the use of hazardous reagents, such SeO
2
. Since II is a
highly versatile species, we became interested in developing al-
ternative methodologies for its synthesis using more readily
available starting materials.
Recently, the development of deoxygenative radical strategies
to access acyl radicals has attracted increased attention.
11
Sem-
inal independent studies by Rovis and Doyle,
11e
and Zhu
11d
de-
scribed the use photoredox catalysis to generate phosphine rad-
ical cations that swiftly react with carboxylates to generate acyl
radicals and phosphine oxide after b-scission (vide infra).
12
En-
couraged by these reports, we envisioned that it might be pos-
sible to develop a diastereoselective synthesis of g-oxo-a-amino
acids using I and readily available carboxylic acids as acyl rad-
ical sources (Scheme 1C).
Herein we present a highly efficient, light-mediated deoxygen-
ative protocol to access products II from readily and commer-
cially available (hetero)aromatic and vinylic carboxylic acids.
Figure 1. Synthetic strategies towards g-oxo-a-amino acids
γ-oxo-α-amino acids – versatile building blocks in organic synthesis
A
NH
2
OH
O
O
Asymmetric
Stetter
Friedel-Crafts
Weinreb amide
NH
2
N
H
OH
O
O
OH
OH
O
OH
N
HN
O
O
Nikkomycins
HN
OH
Ph
HO
O
10
CERT-dependent
ceramide trafficking
HPA-12 inhibitor
Main synthetic routes Biologically active compounds
limited coupling
partners
requieres chiral
catalysts
Mannich
N
O
O
Cbz
t
Bu
OH
O
+
N
O
O
O
Cbz
t
Bu
PC
PR
3
O
O
P
O
– OPR
3
Deoxygenative synthesis of γ-oxo-α-amino acids – This work
C
Abundant starting materials+ No chiral catalyst+ (hetero)aromatic & vinylic
carboxylic acids
+
Decarboxylative synthesis of γ-oxo-α-amino acids – previous work
B
N
O
O
Cbz
t
Bu
OH
O
+
N
O
O
O
Cbz
t
Bu
PC
O
α-keto acids – not readily available; prepared using toxic oxidants–
low yields with electron poor substituents–
I II
III
In addition, the utility of this methodology is further highlighted
by several derivatizations and deprotections of product II.
Initial optimisation studies were carried out using benzoic
acid as the acylating reagent.
13
The targeted product (1) could
be isolated in 95% yield and excellent diastereoselectivity (d.r.
>20:1) using 1.0 equiv. of I, 1.5 equiv. of benzoic acid, 1.8
equiv. of PPh
3
, 2.0 equiv. of 2,4,6-collidine and 1.0 mol%
[Ir(dFCF
3
ppy)
2
(dtbbpy)][PF
6
] (Ir-F) in 1,4-dioxane (0.2 M)
while irradiating with 32W blue LEDs (l
max
= 440 nm) for 24 h
at room temperature. Control experiments showed that the re-
action needs both light and a photocatalyst to proceed, and that
the reaction does not proceed when using 4CzIPN,
14
an organ-
ophotocatalyst possessing similar redox potentials to Ir-F.
With the optimized conditions in hand, the scope and limita-
tions, as well as the scalability of the methodology, were ex-
plored (Scheme 1). The standard reaction with benzoic acid was
scaled up to 5.0 mmol (1.4 g of II), affording 1 in 95% (1.9 g)
and 73% (1.4 g) yield using 0.5 mol% and 0.25 mol% of Ir-F,
respectively. This highlights the high catalytic efficiency of the
methodology, affording TON up to 288. Regarding the scope,
aromatic carboxylic acids were first tested (2-15). Both electron
rich and poor para-substituents on the aromatic ring were toler-
ated (2-10), although the latter afforded diminished yields.
However, this represents a significant improvement compared
to our previous methodology employing a-keto acids as acylat-
ing reagents, e.g. compound 9 was isolated in 61% yield vs 31%
yield using a-keto acids.
10
Free nucleophilic motifs, such as
hydroxy groups, were not tolerated (2), however this limitation
could be circumvented by the use of protecting groups (3 and
4). Challenging substrates bearing sensitive functional groups,
such as nitriles (8) or aldehydes (10) afforded the desired prod-
ucts in moderate to poor yields, while compound 15, bearing a
meta-boronic ester substituent, was obtained in 76% yield.
Gratifyingly, ortho-substituents were well tolerated (12 and
13), and salicylic acid derived 13 was obtained in an excellent
92% yield. More complex aromatic carboxylic acids bearing
multiple functional groups (14), afforded the targeted g-oxo-a-
amino acid derivative in excellent yield.
Scheme 1. Scope & limitations of the methodology
Reaction conditions: Acid (0.75 mmol, 1.5 equiv.), I (0.50 mmol, 1.0 equiv.), Ir-F (1.0 mol%), 2,4,6-collidine (0.9 mmol, 1.8 equiv.), 1,4-
dioxane (0.2 M), RT, 24 h;
[a]
5.0 mmol scale, Ir-F 0.5 mol%;
[b]
5.0 mmol scale, Ir-F 0.25 mol%, 72 h;
[c]
48 h;
[d]
DMF (0.2 M); unless
otherwise noted d.r. > 20:1.
N
O
O
O
Cbz
t
Bu
O
O
N
O
O
O
Cbz
t
Bu
Cl
N
O
O
O
Cbz
t
Bu
B
N
O
O
O
Cbz
t
Bu
N
O
O
O
Cbz
t
Bu
BocHN
N
O
O
O
Cbz
t
Bu
N
O
O
O
Cbz
t
Bu
F
N
O
O
O
Cbz
t
Bu
O
H
5 80%
12 95%
15 76%
11 95%
7 61%
10 10%
4 80%
N
O
O
Cbz
t
Bu
OH
O
+
N
O
O
O
Cbz
t
Bu
1,4-dioxane (0.2 M)
Blue LEDs (λ
max
= 440 nm)
RT, 24 h
Ir-F (1.0 mol%)
Collidine (2.0 equiv.)
PPh
3
(1.8 equiv.)
(Heter)aromatic carboxylic acids
N
O
O
O
Cbz
t
Bu
N
N
O
O
O
Cbz
t
Bu
N
N
N
16 45%
Vinylic carboxylic acids
N
O
O
O
Cbz
t
Bu
23 35%
N
O
O
O
Cbz
t
Bu
N
N
O
O
O
Cbz
t
Bu
O
N
O
O
O
Cbz
t
Bu
O
N
O
O
O
Cbz
t
Bu
O
24 48% 25 0% 26 68% 27 31%
[c]
N
N
Ir
N
N
CF
3
F
t
Bu
CF
3
F
F
t
Bu
PF
6
Ir-F
X
N
O
O
O
Cbz
t
Bu
9 61%
[c]
F
3
C
N
O
O
O
Cbz
t
Bu
Br
6 74%
N
O
O
O
Cbz
t
Bu
X
3 X = OMe, 92%
O
N
O
O
Cbz
t
Bu
N
O
N
F
14 87%
1 97% (1.9 g)
[a]
N
O
O
O
Cbz
t
Bu
OAc
13 92%
N
O
O
O
Cbz
t
Bu
NC
8 35%
[c]
(1.0 equiv)(1.5 equiv)
Boc
17 X = H, 39%
[c][d]
17' X = Cl, 18%
[c][d]
2 X = OH, traces
N
O
O
O
Cbz
t
Bu
N
X
O
O
F
23 examples
~ 60% average yield
18 X = CH, 0%
19 X = N, 0%
73% (1.4 g)
[b]
N
O
O
O
Cbz
t
Bu
20 X = NH, 20%
[c]
21 X = O, 58%
22 X = S, 71%
X
The use of heteroaromatic carboxylic acids was also investi-
gated (16-23). While nicotinic acid afforded the desired product
in moderate yields (16), no product was observed with picolinic
or pyrazinoic acids (18-19). Surprisingly, when the reaction was
carried out using 4-chloro-1,3-dimethylpyrazolo[3,4-b]pyri-
dine-5-carboxylic acid, the main product was the dechlorinated
species 17 (39%), while the expected product 17’ was isolated
in 18% yield. The use of 5-membered heterocycles (20-22),
such as unprotected pyrroles (20), furans (21) and thiophenes
(22) afforded the desired products in variable yields (21-71%).
Overall, our new methodology presents a broad functional
group tolerance, where compounds bearing several vectors for
further functionalization, such as halides, boronic esters or
amines, can be readily obtained.
To further challenge the limits of our methodology, the use of
aliphatic, cinnamic and vinylic carboxylic acids as acylating re-
agents was evaluated. While hydrocinnamic acid failed to af-
ford the desired product,
13
cinnamic acid delivered a complex
mixture, from where the targeted product could not be iso-
lated.
15
However, the use of cyclic, vinylic carboxylic acids af-
forded interesting g-oxo-a-amino acid derivatives bearing 5-
and 6-membered heterocycles, such dihydrofuranes (24), tetra-
hydropyrines (26), and tetrahydropyrans (27). To the best of our
knowledge, this is the first time that vinylic carboxylic acids
have been directly used as acyl radical precursors.
To highlight the utility of our methodology, a series of deri-
vatization reactions were carried out. Acidic deprotection of II
using concentrated HCl in 1,4-dioxane, afforded g-oxo-a-
amino acid salts 28-30 in quantitative yields (Scheme 2A).
Moreover, by exploiting the carbonyl motif in II to access the
Scheme 2. Deprotection & derivatisation reactions
corresponding enolate, it was possible to access g-oxo-b-me-
thyl-a-amino acid derivatives (31-33) in good yields and dia-
stereoselectivities (Scheme 2B). Moreover, this methodology
can also be applied for the acylation of dehydroalanine deriva-
tive IA, affording the corresponding product 1A in 55% yield
(Scheme 2C).
Finally, a plausible reaction mechanism for this transfor-
mation is shown in Figure 2. First, the excited photocatalyst
(*Ir
III
, *E
1/2
= +1.21 V versus SCE)
16
undergoes reductive
quenching by PPh
3
(E1/2 = +0.98 V versus SCE)
17
to generate
triphenhylphosphine radical cation III and a Ir
II
species. III re-
acts with the corresponding carboxylic acid to afford phospho-
ranyl radical IV, which readily undergoes b-scission to deliver
OPPh
3
and the key acyl radical V. Subsequent radical addition
of the latter to I affords a-amino radical VI, which after reduc-
tion by the reduced Ir
II
(E
1/2
= −1.37 V vs SCE)
16
and protona-
tion delivers the desired product II. This mechanism is in ac-
cordance with previous proposals for acylation reactions using
photoredox catalysis to access phosphoranyl radicals.
11-12
Quan-
tum yield determinations suggest that there is also a significant
contribution from a radical-chain pathway (F = 13.5).
13
Based
on further experiments, 2,4,6-collidine seems to play a crucial
role in the chain process. However, at this point, the nature of
the chain carrier remains elusive.
13
Figure 2. Plausible reaction mechanism
In conclusion, we have developed a highly efficient, light-me-
diated, deoxygenative strategy for the synthesis of g-oxo-a-
amino acid derivatives. This radical methodology exploits the
addition of acyl radicals, generated from readily available car-
boxylic acids, to Beckwith-Karady alkene I, allowing for the
straightforward synthesis of a wide range of g-oxo-a-amino
acid derivatives in excellent diastereoselectivities and syntheti-
cally useful yields (~ 60% average yield). Furthermore, the syn-
thetic utility of this protocol was highlighted by a series of deri-
vatization reactions, granting access to g-oxo-b -methyl-a-
amino acids in good yields and diastereoselectivities.
ASSOCIATED CONTENT
Supporting Information
The Supporting Information is available free of charge on the ACS
Publications website.
Experimental procedures & characterization data (PDF)
AUTHOR INFORMATION
Corresponding Author
N
O
O
Cbz
t
Bu
O
NH
2
HCl
OH
O
O
Deprotection of II under acidic conditions
A
N
O
O
O
Cbz
t
Bu
1,4-dioxane, 80° C, 2 h
conc. HCl
NH
2
HCl
OH
O
O
OH
NH
2
HCl
OH
O
O
Cl
NH
2
HCl
OH
O
O
28 97% 29 98% 30 95%
Derivatisation of II – access to
γ
-oxo-
β
-methyl-
α
-amino acid derivartives
B
N
O
O
O
Cbz
t
Bu
THF, -78° C to reflux
KN(SiMe
3
)
2
(1.5 equiv.)
MeI (5.0 equiv.)
N
O
O
O
Cbz
t
Bu
N
O
O
Cbz
t
Bu
O
MeO
N
O
O
Cbz
t
Bu
O
32 51% (d.r. 7.5:1) 33 50% (d.r. 12:1)31 44% (d.r. 11:1)
F
Br
Acylation of dehydroalanine derivative IA
C
NBoc
2
OMe
O
Ph
OH
O
+
NBoc
2
OMe
Ph
O
O
DMF (0.2 M)
Blue LEDs (λ
max
= 440 nm)
RT, 24 h
Ir-F (1.0 mol%)
Collidine (2.0 equiv.)
PPh
3
(1.8 equiv.)
(1.0 equiv)(1.5 equiv)
IA
1A 55%
+ H
+
*Ir
III
Ir
III
Ir
II
SET
Ph
P
Ph
Ph
Ph
P
Ph
Ph
Ph
P
Ph
Ph
O
O
– H
+
– OPPh
3
β
-scission
OH
O
O
N
O
O
O
Cbz
t
Bu
N
O
O
Cbz
t
Bu
N
O
O
O
Cbz
t
Bu
I
II
III IV
VVI
* gomezsuarez@uni-wuppertal.de
Author Contributions
‡These authors contributed equally.
Funding Sources
Funded by the Deutsche Forschungsgemeinschaft (DFG, German
Research Foundation) – 443074366
ACKNOWLEDGMENT
This work was supported by the Fonds der Chemischen Industrie
(Liebig fellowship to A.G.S. and Ph.D. scholarship to F.J.A.T.), by
the Deutsche Forschungsgemeinschaft (DFG, German Research
Foundation) – 443074366, and the Bergische Universität Wupper-
tal. We thank Dr Lisa Candish and Jun. Prof. Matthew N. Hopkin-
son for fruitful discussions and proof reading of the manuscript.
Umicore A.G. is acknowledged for its generous donation of mate-
rials. Prof. Stefan Kirsch (BUW) is greatly acknowledged for his
continuous support.
REFERENCES
1. Lin, W.; He, Z.; Zhang, H.; Zhang, X.; Mi, A.; Jiang, Y. Amino
Acid Anhydride Hydrochlorides as Acylating Agents in Friedel-Crafts
Reaction: A Practical Synthesis of l-Homophenylalanine. Synthesis
2001, 2001, 1007.
2. Berkeš, D.; Kolarovič, A.; Považanec, F. Stereoselective sodium
borohydride reduction, catalyzed by manganese(II) chloride, of γ-oxo-
α-amino acids. A practical approach to syn-γ-hydroxy-α-amino acids.
Tetrahedron Lett. 2000, 41, 5257.
3. (a) Ďuriš, A.; Wiesenganger, T.; Moravčíková, D.; Baran, P.;
Kožíšek, J.; Daïch, A.; Berkeš, D. Expedient and Practical Synthesis
of CERT-Dependent Ceramide Trafficking Inhibitor HPA-12 and Its
Analogues. Org. Lett. 2011, 13, 1642; (b) Ďuriš, A.; Berkeš, D.;
Jakubec, P. Stereodivergent synthesis of cyclic γ-aminobutyric acid –
GABA analogues. Tetrahedron Lett. 2019, 60, 480.
4. (a) Dardir, A. H.; Hazari, N.; Miller, S. J.; Shugrue, C. R.
Palladium-Catalyzed Suzuki–Miyaura Reactions of Aspartic Acid
Derived Phenyl Esters. Org. Lett. 2019, 21, 5762; (b) Golubev, A. S.;
Sewald, N.; Burger, K. Synthesis of γ-oxo α-amino acids from L-
aspartic acid. Tetrahedron 1996, 52, 14757.
5. (a) Yang, C.-F.; Shen, C.; Wang, J.-Y.; Tian, S.-K. A Highly
Diastereoselective Decarboxylative Mannich Reaction of β-Keto Acids
with Optically Active N-Sulfinyl α-Imino Esters. Org. Lett. 2012, 14,
3092; (b) Zhang, Y.; Li, J.-K.; Zhang, F.-G.; Ma, J.-A. Catalytic
Asymmetric Access to Noncanonical Chiral α-Amino Acids from
Cyclic Iminoglyoxylates and Enamides. J. Org. Chem. 2020, 85, 5580;
(c) Perera, S.; Sinha, D.; Rana, N. K.; Trieu-Do, V.; Zhao, J. C.-G.
List–Barbas–Mannich Reaction Catalyzed by Modularly Designed
Organocatalysts. J. Org. Chem. 2013, 78, 10947.
6. Jousseaume, T.; Wurz, N. E.; Glorius, F. Highly Enantioselective
Synthesis of α-Amino Acid Derivatives by an NHC-Catalyzed
Intermolecular Stetter Reaction. Angew. Chem. Int. Ed. 2011, 50, 1410.
7. (a) Yan, M.; Lo, J. C.; Edwards, J. T.; Baran, P. S. Radicals:
Reactive Intermediates with Translational Potential. J. Am. Chem. Soc.
2016, 138, 12692; (b) Zard, S. Z. Radicals in Action: A Festival of
Radical Transformations. Org. Lett. 2017, 19, 1257.
8. (a) Easton, C. J. Free-Radical Reactions in the Synthesis of α-
Amino Acids and Derivatives. Chem. Rev. 1997, 97, 53; (b) Hansen, S.
G.; Skrydstrup, T., Modification of Amino Acids, Peptides, and
Carbohydrates through RadicalChemistry. In Radicals in Synthesis II,
Gansäuer, A., Ed. Springer Berlin Heidelberg: Berlin, Heidelberg,
2006; pp 135; (c) Deska, J., Radical-Mediated Synthesis of α-Amino
Acids and Peptides. In Amino Acids, Peptides and Proteins in Organic
Chemistry, 2011; pp 115; (d) Brandhofer, T.; García Mancheño, O.
Site-Selective C-H Bond Activation/Functionalization of Alpha-
Amino Acids and Peptide-Like Derivatives. Eur. J. Org. Chem. 2018,
2018, 6050; (e) Liu, J.-Q.; Shatskiy, A.; Matsuura, B. S.; Kärkäs, M.
D. Recent Advances in Photoredox Catalysis Enabled
Functionalization of α-Amino Acids and Peptides: Concepts, Strategies
and Mechanisms. Synthesis 2019, 51, 2759; (f) Bottecchia, C.; Noël, T.
Photocatalytic Modification of Amino Acids, Peptides, and Proteins.
Chem. Eur. J. 2019, 25, 26; (g) Larionov, V. A.; Stoletova, N. V.;
Maleev, V. I. Advances in Asymmetric Amino Acid Synthesis Enabled
by Radical Chemistry. Adv. Syn. Catal. 2020, 362, 4325; (h) Aguilar
Troyano, F. J.; Merkens, K.; Anwar, K.; Gomez-Suarez, A. Radical-
Based Synthesis and Modification of Amino Acids. Angew. Chem. Int.
Ed. 2020, DOI: 10.1002/anie.202010157.
9. (a) Beckwith, A. L. J.; Chai, C. L. L. Diastereoselective radical
addition to derivatives of dehydroalanine and of dehydrolactic acid.
Chem. Commun. 1990, 1087; (b) Axon, J. R.; Beckwith, A. L. J.
Diastereoselective radical addition to methyleneoxazolidinones: an
enantioselective route to α-amino acids. Chem. Commun. 1995, 549.
10. Merkens, K.; Aguilar Troyano, F. J.; Djossou, J.; Gómez-
Suárez, A. Synthesis of Unnatural α-Amino Acid Derivatives via Light-
Mediated Radical Decarboxylative Processes. Adv. Syn. Catal. 2020,
362, 2354.
11. (a) Zheng, L.; Xia, P.-J.; Zhao, Q.-L.; Qian, Y.-E.; Jiang, W.-
N.; Xiang, H.-Y.; Yang, H. Photocatalytic Hydroacylation of Alkenes
by Directly Using Acyl Oximes. J. Org. Chem. 2020; (b) Zhang, M.;
Yuan, X. A.; Zhu, C.; Xie, J. Deoxygenative Deuteration of Carboxylic
Acids with D2O. Angew. Chem. Int. Ed. 2019, 58, 312; (c) Martinez
Alvarado, J. I.; Ertel, A. B.; Stegner, A.; Stache, E. E.; Doyle, A. G.
Direct Use of Carboxylic Acids in the Photocatalytic Hydroacylation
of Styrenes To Generate Dialkyl Ketones. Org. Lett. 2019; (d) Zhang,
M.; Xie, J.; Zhu, C. A general deoxygenation approach for synthesis
of ketones from aromatic carboxylic acids and alkenes. Nat. Commun.
2018, 9, 3517; (e) Stache, E. E.; Ertel, A. B.; Rovis, T.; Doyle, A. G.
Generation of Phosphoranyl Radicals via Photoredox Catalysis Enables
Voltage–Independent Activation of Strong C–O Bonds. ACS Catal.
2018, 11134.
12. Rossi-Ashton, J. A.; Clarke, A. K.; Unsworth, W. P.; Taylor,
R. J. K. Phosphoranyl Radical Fragmentation Reactions Driven by
Photoredox Catalysis. ACS Catal. 2020, 7250.
13. See Supporting Information for further details.
14. Shang, T.-Y.; Lu, L.-H.; Cao, Z.; Liu, Y.; He, W.-M.; Yu, B.
Recent advances of 1,2,3,5-tetrakis(carbazol-9-yl)-4,6-
dicyanobenzene (4CzIPN) in photocatalytic transformations. Chem.
Commun. 2019, 55, 5408.
15. Potential side reactions arising from interactions of the excited
photocatlayst with cinnamic acid, might be the cause of the observed
complex mixture.
16. Lowry, M. S.; Goldsmith, J. I.; Slinker, J. D.; Rohl, R.; Pascal,
R. A.; Malliaras, G. G.; Bernhard, S. Single-Layer Electroluminescent
Devices and Photoinduced Hydrogen Production from an Ionic
Iridium(III) Complex. Chem. Mat. 2005, 17, 5712.
17. Pandey, G.; Pooranchand, D.; Bhalerao, U. T. Photoinduced
single electron transfer activation of organophosphines: Nucleophilic
trapping of phosphine radical cation. Tetrahedron 1991, 47, 1745.
5
Insert Table of Contents artwork here
N
O
O
Cbz
t
Bu
OH
O
+
N
O
O
O
Cbz
t
Bu
PC
PR
3
O
O
P
O
– OPR
3
Abundant starting materials+ No chiral catalyst+ (hetero)aromatic & vinylic
carboxylic acids
+
