Enantioselective Coupling of Dienes and Phosphine Oxides

Article abstract of DOI:10.1021/jacs.8b11150

We report a Pd-catalyzed intermolecular hydrophosphinylation of 1,3-dienes to afford chiral allylic phosphine oxides. Commodity dienes and air stable phosphine oxides couple to generate organophosphorus building blocks with high enantio- and regiocontrol. This method constitutes the first asymmetric hydrophosphinylation of dienes.

Full text of DOI:10.1021/jacs.8b11150

Communication
pubs.acs.org/JACS
Cite This: J. Am. Chem. Soc. XXXX, XXX, XXX−XXX
Enantioselective Coupling of Dienes and Phosphine Oxides
Shao-Zhen Nie,†,‡ Ryan T. Davison,† and Vy M. Dong*,†
†Department of Chemistry, University of California, Irvine, California 92697, United States
‡College of Pharmacy, Liaocheng University, Liaocheng, Shandong 252059, China
S
* Supporting Information
Table 1. Ligand and Acid Effects on Asymmetric
Hydrophosphinylation of 1a
a
ABSTRACT: We report a Pd-catalyzed intermolecular
hydrophosphinylation of 1,3-dienes to afford chiral allylic
phosphine oxides. Commodity dienes and air stable
phosphine oxides couple to generate organophosphorus
building blocks with high enantio- and regiocontrol. This
method constitutes the first asymmetric hydrophosphiny-
lation of dienes.
onjugated dienes are versatile motifs for constructing
Cmolecules that range from natural products to synthetic
polymers.1,2 In recent years, hydrofunctionalization has
emerged as an attractive and atom-economical3 method to
transform dienes into valuable building blocks.4 In comparison
to other hydrofunctionalizations (e.g., hydroboration or
hydroformylation), hydrophosphinylation remains in its
infancy (Figure 1). Hirao first coupled isoprene and diethyl
phosphonate to furnish an allylic phosphonate, albeit with low
efficiency (10% yield) and at an elevated temperature (150
°C).5 Tanaka later improved the hydrophosphorylation of 1,3-
dienes by using a more reactive pinacol-derived phosphonate
to synthesize allylphosphonates.6 While promising, this
strategy has been restricted to producing achiral regioisomers
or racemic mixtures.7 Given the potential for chiral phosphines
in catalysis,8 as well as the need for novel phosphine motifs in
medicine9 and agrochemical space,10 we sought to develop an
enantioselective hydrophosphinylation.11 Herein, we report the
transformation of several petroleum feedstocks and readily
a
Reaction conditions: 1a (0.12 mmol), 2a (0.10 mmol), Pd2(dba)3
(2.5 mol %), ligand (5.0 mol %), acid (20 mol %), toluene (0.40 mL),
3 h (unless otherwise noted). Yield determined by GC-FID analysis of
the reaction mixture, which was referenced to 1,3,5-trimethoxyben-
zene. Regioselectivity ratio (rr) is the ratio of 3aa to 4aa, which is
determined by 31P NMR analysis of reaction mixture. Enantiose-
lectivity ratio (er) determined by chiral SFC. See Supporting
Information (SI) for full structure of abbreviations used. Unless
b
otherwise noted, rr is >20:1. Standard conditions with (Ph)2P(O)-
c
d
OH as acid. Standard conditions with dppf as ligand. Isolated yield
of 3aa, 3.47 mmol scale, using Pd2(dba)3 (0.50 mol %) and L3 (1.0
mol %) with standard conditions, 18 h.
available dienes into chiral phosphine oxide building blocks,
with high regio- and enantiocontrol.
Given previously reported asymmetric hydroamination12
and hydrothiolation13 of 1,3-dienes, we chose to focus on a
phosphorus nucleophile that would possess intermediate
nucleophilicity compared to amines and thiols. As part of
our reaction design, we imagined using phosphine oxides (2)
as P-based nucleophiles because they are air stable,
commercially available, and readily reduced to the correspond-
Figure 1. Inspiration for asymmetric hydrophosphinylation of 1,3-
dienes.
Received: October 16, 2018
© XXXX American Chemical Society
A
DOI: 10.1021/jacs.8b11150
J. Am. Chem. Soc. XXXX, XXX, XXX−XXX

Journal of the American Chemical Society
Communication
a
Table 2. Hydrophosphinylation of Various 1,3-Dienes
Table 3. Hydrophosphinylation of 1a with Various
a
Phosphine Oxides
a
Reaction conditions: 1 (0.12 mmol), 2a (0.10 mmol), Pd2(dba)3
(2.5 mol %), ligand (5.0 mol %), (Ph)2P(O)OH (20 mol %), toluene
(0.40 mL), 6 h. Isolated yield of 3. Regioselectivity ratio (rr) is the
ratio of 3 to 4, which is determined by 31P NMR analysis of reaction
b
mixture. Enantioselectivity determined by chiral SFC. (S)-DTBM-
SegPhos (5.0 mol %) instead of L3, see SI for structure, 24 h.
a
Reaction conditions: 1a (0.12 mmol), 2 (0.10 mmol), Pd2(dba)3
(2.5 mol %), ligand (5.0 mol %), (Ph)2P(O)OH (20 mol %), toluene
(0.40 mL), 6 h. Isolated yield of 3. Regioselectivity ratio (rr) is the
ratio of 3 to 4, which is determined by 31P NMR analysis of reaction
mixture. Enantioselectivity determined by chiral SFC. See SI for full
ing phosphine.14 In addition, the pKa of 2 (ca. 25)15 is between
that of amines and thiols. Although the phosphine oxide
reagent and its corresponding product could inhibit catalysis,
hydrophosphinylation of alkenes16 and alkynes17 using
transition-metal catalysis and photocatalysis has been reported.
Encouraged by these examples, we set out to identify a catalyst
that would overcome the established 1,4-addition pathway to
furnish the desired chiral isomer.
b
structure of abbreviations used. Reaction time is 24 h.
We began our investigations with the coupling of 1-
phenylbutadiene (1a) and commercially available 2a (Table
1). We examined a range of achiral bisphosphine ligands, with
both Rh and Pd precatalysts. While Rh showed no reactivity,
Pd was promising for the hydrophosphinylation of 1a. As
highlighted in Table 1A, we observed that the ligand bite angle
affected the efficiency of the hydrophosphinylation.18 Combin-
ing Pd2(dba)3 and ferrocene-based dppf offered optimal results
(90%, >20:1 rr). Catalytic amounts of acid provided an
increase in the reaction rate; P(V)-based Brønsted acids
proved to be the most effective for hydrophosphinylation
(Table 1B). In the absence of an acid cocatalyst, we observe
16% of product 3aa after 3 h and an 87% yield after 24 h.
Based on these results, we focused on the Josiphos ligand
family with diphenylphosphinic acid as a cocatalyst.19 As seen
in Table 1C, with Pd(L3) we could lower the catalyst loading
to 0.50 mol % and synthesize 3aa on gram scale while retaining
high reactivity (1.05 g, 91%) and selectivity (>20:1 rr, 95:5 er).
The er in the presence of different acids shows little variation
and ranges from 95:5 to 96:4.
Figure 2. Diastereodivergent hydrophosphinylation of 1a.
With these conditions in hand, we investigated the
hydrophosphinylation of various 1,3-dienes with phosphine
oxide 2a (Table 2). We found that a variety of 1-aryl
substituted dienes could be transformed to chiral products
3ba−3ja with moderate to high reactivity (36−88%) and
selectivity (>20:1 rr, 88:12−96:4 er). Dienes containing aryl
chlorides (3ca, 3ha, 3ia) offer higher reactivity than aryl
bromides (3da), potentially due to the mitigation of side
pathways initiated by oxidative addition into the C−X bond.
The petroleum feedstocks butadiene (1m) and isoprene (1n)
can be coupled with 2a to furnish chiral building blocks 3ma
B
DOI: 10.1021/jacs.8b11150
J. Am. Chem. Soc. XXXX, XXX, XXX−XXX

Journal of the American Chemical Society
Communication
Figure 3. Proposed mechanism and initial investigations of the Pd-catalyzed hydrophosphinylation of 1,3-dienes.
and 3na, respectively. We observed product mixtures of 3ma
and 3na that equally, or moderately, favor 3,4-addition over
the established 1,4-addition previously reported for the
hydrophosphorylation of butadiene6 (1m) and isoprene5,6
(1n). To examine if the allylic phosphine oxide products (3ma
and 3na) could racemize by a sigmatropic rearrangement,20 we
resubjected 3ma to the standard reaction conditions. After 12
h, we observed no change in the enantiomeric excess. The 1,2-
disubstituted diene (1k) and 1-alkyl substituted diene (1l)
transform to products 3ka and 3la, respectively, in the
presence of (S)-DTBM-SegPhos. This result suggests that
the diene substitution pattern must be matched with the
appropriate ligand family, an observation in agreement with
our previous studies on Rh-catalyzed hydrothiolation of 1,3-
dienes.13
Next, we investigated the hydrophosphinylation of 1a with
structurally and electronically different phosphine oxides
(Table 3). We observed high reactivity (3ab−3am, 51−
88%), regioselectivity (>20:1 rr), and enantioselectivity
(74:26−98:2 er). This coupling tolerates aryl (3ab−3ai),
heterocyclic (3aj), and alkyl (3ak) phosphine oxides. Mono-
(2a−2g), di- (2h), and trisubstituted (2i) aryl groups on the
phosphine oxide partner can be coupled with 1a to afford
enantioenriched products (3aa−3ai). Fused ring motifs, which
are the basis of a large class of ligand scaffolds, can also be
incorporated in the phosphine oxide partner to generate
products 3al and 3am.
Catalyst-controlled C−P bond formation would enable
selective access to diastereomers. To test this idea, we
prepared enantiopure phosphine oxide 2n bearing a tert-butyl
and phenyl group, a popular motif in chiral ligand design
(Figure 2).21 Depending on the enantiomer of the ligand L3
used, the (R,R)-diastereomer 3an22 or (R,S)-diastereomer 3an′
can be obtained with high diastereocontrol (95:5 and 91:9 dr,
respectively). This result represents a diastereodivergent
strategy for making phosphine oxides.
Based on literature precedence and our own observations,
we propose the mechanism depicted in Figure 3A. The Pd(0)
precatalyst undergoes ligand substitution with the bisphos-
phine ligand to form a chiral monomeric species I, and
subsequent oxidative addition to diphenylphosphinic acid
(HX) forms Pd−H species II. A related oxidative addition
has been implicated as a key step in the hydrophosphinylation
of terminal alkynes.17e In the absence of acid additives, we
observe a significant induction period.23 We reason that the
addition of an acid cocatalyst (i.e., diphenylphosphinic acid)
shortens the induction period and favors the Pd−H catalyst
(e.g., II). At this point, two different modes of diene 1
coordination lead to the major product 3 (path a) and the
minor product 4 (path b). In path a, species III undergoes
hydropalladation to provide the key Pd-π-allyl intermediate IV.
Species IV then undergoes a ligand exchange with phosphine
oxide 2 to form species V. Subsequent reductive elimination of
V furnishes the allylic phosphine oxide 3 and regenerates the
Pd-catalyst I.
To probe the mechanism, we conducted the following
experiments (Figure 3B−D). First, down deuterium-labeled
phosphine oxide d-2a was subjected to the standard reaction
conditions. In this experiment, we see deuterium incorporation
at the C1 (10% D) and C4 (64% D) positions of d-3ea. If
hydropalladation was irreversible, we should observe about a
6:1 mixture of regioisomers. In contrast, we observe >20:1 rr
and thus conclude that hydropalladation is reversible. Second,
(Z)-1-phenylbutadiene (Z-1a) was subjected to the hydro-
phosphinylation. We observed only the (E)-product 3aa
(>95% E content) in similar yield (74%) and regioselectivity
(>20:1 rr) compared to the model substrate (Table 1, 3aa,
90% yield, >20:1 rr). This result suggests that isomerization
occurs faster than C−P bond formation. Furthermore, excess
diene Z-1a is recovered with ca. 25% Z content, which is
consistent with a reversible hydropalladation and reversible
diene coordination. By subjecting toluoyl phosphine oxide 2e
to product 3aa under otherwise standard conditions, we
confirm that the allylic phosphine oxide 3aa cannot undergo
further substitution to form 3ae. Our proposal is in line with a
study on alkyne hydrophosphinylation, where Pd−P bond
cleavage requires elevated temperatures, and reductive
elimination is the turnover-limiting step.17e We observe that
alkyl-substituted dienes (1l−1n) form products (3la−3na)
with lower regioselectivity compared to the aryl-substituted
dienes (3ba−3ka). Thus, reductive elimination to form the
conjugated product appears to be favorable.
The direct construction of chiral phosphines and phosphine
oxides has previously been achieved via additions to Michael
C
DOI: 10.1021/jacs.8b11150
J. Am. Chem. Soc. XXXX, XXX, XXX−XXX

Journal of the American Chemical Society
Communication
acceptors or transition-metal catalyzed substitutions.24,25
Herein, we report a complementary way to access chiral
phosphine oxides. This study features the first enantioselective
hydrophosphinylation of dienes. Phosphine oxides and 1,3-
dienes can be coupled to furnish chiral allylic products in high
yields, regioselectivities, and enantioselectivities. Mechanistic
studies suggest that the coupling proceeds through a reversible
hydropalladation of the 1,3-diene partner, followed by
irreversible reductive elimination to afford chiral phosphine
oxide building blocks.
̈
(4) For select hydrofunctionalizations of dienes, see: (a) Lober, O.;
Kawatsura, M.; Hartwig, J. F. Palladium-Catalyzed Hydroamination of
1,3-Dienes: A Colorimetric Assay and Enantioselective Additions. J.
Am. Chem. Soc. 2001, 123, 4366−4367. (b) Page, J. P.; RajanBabu, T.
V. Asymmetric Hydrovinylation of 1-Vinylcycloalkenes. Reagent
Control of Regio- and Stereoselectivity. J. Am. Chem. Soc. 2012,
134, 6556−6559. (c) Zbieg, J. R.; Yamaguchi, E.; McInturff, E. L.;
Krische, M. J. Enantioselective C−H Crotylation of Primary Alcohols
via Hydrohydroxyalkylation of Butadiene. Science 2012, 336, 324−
327. (d) Park, B. Y.; Montgomery, T. P.; Garza, V. J.; Krische, M. J.
Ruthenium Catalyzed Hydrohydroxyalkylation of Isoprene with
Heteroaromatic Secondary Alcohols: Isolation and Reversible
Formation of the Putative Metallacycle Intermediate. J. Am. Chem.
Soc. 2013, 135, 16320−16323. (e) Chen, Q.-A.; Kim, D. K.; Dong, V.
M. Regioselective Hydroacylation of 1,3-Dienes by Cobalt Catalysis. J.
Am. Chem. Soc. 2014, 136, 3772−3775. (f) Saini, V.; O’Dair, M.;
Sigman, M. S. Synthesis of Highly Functionalized Tri- and
Tetrasubstituted Alkenes via Pd-Catalyzed 1,2-Hydrovinylation of
Terminal 1,3-Dienes. J. Am. Chem. Soc. 2015, 137, 608−611.
(g) Marcum, J. S.; Roberts, C. C.; Manan, R. S.; Cervarich, T. N.;
Meek, S. J. Chiral Pincer Carbodicarbene Ligands for Enantioselective
Rhodium-Catalyzed Hydroarylation of Terminal and Internal 1,3-
Dienes with Indoles. J. Am. Chem. Soc. 2017, 139, 15580−15583.
(h) Yang, X.-H.; Lu, A.; Dong, V. M. Intermolecular Hydroamination
of 1,3-Dienes To Generate Homoallylic Amines. J. Am. Chem. Soc.
2017, 139, 14049−14052. (i) Gui, Y.-Y.; Hu, N.; Chen, X.-W.; Liao,
L.-L.; Ju, T.; Ye, J.-H.; Zhang, Z.; Li, J.; Yu, D.-G. Highly Regio- and
Enantioselective Copper-Catalyzed Reductive Hydroxymethylation of
Styrenes and 1,3-Dienes with CO2. J. Am. Chem. Soc. 2017, 139,
17011−17014. (j) Adamson, N. J.; Hull, E.; Malcolmson, S. J.
Enantioselective Intermolecular Addition of Aliphatic Amines to
Acyclic Dienes with a Pd−PHOX Catalyst. J. Am. Chem. Soc. 2017,
139, 7180−7183. (k) Adamson, N. J.; Wilbur, K. C. E.; Malcolmson,
S. J. Enantioselective Intermolecular Pd-Catalyzed Hydroalkylation of
Acyclic 1,3-Dienes with Activated Pronucleophiles. J. Am. Chem. Soc.
2018, 140, 2761−2764. (l) Schmidt, V. A.; Kennedy, C. R.; Bezdek,
M. J.; Chirik, P. J. Selective [1,4]-Hydrovinylation of 1,3-Dienes with
Unactivated Olefins Enabled by Iron Diimine Catalysts. J. Am. Chem.
Soc. 2018, 140, 3443−3453. For reviews, see: (m) Hydrofunction-
alization. Topics in Organometallic Chemistry; Ananikov, V. P., Tanaka,
M., Eds.; Springer: Berlin, 2014; Vol. 343. (n) McNeill, E.; Ritter, T.
1,4-Functionalization of 1,3-Dienes With Low-Valent Iron Catalysts.
ASSOCIATED CONTENT
* Supporting Information
The Supporting Information is available free of charge on the
ACS Publications website at DOI: 10.1021/jacs.8b11150.
■
S
Experimental procedures and spectral data for all new
compounds (PDF)
Crystallographic data for 3an (CIF)
AUTHOR INFORMATION
Corresponding Author
*dongv@uci.edu
■
ORCID
Vy M. Dong: 0000-0002-8099-1048
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
Funding provided by UC Irvine, the National Institutes of
Health (R35GM127071), and the National Science Founda-
tion (CHE-1465263). S.-Z.N. thanks Liaocheng University for
a scholarship. We thank Dr. Joseph Ziller and Austin Ryan for
X-ray crystallographic analysis and the Jarvo Lab for use of
their SFC.
REFERENCES
■
́
Acc. Chem. Res. 2015, 48, 2330−2343. (o) Bezzenine-Lafollee, S.; Gil,
(1) For selected reviews on 1,3-dienes as building blocks, see:
(a) Nicolaou, K. C.; Snyder, S. A.; Montagnon, T.; Vassilikogiannakis,
G. The Diels-Alder Reaction in Total Synthesis. Angew. Chem., Int. Ed.
2002, 41, 1668−1698. (b) Reymond, S.; Cossy, J. Copper-Catalyzed
Diels-Alder Reactions. Chem. Rev. 2008, 108, 5359−5406. (c) Chen,
J.-R.; Hu, X.-Q.; Lu, L.-Q.; Xiao, W.-J. Formal [4 + 1] Annulation
Reactions in the Synthesis of Carbocyclic and Heterocyclic Systems.
R.; Prim, D.; Hannedouche, J. First-Row Late Transition Metals for
Catalytic Alkene Hydrofunctionalisation: Recent Advances in C−N,
C−O, and C−P Bond Formation. Molecules 2017, 22, 1901−1929.
(5) Hirao, T.; Masunaga, T.; Yamada, N.; Ohshiro, Y.; Agawa, T.
Palladium-catalyzed New Carbon-Phosphorous Bond Formation. Bull.
Chem. Soc. Jpn. 1982, 55, 909−913.
(6) Mirzaei, F.; Han, L.-B.; Tanaka, M. Palladium-catalyzed
hydrophosphorylation of 1,3-dienes leading to allylphosphonates.
Tetrahedron Lett. 2001, 42, 297−299.
(7) Two additional examples have been reported for the coupling of
hydrophosphorous acid (H3PO2) and a 1,3-diene that yield allylic
phosphinic acids via Pd-catalyzed 1,4-addition; see: Bravo-Altamirano,
K.; Abrunhosa-Thomas, I.; Montchamp, J.-L. Palladium-Catalyzed
Reactions of Hypophosphorous Compounds with Allenes, Dienes,
and Allylic Electrophiles: Methodology for the Synthesis of Allylic H-
Phosphinates. J. Org. Chem. 2008, 73, 2292−2301.
(8) For select reviews of phosphines in catalysis, see: (a) Tolman, C.
A. Steric effects of phosphorus ligands in organometallic chemistry
and homogeneous catalysis. Chem. Rev. 1977, 77, 313−348. (b) van
Leeuwen, P. W. N. M.; Kamer, P. C. J.; Reek, J. N. H.; Dierkes, P.
Ligand Bite Angle Effects in Metal-catalyzed C−C Bond Formation.
Chem. Rev. 2000, 100, 2741−2770. (c) Noyori, R.; Ohkuma, T.
Asymmetric Catalysis by Architectural and Functional Molecular
Engineering: Practical Chemo- and Stereoselective Hydrogenation of
Ketones. Angew. Chem., Int. Ed. 2001, 40, 40−73. (d) Xiao, Y.; Guo,
H.; Kwon, O. Nucleophilic Chiral Phosphines: Powerful and Versatile
Chem. Rev. 2015, 115, 5301−5365. (d) Buschleb, M.; Dorich, S.;
̈
Hanessian, S.; Tao, D.; Schenthal, K. B.; Overman, L. E. Synthetic
Strategies toward Natural Products Containing Contiguous Stereo-
genic Quaternary Carbon Atoms. Angew. Chem., Int. Ed. 2016, 55,
4156−4186.
(2) For reviews on polymerization of 1,3-dienes, see: (a) Monakov,
Y. B.; Mullagaliev, I. R. Ionic and coordination diene polymerization
and organic derivatives of main group metals. Russ. Chem. Bull. 2004,
53, 1−9. (b) Friebe, L.; Nuyken, O.; Obrecht, W. Neodymium Based
Ziegler/Natta Catalysts and their Application in Diene Polymer-
ization. Adv. Polym. Sci. 2006, 204, 1−154. (c) Zhang, Z.; Cui, D.;
Wang, B.; Liu, B.; Yang, Y. Polymerization of 1,3-Conjugated Dienes
with Rare-Earth Metal Precursors. Struct. Bonding (Berlin, Ger.) 2010,
137, 49−108. (d) Valente, A.; Mortreux, A.; Visseaux, M.; Zinck, P.
Coordinative Chain Transfer Polymerization. Chem. Rev. 2013, 113,
3836−3857. (e) Takeuchi, D. Stereoselective Polymerization of
Conjugated Dienes. Encyclopedia of Polymer Science and Technology;
Wiley: New York, 2013; pp 1−25.
(3) Trost, B. M. The atom economya search for synthetic
efficiency. Science 1991, 254, 1471−1477.
D
DOI: 10.1021/jacs.8b11150
J. Am. Chem. Soc. XXXX, XXX, XXX−XXX

Journal of the American Chemical Society
Communication
Catalysts for Asymmetric Annulations. Aldrichimica Acta 2016, 49, 3−
13. (e) Ni, H.; Chan, W.-L.; Lu, Y. Phosphine-Catalyzed Asymmetric
Organic Reactions. Chem. Rev. 2018, 118, 9344−9411.
(18) For a review on ligand bite angle effects, see ref 8b.
(19) We also tried the PHOX ligand scaffold, which has
demonstrated high reactivity and enantioselectivity in Pd-catalyzed
diene hydroamination (see ref 4j) and hydroalkylation (see ref 4k),
but observed no reactivity.
(9) For reviews of phosphines in medicine, see: (a) Tiekink, E. R. T.
Phosphinegold(I) thiolatespharmacological use and potential.
Bioinorg. Chem. Appl. 2003, 1, 53−67. (b) Phillips, A. D.; Gonsalvi,
L.; Romerosa, A.; Vizza, F.; Peruzzini, M. Coordination chemistry of
1,3,5-triaza-7-phosphaadamantane (PTA): Transition metal com-
plexes and related catalytic, medicinal, and photoluminescent
applications. Coord. Chem. Rev. 2004, 248, 955−993. (c) Dominelli,
(20) Herriott, A. W.; Mislow, K. Rearrangement of allyl phosphinites
and optical stability of allyl phosphine oxides. Tetrahedron Lett. 1968,
9, 3013−3016.
(21) Luhr, S.; Holz, J.; Borner, A. The Synthesis of Chiral
̈
Phosphorus Ligands for use in Homogeneous Metal Catalysis.
ChemCatChem 2011, 3, 1708−1730.
B.; Correia, J. D. G.; Kuhn, F. E. Medicinal Applications of Gold(I/
̈
III)-Based Complexes Bearing N-Heterocyclic Carbene and Phos-
phine Ligands. J. Organomet. Chem. 2018, 866, 153−164.
(22) X-ray crystallography data confirmed the absolute configuration
of 3an, CCDC: 1868886. The absolute configuration of compounds
3aa−3am, 3an′, and 3ba−3na were assigned by analogy.
(23) See the Supporting Information for more details.
(10) For a select example of phosphines in agrochemicals, see:
(a) Schlipalius, D. I.; Valmas, N.; Tuck, A. G.; Jagadeesan, R.; Ma, L.;
Kaur, R.; Goldinger, A.; Anderson, C.; Kuang, J.; Zuryn, S.; Mau, Y.
S.; Cheng, Q.; Collins, P. J.; Nayak, M. K.; Schirra, H. J.; Hilliard, M.
A.; Ebert, P. R. A Core Metabolic Enzyme Mediates Resistance to
Phosphine Gas. Science 2012, 338, 807−810. For a review, see:
(b) Nath, N. S.; Bhattacharya, I.; Tuck, A. G.; Schlipalius, D. I.; Ebert,
P. R. Mechanisms of Phosphine Toxicity. J. Toxicol. 2011, 2011, 1−9.
(11) We are using the definition of hydrophosphinylation that refers
to the addition of a phosphine oxide to a degree of unsaturation; see:
Han, L.-B.; Choi, N.; Tanaka, M. Oxidative Addition of HP(O)Ph2 to
Platinum(0) and Palladium(0) Complexes and Palladium-Catalyzed
Regio- and Stereoselective Hydrophosphinylation of Alkynes. Organo-
metallics 1996, 15, 3259−3261.
(24) For select enantioselective additions to Michael acceptors, see:
(a) Carlone, A.; Bartoli, G.; Bosco, M.; Sambri, L.; Melchiorre, P.
Organocatalytic Asymmetric Hydrophosphination of α,β-Unsaturated
Aldehydes. Angew. Chem., Int. Ed. 2007, 46, 4504−4506. (b) Ibrahem,
́
I.; Rios, R.; Vesely, J.; Hammar, P.; Eriksson, L.; Himo, F.; Cordova,
A. Enantioselective Organocatalytic Hydrophosphination of α,β-
Unsaturated Aldehydes. Angew. Chem., Int. Ed. 2007, 46, 4507−
4510. (c) Feng, J.-J.; Chen, X.-F.; Shi, M.; Duan, W.-L. Palladium-
Catalyzed Asymmetric Addition of Diarylphosphines to Enones
toward the Synthesis of Chiral Phosphines. J. Am. Chem. Soc. 2010,
132, 5562−5563. (d) Chew, R. J.; Teo, K. Y.; Huang, Y.; Li, B.-B.; Li,
Y.; Pullarkat, S. A.; Leung, P.-H. Enantioselective phospha-Michael
addition of diarylphosphines to β,γ-unsaturated α-ketoesters and
amides. Chem. Commun. 2014, 50, 8768−8770. For a review, see:
(e) Pullarkat, S. A. Recent Progress in Palladium-Catalyzed
Asymmetric Hydrophosphination. Synthesis 2016, 48, 493−503.
(25) For select enantioselective transition-metal catalyzed sub-
stitutions, see: (a) Butti, P.; Rochat, R.; Sadow, A. D.; Togni, A.
Palladium-Catalyzed Enantioselective Allylic Phosphination. Angew.
Chem., Int. Ed. 2008, 47, 4878−4881. (b) Zhang, L.; Liu, W.; Zhao, X.
Carbon−Phosphorous Bond Formation by Enantioselective Palla-
dium-Catalyzed Allylation of Diphenylphosphine Oxide. Eur. J. Org.
Chem. 2014, 2014, 6846−6849. (c) Liu, C.; Wang, Q. Alkenylation of
C(sp3)−H Bonds by Zincation/Copper-Catalyzed Cross-Coupling
with Iodonium Salts. Angew. Chem., Int. Ed. 2018, 57, 4727−4731.
(12) Yang, X.-H.; Dong, V. M. Rhodium-Catalyzed Hydro-
functionalization: Enantioselective Coupling of Indolines and 1,3-
Dienes. J. Am. Chem. Soc. 2017, 139, 1774−1777.
(13) Yang, X.-H.; Davison, R. T.; Dong, V. M. Catalytic
Hydrothiolation: Regio- and Enantioselective Coupling of Thiols
and Dienes. J. Am. Chem. Soc. 2018, 140, 10443−10446.
(14) For reviews on reducing phosphine oxides to phosphines, see:
́
(a) Herault, D.; Nguyen, D. H.; Nuel, D.; Buono, G. Reduction of
secondary and tertiary phosphine oxides to phosphines. Chem. Soc.
́
Rev. 2015, 44, 2508−2528. (b) Kovacs, T.; Keglevich, G. The
Reduction of Tertiary Phosphine Oxides by Silanes. Curr. Org. Chem.
2017, 21, 569−585.
(15) Grayson, M.; Farley, C. E.; Streuli, C. A. Secondary phosphine
oxides: The effect of structure on acid strength and rates of cleavage
of disulfides. Tetrahedron 1967, 23, 1065−1078.
(16) For select hydrophosphinylations of alkenes, see: (a) Kawa-
guchi, S.-I.; Nomoto, A.; Sonoda, M.; Ogawa, A. Photoinduced
hydrophosphinylation of alkenes with diphenylphosphine oxide.
Tetrahedron Lett. 2009, 50, 624−626. (b) Yoo, W.-J.; Kobayashi, S.
Hydrophosphinylation of unactivated alkenes with secondary
phosphine oxides under visible-light photocatalysis. Green Chem.
2013, 15, 1844−1848. (c) Li, Z.; Fan, F.; Zhang, Z.; Xiao, Y.; Liu, D.;
Liu, Z.-Q. A silver-initiated free-radical intermolecular hydro-
phosphinylation of unactivated alkenes. RSC Adv. 2015, 5, 27853−
27856.
(17) For select hydrophosphinylations of alkynes, see: (a) Han, L.-
B.; Hua, R.; Tanaka, M. Phosphinic Acid Induced Reversal of
Regioselectivity in Pd-Catalyzed Hydrophosphinylation of Alkynes
with Ph2P(O)H. Angew. Chem., Int. Ed. 1998, 37, 94−96. (b) Han, L.-
B.; Zhao, C.-Q.; Tanaka, M. Rhodium-Catalyzed Regio- and
Stereoselective Addition of Diphenylphosphine Oxide to Alkynes. J.
Org. Chem. 2001, 66, 5929−5932. (c) Han, L.-B.; Zhang, C.; Yazawa,
H.; Shimada, S. Efficient and Selective Nickel-Catalyzed Addition of
H−P(O) and H−S Bonds to Alkynes. J. Am. Chem. Soc. 2004, 126,
5080−5081. (d) Rooy, S. V.; Cao, C.; Patrick, B. O.; Lam, A.; Love, J.
A. Alkyne hydrophosphinylation catalyzed by rhodium pyrazolylbo-
rate complexes. Inorg. Chim. Acta 2006, 359, 2918−2923. (e) Chen,
T.; Zhao, C.-Q.; Han, L.-B. Hydrophosphorylation of Alkynes
Catalyzed by Palladium: Generality and Mechanism. J. Am. Chem.
Soc. 2018, 140, 3139−3155. For a review, see: (f) Xu, Q.; Han, L.-B.
Metal-catalyzed additions of H−P(O) bonds to carbon−carbon
unsaturated bonds. J. Organomet. Chem. 2011, 696, 130−140.
E
DOI: 10.1021/jacs.8b11150
J. Am. Chem. Soc. XXXX, XXX, XXX−XXX