The Tetraethylphosphorodiamidate (OP(O)(NEt2)2) Directed Metalation Group (DMG). Directed ortho and Lateral Metalation and the Phospha Anionic Fries Rearrangement

Article abstract of DOI:10.1021/acs.orglett.0c00094

We report on the tetraethylphosphorodiamidate (-OP(O)(NEt₂)₂) group as an effective directed metalation group (DMG). Lithiation-electrophile quench of 1 provides a general synthesis of ortho-substituted aryl and naphthyl phosphorodiamidates 4-8. We also describe the phospha anionic ortho-Fries (AoF) rearrangement of the phosphorodiamidates 1a,1ba2 or 3 and its vinylogous counterpart to the ortho-tolyl phosphorodiamidates 5ba 13. Intermolecular competition experiments demonstrate the approximately equal DMG strength of the-OP(O)(NEt₂)₂ and the most powerful OCONEt₂ groups.

Full text of DOI:10.1021/acs.orglett.0c00094

pubs.acs.org/OrgLett
Letter
The Tetraethylphosphorodiamidate (OP(O)(NEt2)2) Directed
Metalation Group (DMG). Directed ortho and Lateral Metalation and
the Phospha Anionic Fries Rearrangement
Manlio Alessi, Jignesh J. Patel, Kristina Zumbansen, and Victor Snieckus*
Cite This: https://dx.doi.org/10.1021/acs.orglett.0c00094
Read Online
sı
*
Metrics & More
Article Recommendations
Supporting Information
ACCESS
ABSTRACT: We report on the tetraethylphosphorodiamidate
(−OP(O)(NEt2)2) group as an effective directed metalation group
(DMG). Lithiation-electrophile quench of 1 provides a general
synthesis of ortho-substituted aryl and naphthyl phosphorodiami-
dates 4−8. We also describe the phospha anionic ortho-Fries (AoF)
rearrangement of the phosphorodiamidates 1a,1b → 2 or 3 and its
vinylogous counterpart to the ortho-tolyl phosphorodiamidates
5b → 13. Intermolecular competition experiments demonstrate the
approximately equal DMG strength of the −OP(O)(NEt2)2 and
the most powerful OCONEt2 groups.
ur studies on the directed ortho metalation (DoM)
decarbamoylation of aryl O-carbamates earns this group a
latent DMG status.1e
O
reaction1 have established the O-carbamate (Figure 1A)
In the course of our search toward new oxygen-based
DMGs,4b we noted the relevant metalation/AoF studies that
had been performed by Melvin7 and Cambie8 on aryl
phosphates [Ar-OP(O)(OEt)2] (Figure 1C), by Modro9 on
the phenyl OP(O)(N(Me)Ph)2 system, by Dhawan and
Redmore10 on aryl 1,2- and 1,4-diphosphates, and by
Watanabe11 on the aryl phosphorodiamidate system (Figure
1D), in which the OP(O)(NMe2)2 DMG was shown to also be
a strong lateral metalation director. Lastly, Buono reported on
the anionic phospha-Fries rearrangement of chiral phosphor-
odiamidates as a route to chiral phosphoric diamides,12 and
Knochel revisited Watanabe’s DoM chemistry of the aryl
OP(O)(NMe2)2 system using the bimetallic base, (TMP)2Mg·
LiCl.13 These results speak to the current activity and the
future potential of this area of anionic aromatic chemistry.
Stimulated by the above studies, we investigated the aryl
tetraethylphosphorodiamidates (Ar-OP(O)(NEt2)2) system
(Figure 1, 1-Li) as a potentially suitable P-based DMG for
the development of more useful DoM, phospha AoF
rearrangement, and lateral metalation reactions than heretofore
established. Herein, we report the results of our work, and, in
the sequel,14 we describe cross coupling, remote anionic
phospha-Fries rearrangement reactions of aryl OP(O)(NEt2)2
Figure 1. Selected O-based directed metalation groups (DMGs).
as the strongest in the directed metalation group (DMG)
hierarchy,1a,2,3 and this class of substrates have gained
considerable value in methodology and target-oriented syn-
thesis.4 Their synthetic utility is fortified by the fact that aryl O-
carbamates undergo the anionic ortho Fries rearrangement
(AoF) to salicylamides4b,c,k and that, after DoM chemistry,
DMG conversion to the corresponding phenol derivatives may
be performed via mild Schwartz reagent reduction.5 The DoM
strategy received considerable impetus with the development
of Suzuki−Miyaura and Kumada−Corriu cross-coupling
methodologies for the OCONR2 and the OSO2NR2 (Figure
1B) DMGs, which consolidates a proactive DoM-cross
coupling nexus.6 At the same time, the Ni-catalyzed hydro-
Received: January 10, 2020
https://dx.doi.org/10.1021/acs.orglett.0c00094
© XXXX American Chemical Society
Org. Lett. XXXX, XXX, XXX−XXX
A

Organic Letters
pubs.acs.org/OrgLett
Letter
derivatives, and the synthesis of tricyclic oxaphosphorine
oxides, of potential interest as ligands in catalytic reactions.
Combined, these studies offer a contribution to the synthesis
of organophosphorus compounds15 and place the OP(O)-
(NEt2)2 group in the repertoire of O-based DMGs for renewed
evaluation in synthetic carbanionic chemistry of aromatic
molecules.
As expected from earlier work on naphthyl systems,21
a
similar outcome was observed for substrate 1d (Ar = 2-Naph)
for which preferential metalation and electrophile quench
occurred at the C3-position to afford compounds 7a, 7b, and
7c in good yields (see the Supporting Information). As a final
example, double metalation-iodine quench of a BINOL-
derived diphosphorodiamidate 1e (Ar = 1,1′-bi(2-Naph)) led
to the formation of 8 albeit in low yield, together with mono-
and di-iodinated products, thereby suffering in the isolation
and purification procedures (see the Supporting Information).
To probe the temperature for the onset of the phospha AoF
rearrangement, a solution of metalated 1a (R = H) was allowed
to warm to rt and led to the formation of 2a in 95% yield (see
Scheme 2). The synergistic metalation of 1c (R = 3-OMe),
In initiating our work, the known beneficial steric effects of
several CONR2 DMGs16−18 guided our choice of the bulkier
OP(O)(NEt2)2 DMG, which was expected to display a higher
stability at metalation temperatures above −105 °C used by
11
Watanabe on aryl OP(O)(NMe2)2 systems. Thus, the
phosphorodiamidate 1a (Ar = C6H5, Scheme 1), readily
Scheme 1. DoM and Electrophile Quench of Aryl
Tetraethylphosphorodiamidates 1a−1e
Scheme 2. DoM and Phospha AoF Rearrangement of Aryl
Tetraethylphosphorodiamidates 1a, 1c, 4d, and 1d
followed by phospha AoF rearrangement, gave 2b in very good
yield. A 2-fold excess base led to a very effective phospha AoF
on 4d (R = 2-Me), without intervention of potentially
competing lateral metalation (vide infra). However, the 2-
OP(O)(NEt2)2 naphthyl derivative 1d gave 3 in moderate
yield (56%) with recovery of starting material (40%). Thus, the
11
small enhancement of bulk from OP(O)(NMe2)2 to
a
b
OP(O)(NEt2)2 tunes the stability of this DMG to approx-
imately match that of OCONEt2 (Figure 1A), which undergoes
the AoF rearrangement at approximately −50 °C.4c
1.0 equiv TMEDA. 1.2 equiv LiTMP used.
prepared by the reaction of phenol with commercially available
tetraethylphosphorodiamidic chloride (ClPO(NEt2)2)19 in
quantitative yield, was subjected to the standard s-BuLi/
THF/−78 °C/1 h protocol, followed by treatment with
TMSCl. Gratifyingly, the 2-silylated phosphorodiamidate 4a
was obtained in 84% yield without any evidence of the
formation of the phospha AoF rearrangement product.
Generalization of the electrophile quench reaction followed
to yield derivatives 4b−4h in very good yields, with the
exception of the boronic acid quench product, which was
deemed to be unstable and therefore was isolated as the
pinacolate 4g. Good yields of products 5a and 5b were also
obtained from the ortho-metalation of o-methoxy phenyl
phosphorodiamidate 1b (Ar = 2-OMe-C6H4), followed by
TMSCl and MeI quench, respectively. To demonstrate the
synthetically very useful synergism of meta-related OMe
DMGs to in-between metalation,20 we studied the meta-
methoxy phenyl phosphorodiamidate 1c (Ar = 3-OMe-C6H4).
In this event, under these metalation conditions, followed by
MeI and I2 quench, compound 1c afforded exclusively 6a and
6b, respectively, in high yields.
We next explored the competitive DoM and lateral
metalation capabilities of the OP(O)(NEt2)2 DMG in the
context of other previously studied DMGs. Watanabe and co-
workers had shown that various substituted ortho-tolyl
OP(O)(NMe2)2 substrates 9 undergo highly selective lateral
metalation and subsequent electrophile quench, even at −105
°C, to afford the corresponding ortho-alkyl substituted
products 10 (E = various) in good yields (see Scheme 3).11a
Scheme 3. Lateral Metalation of Watanabe’s ortho-Tolyl
Tetramethylphosphorodiamidate 9
B
https://dx.doi.org/10.1021/acs.orglett.0c00094
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
pubs.acs.org/OrgLett
Letter
Since neither the work of Watanabe11 nor the work of
Melvin7 and Dhawan10 had reported the vinylogous phospha
AoF rearrangement on tetramethylphosphorodiamidate 9 (R =
H), we also tested this reaction by initial deprotonation with
LDA at −78 °C, followed by warming to 0 °C. The
observation of an LDA-mediated cleavage to give phenol 11
in high yield predicts that the more sterically demanding
tetraethylphosphorodiamidate group was required for the
desired reaction to occur.
give compound 14 in high yield, while the corresponding
phosphorodiamidate 5b, under the same conditions (s-BuLi/
THF/−78 °C), underwent a sluggish reaction at rt and, even
upon heating to 60 °C, did not give product 13. This was
surprising because lateral metalation of 5b was demonstrated
by a CD3OD quench experiment at −78 °C to give 5b′ in
quantitative yield with >95% deuterium incorporation.
However, change of base to a mixture of LDA/TMEDA (3
equiv) at 25 °C in hexanes effected the migration reaction to
give 13 in 87% yield. Parenthetically, the benzylic phospho-
namide 13 and phosphonate 14 constitute potentially useful
intermediates in Corey’s protocol for the preparation of
olefins.22
As a result, we turned our attention to the discovery of the
lateral metalation reaction of compound 5b and, for
comparison, that of phosphate 12 (see Scheme 4). Both
Scheme 4. Lateral Metalation of
A more-complex reaction ensued for the prototype ortho-
tolyl phosphorodiamidate 4d, which led us to perform a series
of metalation−deuteration experiments on compound 4d, as a
function of base concentration, time, and temperature of
reaction (see Table 1). A brief reaction time (to approximate
kinetic control conditions) with 1.1 equiv of s-BuLi yielded
incomplete (50%) but mostly lateral metalation of 4d (15:16 =
50:3; see Table 1, entry 1), a preference also observed when
the reaction proceeded extensively using a standard metalation
time (15:16 = 70:23; see Table 1, entry 2). Nevertheless, while
4B undergoes phospha AoF rearrangement to 18 upon
warming to rt (Table 1, entry 3), the major anion 4C, in
agreement with the behavior of 5b, as discussed earlier, escapes
the similar vinylogous process and is reprotonated to 4d
(Table 1, entry 3). When using 2.1 equiv of s-BuLi (Table 1,
entries 4 and 5), the formation of dianion 4A may be expected
but cannot be proved, because its dideuterated product
resulting from CD3OD quench cannot be distinguished from
a mixture of 15 and 16.23a The product 17 (Table 1, entry 4) is
unlikely the result of initial anionic phospha-Fries rearrange-
ment, followed by lateral metalation−deuteration, because the
acidity of the benzylic hydrogens would be decreased by
phenolate resonance. Instead, its presence supports the
formation of the dianion species 4A.23b The absence of 4d
Tetraethylphosphorodiamidate 5b and Diethyl Phosphate
12
reactions are analogues of the lateral metalation−carbamoyl
migration process of o-tolyl O-carbamates previously estab-
lished in our laboratories.4e In the event, both 12 and 5b
underwent metalation−migration but with strikingly different
migratory aptitudes. Thus, ortho-tolyl phosphate 12 (R = OEt)
underwent a 1,4-O → C phosphoryl migration smoothly to
Table 1. DoM and Phospha-Fries Rearrangement of ortho-Tolyl Tetraethylphosphorodiamidate 4d
b
Conditions
Product Ratio
a
No.
s-BuLi (equiv)
time
quench
E
15
16
17
18
4d
c
1
2
3
4
5
1.1
1.1
1.1
2.1
2.1
7 min
1 h
1 h → rt
1 h → rt
1 h → rt
CD3OD
CD3OD
NH4Cl
CD3OD
NH4Cl
D
D
H
D
H
50
70
−
−
−
3
23
−
−
−
−
−
−
72
−
−
−
20
47
7
80
−
−
c
d
d
28
95
d
e
a
b
c
d
e
1
s-BuLi added at −78 °C. Ratios measured by H NMR. Quench at −78 °C. Quench at rt. 75% yield of isolated product.
C
https://dx.doi.org/10.1021/acs.orglett.0c00094
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
pubs.acs.org/OrgLett
Letter
(Table 1, entry 5) in the product mixtures suggests that, when
using 2.1 equiv of s-BuLi, the initial mixture of 4B and 4C
undergoes further ortho-metalation to afford a mixture of
monoanions and dianions 4A and 4B, both species undergoing
phospha-AoF rearrangement as the temperature increases,
forming the same product 18.
AUTHOR INFORMATION
Corresponding Author
■
Victor Snieckus − Department of Chemistry, Queen’s University,
Kingston K7L 3N6, ON, Canada; orcid.org/0000-0002-
6448-9832; Email: snieckus@chem.queensu.ca
We also addressed the important question of the DoM
reactivity hierarchical positions of the powerful OCONEt2
DMG1a,4b vs OP(O)(NEt2)2 DMG. An intermolecular
competition experiment was performed by metalating an
equimolar mixture of 1a and 19 with only half the
stoichiometric amount of s-BuLi (Scheme 5). After stirring
Authors
Manlio Alessi − Department of Chemistry, Queen’s University,
Kingston K7L 3N6, ON, Canada
Jignesh J. Patel − Department of Chemistry, Queen’s University,
Kingston K7L 3N6, ON, Canada
Kristina Zumbansen − Department of Chemistry, Queen’s
University, Kingston K7L 3N6, ON, Canada
Scheme 5. Comparison of DMG Strengths:
Complete contact information is available at:
https://pubs.acs.org/10.1021/acs.orglett.0c00094
Phosphorodiamidate 1a versus O-Carbamate 19
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
We are grateful to NSERC for support under the Discovery
Grant program and to Dr. Franco
Chemistry, Queen’s University) for NMR expertise.
■
̧
ise Sauriol (Department of
for 1 h at −78 °C, the reaction mixture was quenched at −78
°C with excess of CD3OD, allowed to warm to 0 °C, and the
products were separated and analyzed to reveal 1a′ (50% yield,
>95% d1-content), 19′ (38% yield, >95% d1-content) and 6%
of the AoF rearrangement product 20 (see the Supporting
Information for details). With the appropriate caveat of
interpretation of competition experiments,1a the outcome of
this experiment implies not only that the OP(O)(NEt2)2
stands in close rank to the OCONEt2 group as the most
powerful DMG3c but also that the former is more stable than
the latter toward the AoF rearrangement reaction.24
In conclusion, the power of the OPO(NEt2)2 DMG in DoM
chemistry has been demonstrated by the development of a
general and efficient synthesis of ortho-substituted aryl O-
phosphorodiamidates (see Scheme 1). The choice of the
OPO(NEt2)2 over the corresponding OPO(NMe2)2 DMG
allows the use of the more practical typical DoM temperatures
(−78 °C) over the previously reported −105 °C conditions. In
addition, the phospha-AoF rearrangement leading to ortho-
phosphonic diamide phenol has been established (see Scheme
2). The metalation−deuteration chemistry of ortho-tolyl
OPO(NEt2)2 derivatives has been studied under a variety of
conditions (Table 1) and offers methodology for the synthesis
of corresponding contiguously substituted benzyl phosphonic
diamides and esters (see Scheme 4). As suggested by
intermolecular competition experiments, the directing power
of the OPO(NEt2)2 group is comparable to that of the
OCONEt2 group (see Scheme 5). The present work,
combined with the accompanying study,14 constitutes a
contribution whose value and application to the field of
synthetic aromatic organophosphorus chemistry may be
anticipated.
REFERENCES
■
(1) (a) Snieckus. Chem. Rev. 1990, 90, 879−933. (b) Hartung, C.;
Snieckus, V. In Modern Arene Chemistry; Astruc, D., Ed.; Wiley−VCH:
Weinheim, Germany, 2002; pp 330−367. (c) Anctil, E. J. G.;
Snieckus, V. In Metal-Catalyzed Cross-Coupling Reactions, 2nd Edition;
Diederich, F., de Meijere, A., Eds.; Wiley−VCH: Weinhiem,
Germany, 2004, 761−813. (d) Macklin, T.; Snieckus, V. In Handbook
of C−H Transformations, Vol. 1; Dyker, G., Ed.; Wiley−VCH:
Weinheim, Germany, 2005; pp 106−118. (e) Board, J.; Cosman, J. L.;
Rantanen, T.; Singh, S.; Snieckus, V. Platinum Met. Rev. 2013, 57, 234.
(2) Other valuable O-based DMGs have been reported. For
OMOM, see: (a) Christensen, H. Synth. Commun. 1975, 5, 65−78.
For OTHP, see: (b) Harris, T. D.; Oruganti, S. R.; Davis, L. M.;
Keehn, P. M.; Green, B. S. Tetrahedron 1987, 43, 1519−1540. Azzouz,
R.; Bischoff, L.; Fruit, C.; Marsais, F. Synlett 2006, 2006, 1908−1912.
For OSEM, see: (c) Sengupta, S.; Snieckus, V. Tetrahedron Lett. 1990,
31, 4267−4270.
(3) For original work, see: (a) Nerdinger, S.; Kendall, C.; Cai, X.;
Marchart, R.; Riebel, P.; Johnson, M. R.; Yin, C.-F.; Eltis, L. D.;
Snieckus, V. J. Org. Chem. 2007, 72, 5960−5967. For recent studies,
see: (b) Lira, R.; Xiang, A. X.; Doundoulakis, T.; Biller, W.; Agrios, K.
A.; Simonsen, K. B.; Webber, S. E.; Sisson, W.; Aust, R. M.; Shah, A.
M.; Showalter, R. E.; Banh, V. N.; Steffy, K. R.; Appleman, J. R.
Bioorg. Med. Chem. Lett. 2007, 17, 6797−6800. (c) Zhou, J.; Lobera,
M.; Neubert-Langille, B. J.; Snider, B. B. Tetrahedron 2007, 63,
10018−10024. For a comprehensive tabular up-to-date summary of
O-DMGs and their ranking order, see: (c) Miah, M. A. J.; Sibi, M. P.;
Chattopadhyay, S.; Familoni, O. B.; Snieckus, V. Eur. J. Org. Chem.
2018, 2018, 440−446.
(4) (a) See ref 1a. (b) Miah, M. A. J.; Sibi, M. P.; Chattopadhyay,
S.; Familoni, O. B.; Snieckus, V. Eur. J. Org. Chem. 2018, 2018, 447−
454. OCONR2 AoF rearrangement; see: (c) Sibi, M. P.; Snieckus, V.
J. Org. Chem. 1983, 48, 1935−1937. For application in total synthesis,
see: (d) Macklin, T. K.; Reed, M. A.; Snieckus, V. Eur. J. Org. Chem.
2008, 2008, 1507−1509. For vinylogous AoF rearrangement and
synthesis of benzofuranones, see: (e) Kalinin, A. V.; Miah, M. A. J.;
Chattopadhyay, S.; Tsukazaki, M.; Wicki, M.; Nguen, T.; Coelho, A.
L.; Kerr, M.; Snieckus, V. Synlett 1997, 1997, 839−841. For remote
AoF rearrangement and the synthesis of dibenzopyranones, see:
(f) Wang, W.; Snieckus, V. J. Org. Chem. 1992, 57, 424−426. For
OCON(Me)Cumyl, see: (g) Metallinos, C.; Nerdinger, S.; Snieckus,
ASSOCIATED CONTENT
* Supporting Information
■
sı
The Supporting Information is available free of charge at
https://pubs.acs.org/doi/10.1021/acs.orglett.0c00094.
Full experimental details, 1H and 13C NMR spectra
(PDF)
D
https://dx.doi.org/10.1021/acs.orglett.0c00094
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
pubs.acs.org/OrgLett
Letter
V. Org. Lett. 1999, 1, 1183−1186. For OCON(TMS)-i-Pr, see:
(h) Kauch, M.; Hoppe, D. Can. J. Chem. 2001, 79, 1736−1746. For
1,5-O → N carbamoyl translocation, see: (i) Feberero, C.; Suarez-
Pantiga, S.; Cabello, Z.; Sanz, R. Org. Lett. 2018, 20, 2437−2440. For
carbamoyl Baker−Venkataraman reaction, a synthesis of chrome-
nones occurs. See: (j) Kalinin, A. V.; da Silva, A. J. M.; Lopes, C. C.;
Lopes, R. S. C.; Snieckus, V. Tetrahedron Lett. 1998, 39, 4995−4998.
For a recent excellent comprehensive review on AoF rearrangement,
see: (k) Korb, M.; Lang, H. Chem. Soc. Rev. 2019, 48, 2829−2882.
(5) Morin, J.; Zhao, Y.; Snieckus, V. Org. Lett. 2013, 15, 4102−4105.
(6) Regarding Kumada−Corriu cross coupling, see: (a) Sengupta, S.;
Leite, M.; Raslan, D. S.; Quesnelle, C.; Snieckus, V. J. Org. Chem.
1992, 57, 4066−4068. Quesnelle, C. A.; Snieckus, V. Synthesis 2018,
50, 4395−4412. Chemla, F.; Ferreira, F.; Perez-Luna, A.; Micouin, L.;
Jackowski, O. In Metal-Catalyzed Cross-Coupling Reactions and More;
de Meijere, A.; Brase, S.; Oestreich, M., Eds.; Wiley−VCH::
Weinheim, Germany, 2014; p 365. Regarding Suzuki−Miyaura
cross coupling, see: (b) Quasdorf, K. W.; Antoft-Finch, A.; Liu, P.;
Silberstein, A. L.; Komaromi, A.; Blackburn, T.; Ramgren, S. D.;
Houk, K. N.; Snieckus, V.; Garg, N. K. J. Am. Chem. Soc. 2011, 133,
6352−6363.
the meta-related OPO(NMe2)2 vs OMe combination undergoes in-
between metalation−methylation to afford product in 75% yield, but
this sequence must be performed at −105 °C. (e) For OP(O)(OEt)2,
Melvin also showed in-between metalation at −78 °C, followed by
phospha-AoF at 0 °C in 95% yield (see ref 9). (f) Knochel reported
that aryl OP(O)(NMe2)2 derivatives bearing meta-F, -Br, and -I
groups undergo magnesiation−iodine electrophile quench to afford
mixtures of 2- and 6-substituted products, see ref 15.
(21) Groom, K.; Hussain, S. M.; Morin, J.; Nilewski, C.; Rantanen,
T.; Snieckus, V. Org. Lett. 2014, 16, 2378−2381.
(22) (a) Corey, E. J.; Kwiatkowski, G. T. J. Am. Chem. Soc. 1966, 88,
5652−5653. (b) Corey, E. J.; Kwiatkowski, G. T. J. Am. Chem. Soc.
1968, 90, 6816−6821. (c) Corey, E. J.; Cane, D. E. J. Org. Chem.
1969, 34, 3053−3057.
1
(23) (a) Neither H NMR nor MS analysis gave distinguishable
peaks for integration, see SI. (b) From the product ratio 17:18 = ∼
2:1, it may be deduced that under 2.0 equiv of s-BuLi at −78 °C → rt
conditions, substrate is converted to 4A (72%) and 4B (28%) which,
since 4A requires double the amount of base, indicates consumption
of 1.65 equiv of the original 2.1 equiv of s-BuLi.
(24) In concurrence with our results, intermolecular competition
experiments at −105°C carried out by Watanabe established that the
OP(O)(NMe2)2 is approximately three- to four-fold stronger than the
OMOM, OCONEt2 and CONEt2 DMGs; see refs 13a and 13c.
(7) Melvin, L. S. Tetrahedron Lett. 1981, 22, 3375−3376.
(8) Cambie, R. C.; Palmer, B. D. Aust. J. Chem. 1982, 35, 827−837.
(9) Jardine, A. M.; Vather, S. M.; Modro, T. J. Org. Chem. 1988, 53,
3983−3985.
(10) (a) Dhawan, D.; Redmore, D. J. Org. Chem. 1984, 49, 4018−
4021. (b) Dhawan, D.; Redmore, D. J. Org. Chem. 1986, 51, 179−183.
(11) For reports of the use of OPO(NMe2)2 as DMG, see:
(a) Watanabe, M.; Date, M.; Kawanishi, K.; Tsukazaki, M.; Furukawa,
S. Chem. Pharm. Bull. 1989, 37, 2564−2566. (b) Date, M.; Kawanishi,
K.; Hori, T.; Watanabe, M.; Furukawa, S. Chem. Pharm. Bull. 1989,
37, 2884−2886. (c) Watanabe, M.; Date, M.; Kawanishi, K.; Hori, T.;
Furukawa, S. Chem. Pharm. Bull. 1990, 38, 2637−2643. (d) Watanabe,
M.; Date, M.; Kawanishi, K.; Hori, T.; Furukawa, S. Chem. Pharm.
Bull. 1991, 39, 41−48.
(12) (a) Legrand, O.; Brunel, J. M.; Constantieux, T.; Buono, G.
Chem. - Eur. J. 1998, 4, 1061−1067. (c) Legrand, O.; Brunel, J. M.;
Buono, G. Buono, G. Eur. J. Org. Chem. 1999, 1999, 1099−1105.
(d) Legrand, O.; Brunel, J. M.; Buono, G. Tetrahedron 2000, 56, 595−
603.
(13) (a) Clososki, G. C.; Rohbogner, C. J.; Knochel, P. Angew.
Chem., Int. Ed. 2007, 46, 7681−7684. (b) Rohbogner, C. J.; Clososki,
G. C.; Knochel, P. Angew. Chem., Int. Ed. 2008, 47, 1503−1507.
(c) Rohbogner, C. J.; Wirth, S.; Knochel, P. Org. Lett. 2010, 12,
1984−1987. For a recent study on a heterocyclic system, see:
Balkenhohl, M.; Heinz, B.; Abegg, T.; Knochel, P. Org. Lett. 2018, 20,
8057−8060.
(14) Blackburn, T.; Patel, J. J.; Alessi, M.; Snieckus, V. Org. Lett.
2020 accompanying Letter.
(15) For a sampling of significance as antioxidants, biologically active
molecules, and agrochemicals, see: (a) Toshiyuki, K.; Yoshinobu, S.;
Hironori, Y.; Kiyotaka, S. International Patent No. WO 2006126393,
2006. Feng, L.; Anbin, T.; Zigui, X.; Shiwen, L. Can. Patent No. CN
100999145, 2007. For use as flame retardants, see: (b) Qureshi, A.;
Hay, A. S. J. Chem. Res., Synop. 1998, 355. Keglevich, G.; Szelke, H.;
́
́
Kerenyi, A.; Kudar, V.; Hanusz, M.; Simon, K.; Imre, T.; Ludanyi, K.
Tetrahedron: Asymmetry 2005, 16, 4015−4021.
(16) Beak, P.; Brown, R. A. J. Org. Chem. 1977, 42, 1823−1824.
(17) Comins, D. L.; Brown, J. D. J. Org. Chem. 1986, 51, 3566−
3572.
(18) Cuevas, J.-C.; Patil, P.; Snieckus, V. Tetrahedron Lett. 1989, 30,
5841−5844.
(19) This compound can also be prepared in one step from POCl3.
See: Lyttle, M. H.; Satyam, A.; Hocker, D. M.; Bauer, K. E.; Caldwell,
C. G.; Hui, H. C.; Morgan, A. S.; Mergia, A.; Kauvar, L. M. J. Med.
Chem. 1994, 37, 1501−1507.
(20) For OMOM: (a) Winkle, M. R.; Ronald, R. C. J. Org. Chem.
1982, 47, 2101−2108. (b) For OCONEt2, see ref 4c. (c) For
CONEt2, see ref 4b. (d) For OPO(NMe2)2, Watanabe showed that
E
https://dx.doi.org/10.1021/acs.orglett.0c00094
Org. Lett. XXXX, XXX, XXX−XXX