Rhodium(II)-catalyzed asymmetric sulfur(VI) reduction of diazo sulfonylamidines

Article abstract of DOI:10.1021/ja210180q

Diazo sulfonylamidines readily undergo enantioselective oxygen transfer from sulfur to carbon atom in the presence of chiral rhodium(II) carboxylates resulting in chiral sulfinylamidines. This unusual asymmetric atom transfer "reduction" occurs rapidly under mild conditions, and sulfinylamidines are obtained in excellent yield.

Full text of DOI:10.1021/ja210180q

Communication
pubs.acs.org/JACS
Rhodium(II)-Catalyzed Asymmetric Sulfur(VI) Reduction of Diazo
Sulfonylamidines
Nicklas Selander and Valery V. Fokin*
The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, United States
S
* Supporting Information
variety of amino-substituted adducts from the corresponding
sulfonyl azides (6) and ynamines (7).5 Although tautomers 8
and 9 may exist in equilibrium,5c we found that the diazo
amidine chain form 9 was the dominant tautomer (eq 2; see
Supporting Information for details).
ABSTRACT: Diazo sulfonylamidines readily undergo
enantioselective oxygen transfer from sulfur to carbon
atom in the presence of chiral rhodium(II) carboxylates
resulting in chiral sulfinylamidines. This unusual asym-
metric atom transfer “reduction” occurs rapidly under mild
conditions, and sulfinylamidines are obtained in excellent
yield.
hiral sulfinyl imines and sulfinamides are versatile
C
intermediates and ligands in asymmetric synthesis.1 As
is the case for most chiral sulfur(IV) compounds, their
preparation involves asymmetric oxidation of sulfur(II) starting
materials. In this communication, we wish to report an
unprecedented asymmetric formal reduction of sulfur(VI) in
sulfonylamidines to sulfur(IV), leading to enantioenriched
sulfinylamidines.
Our initial studies employing the diazo sulfonylamidines 9 in
the rhodium-catalyzed cyclopropanation of styrene gave no
traces of the cyclopropane products. Instead, we observed rapid
evolution of dinitrogen and selective formation of sulfinylami-
dines 11 (eq 3).
We have recently demonstrated the synthetic utility of 1-
sulfonyl 1,2,3-triazoles (1) as stable and versatile progenitors of
azavinyl carbenes. A clear advantage of this chemistry is the
ability to access novel carbene intermediates without the need
to prepare and isolate diazo compounds. The rhodium carbene
intermediates (2) generated in situ from the sulfonyl triazoles,
have been applied in highly enantioselective cyclopropanation
of olefins (3),2 transannulation with nitriles (4),3 and in the
alkane C−H insertion reactions (5),4 thus expanding the
repertoire of transformations of diazo compounds (eq 1).
Only a few examples of uncatalyzed intramolecular reactions
of the sulfonyl functionality with diazo compounds have been
described in the literature.6 However, the known reactions were
slow (up to 3 days) and did not involve any transition metal
catalysts. We found that in the presence of rhodium carboxylate
catalysts, this reaction proceeded to completion within minutes
at 0 °C. As the transfer of the oxygen atom from the sulfonyl
group to the diazo carbon creates a chiral sulfur center, we
envisioned that chiral rhodium carboxylates might render this
reaction asymmetric.
Examination of a series of catalysts shown under Table 1
confirmed this hypothesis. Thus, sulfinylamidine 11a was
obtained in nearly quantitative yield with only 1 mol % of the
rhodium catalyst. When chiral carboxylates were used, we
found that the transfer of the oxygen atom was indeed
stereoselective. Although only modest ee, 27%, was obtained
7
4
using Muller’s Rh (S-NTTL) catalyst (Table 1, entry 1),
̈
2
rhodium carboxylates containing more sterically encumbered
substituents led to improved enantioselectivity (entries 1−4). A
racemic mixture of the product was obtained using the Rh2(S-
PTV)4 catalyst, whereas the bulkier Rh2(S-PTTL)48 and Rh2(S-
Since the stability of the triazole ring is affected by the
substituents at the N1, C4, and C5 atoms of the heterocycle, we
turned our attention to 1-sulfonyl-5-dialkylamino 1,2,3-triazoles
(8). We envisioned that the amino substituent at C5 would
stabilize the open chain diazo amidine form, giving rise to novel
azavinyl carbene species (10). To this end, we prepared a
Received: October 29, 2011
Published: January 10, 2012
© 2012 American Chemical Society
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Communication
a
a
Table 1. Rh-Catalyzed Synthesis of Chiral Sulfinylamidines
Table 2. Reactivity of Various Diazo Sulfonylamidines
a
One milliliter solution of 9a (0.15 mmol) was added dropwise to a 1
mL solution of the catalyst (1 mol %).
9
PTAD)4 catalysts gave 42% and 57% ee, respectively. In
addition, the tetrachloro-substituted Rh2(S-TCPTTL)4 catalyst
led to a slight further improvement of the ee (62%). No
induction of chirality was observed in the presence of Rh2(S-
a
Two milliliter solution of 9 (0.50 mmol) was added dropwise to a 2
b
mL solution of the catalyst (0.5 mol %). Reaction carried out for 90
min.
10
DOSP),4 and no reaction occurred when carboxamidate
11
Rh2(4S-MPPIM)4 was used.
deactivation was observed in this case. Increasing the steric bulk
at sulfur resulted in a significant improvement of the ee, 96%
for 11e and 87% for 11f, with consistently high yields. High
enantioselectivity was also observed for ortho-functionalized
aromatic substituents on sulfur. Sulfinylamidine 11g was
isolated in 95% yield with 89% ee, whereas an electron-
withdrawing group in the ortho position led to a drop in ee
(80% for 11h). Alkyl-substituted sulfonylamidine was equally
reactive, although the product 11i was obtained with a lower
enantioselectivity (ee 44%).
A slight increase in ee was observed when the dimethyl
amine group was replaced with the diethyl amine (cf. 57% for
11a and 64% for 11j). A similar ee, 66%, was observed for 11k,
however, this reaction required 90 min to proceed to
completion. Finally, the aromatic group attached to the diazo
carbon was modified. We found that an electron withdrawing
para-substituent gave 67% ee (11m), while an electron
Reactions performed in other solvents (DCM, 1,2-DCE, and
toluene; entries 8−10) resulted in a slightly lower enantiose-
lectivity, although the yield of 11a remained excellent. It is
noteworthy that the reaction also proceeded in high yield in
methanol at elevated temperature, but enantioselectivity was
lost (entry 11). This experiment points to the facility of this
intramolecular process.
Using chloroform and 0.5 mol % of the commercially
available Rh2(S-PTAD)4 catalyst, we then investigated the
scope of the reaction with respect to various sulfonylamidines
(Table 2). The 4-halogenated benzene sulfonyl amidines
resulted in similar enantioselectivities, 11a (57%) and 11b
(56%). Tosyl amidine led to a slight improvement of
enantioselectivity (65% ee, 11c). Interestingly, the reaction
also proceeded in high yield in the presence of amide
substituents, albeit with a lower ee value (11d). No insertion
of the rhodium carbene into the N−H bond or catalyst
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Communication
donating group led to a lower ee value, 51% for 11l (cf. 57% for
11a). Furthermore, the ortho-substituted 11n reacted very
slowly: after 10 h, less than 5% conversion was observed,
indicating either an unfavorable electronic interaction and/or
too bulky environment for the formation of the corresponding
Rh-carbene.
Scheme 1. Proposed Catalytic Cycle
The very short reaction times and high yields obtained under
mild conditions clearly demonstrate the facility of the
intramolecular reduction of sulfur compared to those obtained
with other intra- and intermolecular processes, such as C−H,
N−H, or O−H insertions, carbene dimerization, or cyclo-
propanation. The reaction also took place in the presence of a
variety of substituents with different steric and electronic
properties. A probable explanation for the observed reactivity
was unveiled by examination of the data from single-crystal X-
sulfonyl oxygen atom is facilitated by the electron-rich
dialkylamine substituent and the dirhodium moiety, which
acts as an “electron sink”, yielding intermediate 12. The
enantioselectivity of the process is determined by the geometry
of intermediate 10, favoring attack by one of the oxygen atoms
in favor of the other. Decomposition of intermediate 12
regenerates the rhodium catalyst and delivers chiral product 11.
In addition to providing a practical synthesis of enantioen-
riched sulfinylamidines, this work demonstrates that rhodium
azavinyl carbenes are sufficiently electrophilic to effect an
unexpected oxygen transfer from the thermodynamically stable
and generally considered inert sulfonamide sulfur(VI) atom.
The role of dirhodium carboxylates in this transformation is
two-fold: in addition to catalyzing decomposition of the diazo
amidine, the dirhodium center acts as an electron buffer which
orchestrates a complex sequence of bond-forming events. The
facility, experimental simplicity, and high yields and good to
excellent enantioselectivity make this newly discovered trans-
formation a convenient method for the synthesis of densely
functionalized sulfinylamidine derivatives and a useful reactivity
probe for studying other heteroatom transfer reactions
involving metal-stabilized carbenes.
ASSOCIATED CONTENT
■
Figure 1. Crystal Structures of 9a and 11a.
S
* Supporting Information
Experimental procedures, characterization data, NMR spectra,
and crystallographic data. This material is available free of
charge via the Internet at http://pubs.acs.org.
ray crystallographic analysis of compounds 9a and 11a (Figure
1).
The most intriguing feature of structure 9a is the close
proximity and the spatial alignment of the sulfonyl oxygen
atoms (3.113 Å and 3.165 Å, respectively) with respect to the
diazo carbon. The short distance between the oxygen atom and
the latent carbene center, in addition to the electron-donating
character of the dialkylamino substituent, provides a logical
explanation of the unexpectedly fast intramolecular oxygen
transfer. Furthermore, the exclusive E-geometry of the amidine
bond in 9a may influence the outcome of the reaction. It is
important to point out that the intramolecular oxygen atom
transfer was not observed at all in our previous studies of Rh-
carbenes 2 generated from 1-sulfonyl 1,2,3-triazoles (1) lacking
the 5-amino substituent.2−4 In the latter system, the sulfonyl
group in the azavinyl carbene is likely pointing away from the
carbene center (cf. structures 2 in eq 1 and 9a in Figure 1).
We hypothesize that the intramolecular reaction described
here proceeds via the intermediates shown in Scheme 1. It
begins with a rapid formation of rhodium carbene 10 from the
diazo amidine 9. Attack at the electrophilic carbene center by a
AUTHOR INFORMATION
■
Corresponding Author
fokin@scripps.edu
ACKNOWLEDGMENTS
■
This work was supported by the National Science Foundation
(CHE-0848982). N.S. also acknowledges a postdoctoral
fellowship from the Swedish Research Council (VR).
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