Stereospecific Protodeauration/Transmetalation Generating Configurationally Stable P-Metalated Nucleoside Derivatives

Article abstract of DOI:10.1002/ejoc.201800397

Highly efficient transmetalation between gold phosphites and iodopalladium species is presented. In addition to successful transfer of cyclic and acyclic phosphites, studies involving P-chiral substrates revealed that an initial protodeauration as well as the target transmetalation were both stereospecific, and that the overall process occurred with retention of configuration at phosphorus. Building on the mechanistic work, a catalytic approach to the synthesis of chiral P-arylated nucleoside derivatives was developed. This chemistry has the potential to be easily adapted for the preparation of a diverse group of P-chiral species.

Full text of DOI:10.1002/ejoc.201800397

A Journal of
Accepted Article
Title: Stereospecific Protodeauration/Transmetalation Generating
Configurationally Stable P-Metalated Nucleoside Derivatives
Authors: Robert A. Stockland, Marcia E Richard, Rosa M Ciccarelli,
Kevin G Garcia, Erica J Miller, Stephanie L Casino, and
Robert D Pike
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To be cited as: Eur. J. Org. Chem. 10.1002/ejoc.201800397
Link to VoR: http://dx.doi.org/10.1002/ejoc.201800397
Supported by

10.1002/ejoc.201800397
European Journal of Organic Chemistry
COMMUNICATION
Stereospecific Protodeauration/Transmetalation Generating
Configurationally Stable P-Metalated Nucleoside Derivatives
Marcia E. Richard, Rosa M. Ciccarelli, Kevin J. Garcia, Erica J. Miller, Stephanie L. Casino, Robert. D.
Pike, and Robert A. Stockland Jr*
Abstract: Highly efficient transmetalation between gold phosphites
and iodopalladium species is presented. In addition to successful
transfer of cyclic and acyclic phosphites, studies involving P-chiral
substrates revealed that an initial protodeauration as well as the target
transmetalation were both stereospecific, and that the overall process
occurred with retention of configuration at phosphorus. Building on
the mechanistic work, a catalytic approach to the synthesis of chiral
P-arylated nucleoside derivatives was developed. This chemistry has
the potential to be easily adapted for the preparation of a diverse
group of P-chiral species.
For P-metallated examples, the [P(O)(OR)2]- group can be
described as either an P(III) O-anionic phosphito or aP(V)
phosphonato ligand (Figure 1).[19] These rigid explanations define
the ends of the continuum, and many M[P(O)(OR)2] species are
likely to reside between these extremes. Spectroscopic evidence
(31P NMR, vide infra) as well as a recent computational study
suggest that the metal-phosphorus bonding is often more
consistent with the former (L-type ligand).[20]
Bonding descriptions:
O
O
[M] P(OR)2
[M] P(OR)2
The transfer of organic fragments between metal centers
along with the concomitant exchange of a ligand such as a
halogen (transmetalation) remains a key step in many catalytic
transformations as well as the construction of discrete
organometallic species. Main group organometallics such as
organoboron reagents[1] along with tin and zinc compounds[2]
have been among the most common transmetalating agents used
in these reactions. Recently, organogold complexes have
received significant attention,[3, 4] and a number of mechanistic
and catalytic investigations have been reported demonstrating
that gold is an effective transmetalating agent for a number of
1-P(V)
phosphonato
1-P(III)
O-anionic phosphito
Typical reactivity:
X
[M']
O
O
[M']
X
(1)
(2)
[M] P(OR)2
[M] P(OR)2
This work:
O
O
[M']
-[M]
X
X
[M'] P(OR)2
[M] P(OR)2
other metals including Pd,[4] Fe,[5] Ru,[5] Sn,[6] Rh,[7] Ni, and
Figure 1. Descriptions for [M](P(O)(OR)2) species and their reactivity.
others.[8,
A subtle balance of electronic and steric factors
9]
controls the direction of transmetalation, and the reverse reaction
12]
has been observed[10] with boron[11,
and transition metals
In terms of their reactivity, coordination of the oxygen from the
P-O- fragment to a second metal center dominates the reactivity
between organophosphonate and [M](P(O)(OR)2) species with
additional metal complexes (eqn 1, Scheme 1).[21-26] Kläui-type
metalloligands remain some of the most well studied examples of
this class and provide an all oxygen donor environment for a host
of metal centers.[27-30] While the metal-phosphorus bond in Kläui
ligands and other [M](P(O)(OR)2) species is typically robust,
cleavage of these bonds in suitably functionalized substrates can
be remarkably facile.[31-33] Interest in this alternate reactivity has
been driven by a need to understand and predict the reactivity of
key intermediates in metal catalyzed P-C bond forming
reactions.[34-37]
including Pd,[13] Cu,[14, 15] Rh,[16] Sn,[17] and Zr.[18]
The mechanistic and catalytic studies involving gold-based
transmetalating agents have focused on carbon bound fragments
and little attention has been given to the transfer of functional
groups that were attached to the gold through a heteroatom such
as phosphorus. For [M](P(O)(OR)2) species, there are additional
complications that must be taken into account when predicting
reactivity patterns.
Descriptions of the bonding, solution
speciation, as well as their reactivity with other metals can be
quite complex.[19] Even simple classification of the [P(O)(OR)2]-
group as a X or L type ligand[20a] can be challenging (Figure 1).
The ability to transfer the [P(O)(OR)2]- group from one metal
to another is the subject of this work. Upon successful transfer,
the [P(O)(OR)2]- fragment can attach to the new metal through
phosphorus or as a 1-O-phosphite. To expose the reaction
pathways between gold and palladium, the reactivity of discrete
gold complexes bearing [P(O)(OR)2]- groups with representative
iodopalladium precursors has been studied.
[a]
[b]
M. E. Richard, R. M. Ciccarelli, K. J. Garcia, E. J. Miller, S. L.
Casino, Prof. R. A. Stockland Jr*
Department of Chemistry
Bucknell University
Lewisburg, Pennsylvania, USA 17837
E-mail: rstockla@bucknell.edu
http://www.facstaff.bucknell.edu/rstockla/
Prof. R. D. Pike,
Department of Chemistry
The College of William and Mary
Williamsburg, VA, USA, 23185
The initial studies utilized the iodopalladium complex (1) and
(JohnPhos)Au(P(O)(OEt)2) (2) as representative substrates
(Scheme 1).[32, 38] Although 2 could be accessed from alkyl[39] or
Supporting information for this article is given via a link at the end of
the document.
This article is protected by copyright. All rights reserved.

10.1002/ejoc.201800397
European Journal of Organic Chemistry
COMMUNICATION
alkynylgold[38] precursors, we found that arylgold species were
superior. The bulky dialkylbiaryl phosphine ligand (L1) was used
as the supporting ligand on the gold center to inhibit dynamic
processes[40] and generate a single species in solution.[38] In terms
of the bonding description for 2, the 31P chemical shift for the
[P(O)(OEt)2]- group in 2 ( = 111.4)[38] is shifted over 100 ppm
downfield from HP(O)(OEt)2, and is in the range of simple
phosphite gold complexes such as ((MeO)3P)AuCl[41] (= 121.0)
and ((PhO)3P)AuCl[42] ( = 109.7) . Indeed the chemical shift of 2
is further downfield than ((MeO)2(OH)P)AuCl[40] ( = 109.7). This
phosphinous acid complex was generated through displacement
of dimethylsulfide from Me2SAuCl by the phosphite tautomer of
HP(O)(OMe)2. This suggests that the bonding of the [P(O)(OEt)2]-
4 reacted with 1 faster than 3 or 5. Furthermore, the reaction was
not reversible under these conditions (see supporting information).
To assess the stereochemical outcome of the process, (RP)(-)
menthyl phenylphosphinate (8) was generated and screened
(Scheme 2).[43-45]
The protodeauration between 8 and
t
JohnPhosAu(C6H4 Bu) was stereospecific and cleanly generated
the gold phosphinate intermediate as a configurationally stable
single diastereomer (9) (31P  = 114.3, 67.0, JPP = 396.8 Hz).
Similar to 2, the 31P chemical shift of the [P(O)R2]- fragment in 9 is
indicative of an O-anionic phosphito ligand. The transmetalation
between (bipy)Pd(2,6-C6H3Me2)I and 9 was also stereospecific
and generated the palladium complex 10 as a single diastereomer
(31P  = 79.0). The transformation of 8 into 10 could be carried
out in steps or as a one-pot process (Scheme 2). X-ray quality
crystals of 10 were grown and analysis of the structure revealed
group
2 is consistent with the O-anionic P(III) phosphito
description (Figure 1).
an SP configuration at phosphorus.[46]
Thus, the overall
t
protodeauration/transmetalation process was stereospecific and
proceeded with a net retention of configuration at phosphorus.
LAu(C6H4 Bu)
[a]
HP(O)(OR)2
LAuP(O)(OR)2
O
O
P(OR)2
Me
I
P(OR)2
Me
(JohnPhos)Au(C6H4tBu)
C6H6, 115 °C, 16 h
O
P
O
P
2 5
( - )
Me
H
[Pd]
Me
[Pd]
Me
[Pd]
Me
Au
P
tBu
[b] (THF, 60 °C)
- LAuI
O
O
tBu
Ph
9
(dr = 90:1)
8
(RP)
1
6,7
)
(
(dr = 90:1)
bipyPd(I)(2,6-C6H3Me2)
C6H6, 65 °C, 16 h
O
O
O
LAu
P
LAu P(OEt)2
Me
Me
Me
Me
O
1
1
4
2
: L , 78%
5: L2, 71%
: L , 91%
Me
Me
3: L2, 94%
O
[Pd]
P
Me
O
P(OEt)2
Me
O
Me
Me
O
O
P
[Pd]
Me
10 (Sp)
70% (dr = 90:1)
[Pd] = (bipyPd)
Me
O
Me
[Pd]
[Pd] = (tBu2bipy)Pd
L1= JohnPhos
L2 = tBuXPhos
Me
6
2
: 92% from
7:
4
95% from
Scheme 2. Stereospecific protodeauration/transmetalation using a P-Chiral
menthyl phosphinate. Reaction conditions for step 1: LAuC6H4 Bu (0.13 M sol.
in C6H6) and 8 (1 equiv), 115 °C, 16 h. Step 2: (bipy)Pd(2,6-C6H3Me2)I (1 equiv)
was added (65 °C, 16 h). Yields are based upon isolated material, and the
diastereomeric ratios were determined using 1H NMR spectroscopy. Molecular
structure of 10 (SP) with thermal ellipsoids at 50% and hydrogens omitted.
Protodeauration/transmetalation.[c]
Reaction
conditions:
t
Scheme
1.
[a]LAuC6H4 Bu (0.22-0.27 M sol. in THF) and HP(O)(OR)2 (1 equiv for R = Et, 1.5
equiv for R = Pin), 60 °C, 16 h. [b] 2-5 (0.13-0.16 M sol. in THF) and 1 (1 equiv),
THF, 60 °C, 12-16 h. [c] isolated yields.
t
Stirring a solution of 1 with 2 (THF, 60 °C) cleanly generated
P-palladated 6 in high yield along with (JohnPhos)AuI. Monitoring
this reaction by 31P NMR spectroscopy showed gradual loss of
the signals for 1 and 2 along with growth of the signals for 6 (31P
 = 71.2) and (JohnPhos)AuI (31P  = 65.3). No oxygen
coordination or bridged species were detected by NMR
spectroscopy. The 31P chemical shift of the [P(O)(OEt)2]-
fragment in 6 is ~40 ppm upfield relative to 2, suggesting the
possibility of increased contribution from the 1-P(V) phosphonato
form. Thus, the bonding in 6 could lie between the two extremes
listed in Scheme 1. Thankfully, transmetalation between 1 and 2
was fast relative to reductive elimination from 6, and no traces of
reductive elimination products were detected. Building on this
observation, the chemistry was successfully extended to cyclic
secondary phosphites. The transmetalation was sensitive to the
steric bulk of the phosphine ligand on the gold phosphite as 2 and
Due to their importance in medicine and chemical biology,
significant effort has been devoted to designing and synthesizing
new functionalized nucleosides.[47]
While metalation of
nucleoside purine and pyrimidine bases is common, metalation at
phosphorus is remarkably rare.[48] To this end, we surmised that
a nucleoside derived secondary phosphite (11) would be a
convenient entry point for the metalation chemistry. Indeed,
t
protodeauration of JohnPhosAu(C6H4 Bu) by 11 (dr = 52:48)
generated the P-metallated gold complex (12, dr = 51:49,
Scheme 3). As a consequence of the methodology used for the
synthesis of 11,[49] a mixture of diastereomers was generated due
to the presence of the unresolved phosphorus center. Separation
of the diastereomers of 11 prior to the protodeauration step was
challenging; however, the metalated species (12) were
separable[50] and found to be configurationally stable in solution.
Transmetalation between 12 (dr = 51:49) and bipyPd(2,6-C6H3
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10.1002/ejoc.201800397
European Journal of Organic Chemistry
COMMUNICATION
Ph
N
Ph
Me2)I successfully generated the palladium nucleoside (13) (dr =
50:50) as well as JohnPhosAuI. This process was also
stereospecific as single diastereomers of 13 (13a and 13b) were
generated using 12a and 12b.
HN
N
O
O
HN
N
O
N
C6H5I
DMTO
O
DMTO
O
O
Ph
Ph
Pd2dba3 (2.5% Pd)
O
O
O
O
DPEPhos (2.5 %)
THF, 70 °C, 18 h
- L1AuI
HN
N
O
O
HN
N
O
O
O
O
N
N
P
P
DMTO
O
DMTO
CN
CN
base-free
Au
L1
O
O
O
O
L1Au(C6H4tBu)
C6H6, 60 °C, 24 h
O
O
12
(dr = 51:49)
12a (dr = 50:1)
12b
14 92 % (dr = 52:48)
83 % (dr = 70:1, from
14b 74 % (dr = 1:62, from 12b)
O
P
P
14a
12a
)
CN
CN
(dr = 1:35)
H
Au
L1
12
93% (dr = 51:49)
11
(dr = 52:48)
12a 40% (dr = 50:1)
12b
32% (dr = 1:35)
Scheme 4. Base-free stereospecific P-arylation. Reaction conditions: 12 (0.08
M sol. in THF), iodobenzene (1.1 equiv), Pd2dba3 (2.5% Pd), and DPEPhos
(2.5%) were heated at 70 °C for 18 h. Yields are based upon isolated material,
and the diastereomeric ratios were determined using 1H NMR spectroscopy.
Ph
(bipy)Pd(I)(2,6-C H3Me2)
THF, 60 °C, 12 h
-L1AuI
6
HN
O
O
N
DMTO
N
O
In summary, the transmetalation between P-metalated
phosphites and iodopalladium precursors was found to be quite
facile. The gold and palladium species presented herein could
represent different regions of the [P(O)(OR)2]- bonding continuum.
Despite these differences, stereochemical studies using P-chiral
substrates revealed that the protodeauration and transmetalation
reactions were both stereospecific, and the overall process
occurred with retention of configuration at phosphorus. Building
upon this, the preparation of chiral P-arylated nucleosides was
devised. This method has the potential to be easily adapted to the
preparation of a diverse group of P-chiral species. A strength of
this approach is the tolerance of process to both acid and base
sensitive functional groups. Future work will focus on extending
the scope of the P-C bond forming reaction and investigating
further applications of P-metallated nucleosides.
O
O
Me
O
N
P
CN
13
Pd
N
90% (dr = 50:50)
13a 88% (dr = 50:1, from 12a)
13b 12b
Me
82% (dr = 1:41, from
)
Scheme 3.
Stereospecific protodeauration/transmetalation.
Reaction
t
conditions: Preparation of 12: LAuC6H4 Bu (0.27 M sol. in THF) and 11 (1 equiv)
were heated at 60 °C for 24 h. Preparation of 13: 12 (0.08 M sol. in THF) and
(bipy)Pd(2,6-C6H3Me2)I (1.1 equiv) were heated at 60 °C for 12 h. Yields are
based upon isolated material, and the diastereomeric ratios were determined
using 1H NMR spectroscopy.
Building on the mechanistic work, a base-free stereospecific
cross-coupling for the preparation of P-arylated nucleosides was
devised (Scheme 4). Historically, these base-assisted P-C bond
forming reactions have been challenging to extend to these
substrates due to the sensitivity of the cyanoethyl protecting group
to the amine or mineral bases typically used in coupling
reactions.[51] Furthermore, the acid generated in the cross-
coupling reaction cannot simply be ignored due to the acid
sensitivity of the trityl protecting group. A recent solution to this
problem entailed the use of an epoxide as an HX scavenger.[49, 52]
For the chemistry described herein, using 12 as the [P(O)(OR)2]-
source alleviates the need for additives since the Au/Pd
transmetalation generates the requisite palladium phosphite
intermediate directly. A ligand screening study was used to
identify an effective catalyst system (see SI).[31][53] It should be
noted that the gold was not sacrificial and could be readily
Acknowledgements
The authors acknowledge the National Science Foundation for
generous support of this work (Grant CHE-1300088) as well as
the funds to purchase the NMR spectrometer (Grant CHE-
0521108), and are indebted to NSF (CHE-0443345) and the
College of William and Mary for the purchase of the X-ray
equipment.
The authors thank Michael Krout for helpful
discussions.
Keywords: Gold • palladium • phosphonate • stereospecific •
protodeauration
[1] A. J. J. Lennox, G. C. Lloyd-Jones, Angew. Chem. Int. Ed. 2013, 52, 7362-
7370.
recovered as JohnPhosAuI.
The catalytic process was
stereospecific and generated single diastereomers of the P-
arylated nucleoside derivative when the metalated nucleosides
(12a and 12b) were used. This is a valuable method for the
stereospecific synthesis of P-C bonds due to its mild conditions
and tolerance of sensitive protecting groups.
[2] J. Choi, G. C. Fu, Science 2017, 356, 152-160.
[3] M. Joost, A. Amgoune, D. Bourissou, Angew. Chem. Int. Ed. 2015, 54,
15022-15045. M. Joost, A. Amgoune, D. Bourissou, Angew. Chem.
2015, 127, 15234-15258.
[4] J. J. Hirner, Y. Shi, S. A. Blum, Acc. Chem. Res. 2011, 44, 603-613.
[5] A. S. K. Hashmi, L. Molinari, Organometallics 2011, 30, 3457-3460.
This article is protected by copyright. All rights reserved.

10.1002/ejoc.201800397
European Journal of Organic Chemistry
COMMUNICATION
[6] Y. Chen, M. Chen, Y. Liu, Angew. Chem. Int. Ed. 2012, 51, 6181-6186. Y.
Chen, M. Chen, Y. Liu, Angew. Chem. 2012, 124, 6285-6290.
[7] Y. Shi, S. A. Blum, Organometallics 2011, 30, 1776-1779.
[8] W. M. Khairul, M. A. Fox, N. N. Zaitseva, M. Gaudio, D. S. Yufit, B. W. Skelton,
A. H. White, J. A. K. Howard, M. I. Bruce, P. J. Low, Dalton Trans. 2009,
610-620.
[44] For recent reports on the synthesis of 8 and related compounds see: a) W.-
M. Wang, L.-J. Liu, C.-Q. Zhao, L.-B. Han, Eur. J. Org. Chem. 2015, 2015,
2342-2345. b) R. Bigler, A. Mezzetti, Org. Process Res. Dev. 2016, 20,
253-261. c) O. Berger and J.-L. Montchamp Org. Biomol. Chem. 2016,
14, 7552-7562. d) D. Gatineau, L. Giordano, G. Buono J. Am. Chem. Soc.
2011, 133, 10728-10731. For recent reports on the use of 8 and related
compounds in stereospecific functionalizations see: e) Q. Xu, C.-Q. Zhao,
L.-B. Han, J. Am. Chem.Soc. 2008, 130, 12648-12655; f) L.-B. Han, C.-
Q. Zhao, J. Org. Chem. 2005, 70, 10121-10123; g) G. Wang, R. Shen,
Q. Xu, M. Goto, Y. Zhao, L.-B. Han, J. Org. Chem. 2010, 75, 3890-3892;
h) Y. Zhou, G. Wang, Y. Saga, R. Shen, M. Goto, Y. Zhao, L.-B. Han, J.
Org. Chem. 2010, 75, 7924-7927. i) O. I. Kolodiazhnyi, A. Kolodiazhna,
Tetrahedron: Asymmetry 2017, 28, 1651-1674. j) O. Berger and J.-L.
Montchamp, Angew. Chem. Int. Ed. 2013, 52, 11377-11380. k) O. Berger
and J.-L. Montchamp Angew. Chem. 2013, 125, 11587-11590. l) L.-J.
Liu, W.-M. Wang, L. Yao, F.-J. Meng, Y.-M. Sun, H. Xu, Z.-Y. Xu, Q. Li,
C.-Q. Zhao, L.-B. Han, J. Org. Chem. 2017, 82, 11990-12002.
[45] Han has studied the oxidative addition of 8 and related compounds to low
valent metal centers and found that the process occurs with retention of
stereochemistry. a) L. -B. Han, C. -Q. Zhao, S. -Y. Onozawa, M. Goto,
M. Tanaka, J. Am. Chem. Soc. 2002, 124, 3842-3843. b) J. Yang, T.
Chen, Y. Zhou, S.-F. Yin, L.-B. Han, Organometallics, 2015, 34, 5095-
5098.
[9] M. Contel, M. Stol, M. A. Casado, G. P. M. van Klink, D. D. Ellis, A. L. Spek,
G. van Koten, Organometallics 2002, 21, 4556-4559.
[10] K. Osakada, T. Yamamoto, Coord. Chem. Rev. 2000, 198, 379-399.
[11] J. J. Hirner, S. A. Blum, Tetrahedron 2015, 71, 4445-4449.
[12] E. Chong, S. A. Blum, J. Am. Chem. Soc. 2015, 137, 10144-10147.
[13] A. Toledo, I. Meana, A. C. Albéniz, Chem. -Eur. J. 2015, 21, 13216-13220.
[14] K. Osakada, R. Sakata, T. Yamamoto, J. Chem. Soc. Dalton Trans. 1997,
1265-1266.
[15] K. Osakada, M. Hamada, T. Yamamoto, Organometallics 2000, 19, 458-
468.
[16] C. Werlé, R. Goddard, A. Fürstner, Angew. Chem. Int. Ed. 2015, 54, 15452-
15456. C. Werlé, R. Goddard, A. Fürstner, Angew. Chem. 2015, 127,
15672-15676.
[17] E. S. Borren, A. F. Hill, R. Shang, M. Sharma, A. C. Willis, J. Am. Chem.
Soc. 2013, 135, 4942-4945.
[18] T. P. Cornell, Y. Shi, S. A. Blum, Organometallics 2012, 31, 5990-5993.
[19] P. Sutra, A. Igau, Coord. Chem. Rev. 2016, 308, 97-116.
[20] a. M. L. H. Green, J. Organomet. Chem. 1995, 500, 127-148. E. Lebon, R.
Sylvain, R. E. Piau, C. Lanthony, J. Pilme, P. Sutra, M. Boggio-Pasqua,
J.-L. Heully, F. Alary, A. Juris, A. Igau, Inorg. Chem. 2014, 53, 1946-1948.
[21] K. J. Gagnon, H. P. Perry, A. Clearfield, Chem. Rev. 2012, 112, 1034-1054.
[22] G. K. H. Shimizu, R. Vaidhyanathan, J. M. Taylor, Chem. Soc. Rev. 2009,
38, 1430-1449.
[46] CCDC 1823878 contains the supplementary crystallographic data for this
paper. These data can be obtained free of charge from The Cambridge
Crystallographic Data Centre.
[47] a) The compounds presented herein are labelled as nucleosides instead
of nucleotides since they do not contain a formal phosphate group. b).
D. A. DiRocco, Y. Ji, E. C. Sherer, A. Klapars, M. Reibarkh, J. Dropinski,
R. Mathew, P. Maligres, A. M. Hyde, J. Limanto, A. Brunskill, R. T. Ruck,
L.-C. Campeau, I. W. Davies, Science, 2017, 356, 426-430.
[23] S.-S. Bao, L.-M. Zheng, Coord. Chem. Rev. 2016, 319, 63-85.
[24] T. Schrader, J. Inclusion Phenom. Macrocyclic Chem. 1999, 34, 117-129.
[25] T.-Y. Ma, Z.-Y. Yuan, Chemsuschem. 2011, 4, 1407-1419.
[26] I. Kuzu, I. Krummenacher, J. Meyer, F. Armbruster, F. Breher, Dalton Trans.,
2008, 5836.
[48] a) R. T. Dalla, D. E. Bergstrom, J. Org. Chem. 1994, 59, 2418-2422. b) O.
Pav, M. H. Caruthers, Tetrahedron Lett. 2009, 50, 5015-5017.
[49] S. Abbas, R. D. Bertram, C. J. Hayes, Org. Lett. 2001, 3, 3365-3367.
[50] We recently reported the separation of phosphoramidite diastereomers
using a similar metalation approach. E. J. Miller, K. J. Garcia, E. C.
Holahan, R. M. Ciccarelli, R. A. Bergin, S. L. Casino, T. L. Bogaczyk, M.
R. Krout, P. M. Findeis, R. A. Stockland Jr., Inorg. Chem. 2014, 53,
12680-12682.
[27] W. -H. Leung, Q.-F. Zhang, X.-Y. Yi, Coord. Chem. Rev. 2007, 251, 2266-
2279.
[28] W. Kläui, H. Neukomm, H. Werner, G. Huttner, Chem. Ber. 1977, 110,
2283-2289.
[29] W. Kläui, Angew. Chem. Int. Ed. 1990, 29, 627-637. W. Kläui, Angew.
Chem. 1990, 102, 661-670.
[51] For P-arylation reactions involving nucleoside derivatives lacking the
cyanoethyl protecting group see: a) M. Kalek, A. Ziadi, J. Stawinski Org.
Lett. 2008, 10, 4637-4640. b) M. Kalek, M. Jezowska, J. Stawinski Adv.
Synth. Cat. 2009, 351, 3207-3216.
[30] V. M. Krishnan, H. D. Arman, Z. J. Tonzetich, Dalton Trans. 2017, 46, 1186-
1193.
[31] M. C. Kohler, T. V. Grimes, X. Wang, T. R. Cundari, R. A. Stockland Jr.,
Organometallics 2009, 28, 1193-1201.
[52] S. Abbas, C. J. Hayes, Tetrahedron Lett. 2000, 41, 4513-4517.
[53] T. Hirao, T. Masunaga, Y. Ohshiro, T. Agawa, Synthesis 1981, 56-57.
[32] M. C. Kohler, R. A. Stockland Jr., N. P. Rath, Organometallics 2006, 25,
5746-5756.
[33] M. Kalek, J. Stawinski, Organometallics 2007, 26, 5840-5847.
[34] F. M. J. Tappe, V. T. Trepohl, M. Oestreich, Synthesis 2010, 3037-3062.
[35] I. P. Beletskaya, M. A. Kazankova, Russ. J. Org. Chem. 2002, 38, 1391-
1430.
[36] C. Queffelec, M. Petit, P. Janvier, D. A. Knight, B. Bujoli, Chem. Rev. 2012,
112, 3777-3807.
[37] C. S. Demmer, N. Krogsgaard-Larsen, L. Bunch, Chem. Rev. 2011, 111,
7981-8006.
[38] G. F. Manbeck, M. C. Kohler, M. R. Porter, R. A. Stockland Jr., Dalton Trans.
2011, 40, 12595-12606.
[39] C. Hollatz, A. Schier, H. Schmidbaur, Chem. Ber. 1997, 130, 1333-1338.
[40] C. Hollatz, A. Schier, H. Schmidbaur, Inorg. Chim. Acta 2000, 300-302,
191-199.
[41] C. E. Strasser, S. Cronje, H. Schmidbaur, H. G. Raubenheimer, J.
Organomet. Chem. 2006, 691, 4788-4796.
[42] A. Leyva-Perez, J. R. Cabrero-Antonino, A. Cantin, A. Corma, J. Org. Chem.
2010, 75, 7769.
[43] a) T. L. Emmick, R. L. Letsinger, J. Am. Chem. Soc. 1968, 90, 3459–3465.
b) W. B. Farnham, R. K. Murray, K. Mislow, J. Am. Chem. Soc. 1970, 92,
5809–5810.
This article is protected by copyright. All rights reserved.

10.1002/ejoc.201800397
European Journal of Organic Chemistry
COMMUNICATION
Layout 2:
COMMUNICATION
Marcia E. Richard, Rosa M. Ciccarelli,
Kevin J. Garcia, Erica J. Miller,
Stephanie L. Casino, Robert. D. Pike,
and Robert A. Stockland Jr*
Page No. – Page No.
Stereospecific
A stereospecific protodeauration/transmetalation sequence facilitated the synthesis
of configurationally stable P-metalated species. Mechanistic studies using model
systems revealed the overall process to occur with retention of stereochemistry.
This methodology was adapted for the synthesis of chiral P-arylated nucleoside
derivatives.
Protodeauration/Transmetalation
Generating Configurationally Stable
P-metalated Nucleoside Derivatives.
This article is protected by copyright. All rights reserved.