Stereoselective 1,3-insertions of rhodium(II) azavinyl carbenes

Article abstract of DOI:10.1021/ja408185c

Rhodium(II) azavinyl carbenes, conveniently generated from 1-sulfonyl-1,2,3-triazoles, undergo a facile, mild, and convergent formal 1,3-insertion into N-H and O-H bonds of primary and secondary amides, various alcohols, and carboxylic acids to afford a wide range of vicinally bisfunctionalized (Z)-olefins with perfect regio- and stereoselectivity. Utilizing the distinctive functionality installed through these reactions, a number of subsequent rearrangements and cyclizations expand the repertoire of valuable organic building blocks constructed by reactions of transition-metal carbene complexes, including α-allenyl ketones and amino-substituted heterocycles.

Full text of DOI:10.1021/ja408185c

Article
pubs.acs.org/JACS
Stereoselective 1,3-Insertions of Rhodium(II) Azavinyl Carbenes
Stepan Chuprakov, Brady T. Worrell, Nicklas Selander, Rakesh K. Sit, and Valery V. Fokin*
Department of Chemistry, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, United States
*
S Supporting Information
ABSTRACT: Rhodium(II) azavinyl carbenes, conveniently
generated from 1-sulfonyl-1,2,3-triazoles, undergo a facile,
mild, and convergent formal 1,3-insertion into N−H and O−H
bonds of primary and secondary amides, various alcohols, and
carboxylic acids to afford a wide range of vicinally
bisfunctionalized (Z)-olefins with perfect regio- and stereo-
selectivity. Utilizing the distinctive functionality installed
through these reactions, a number of subsequent rearrange-
ments and cyclizations expand the repertoire of valuable
organic building blocks constructed by reactions of transition-
metal carbene complexes, including α-allenyl ketones and
amino-substituted heterocycles.
5
INTRODUCTION
sulfonyl azides and terminal alkynes (eq 2). 1-Sulfonyltriazoles
1
■
6
exist in equilibrium with their diazoimine tautomers 1′,
Transition-metal-catalyzed reactions of diazo compounds are
powerful methods for the formation of carbon−carbon and
carbon−heteroatom bonds via additions and insertions of
which can be efficiently intercepted by transition-metal catalysts
to give rise to highly reactive rhodium(II) azavinyl carbenes 2
(eq 3). Although these intermediates share many features with
the well-known donor−acceptor carbenes obtained from
1
highly reactive metal carbene intermediates. Thus, rhodium-
(
II) and copper(I) carbenes derived from α-diazocarbonyl
compounds readily undergo 1,1-insertion into N−H and O−H
bonds to afford easy access to α-amino or α-oxy derivatives of
7
2 3
diazocarbonyl compounds (eq 1), the aforementioned
equilibrium and the presence of the aldimine group significantly
alter their reactivity. The ring−chain tautomerism, which
normally favors the ring structure 1, slowly feeds the diazo
imine species in the reaction, thus obviating controlled-addition
requirements and simplifying the experimental setup. The
pendant imine group allows fine-tuning of the steric and
ketones and esters (eq 1).
8
electronic properties of carbene 2. Its reactivity can be further
exploited, for example, in subsequent cyclizations, expanding
the repertoire of molecular architectures available from diazo
compounds. Recent additions to the rapidly growing list of
applications of 1-sulfonyl-1,2,3-triazoles under Rh(II) catalysis
9
include transannulations and cyclopropanations, C−H in-
10
sertion, ketone formation with water and O−H insertions/
1
1
8,12
12a
rearrangements, ring expansions, rearrangement reactions,
13
and arylation with boronic acids. In view of the efficiency of
both the Cu(I)-catalyzed formation of triazole 1 and its
subsequent Rh(II)-catalyzed denitrogenative reactions,
5
8
−13
this
sequence of simple transformations can be viewed as a two-step
regio- and stereoselective bisfunctionalization of the acetylenic
backbone.
We recently reported a highly efficient insertion of Rh(II)
azavinyl carbenes 2 into the C−H bonds of unactivated alkanes
1
0a
(
eq 3). This 1,1-insertion likely proceeds via a direct hydride
10b
abstraction involving a three-membered transition state. In
contrast, because of the polarized nature of N−H and O−H
Certain electron-deficient 1,2,3-triazoles have recently
emerged as convenient progenitors of diazo species. Generally
4
stable, crystalline compounds, they are easily prepared under
mild copper(I)-catalyzed conditions from the corresponding
Received: August 7, 2013
©
XXXX American Chemical Society
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bonds, we expected that they would react with azavinyl carbene
1
2
through a different insertion pathway. For example, it has
previously been proposed that insertion of rhodium carbenes
derived from diazo ketones or esters into O−H bonds may
proceed via the formation of an ylide intermediate followed by
intra- or intermolecular proton abstraction, resulting in the
overall 1,1-insertion (eq 1). As evidenced by previous work,
products derived from azavinyl carbenes 2 are often isolated in
the stable enamide tautomeric form as opposed to the sulfonyl
1
1−13
imine derivative.
We envisioned that the related insertion
of carbene 2 into O−H and N−H bonds could operate via two
distinct mechanistic pathways (eq 4): (i) a direct 1,1-insertion
followed by tautomerization, which could lead to an isomeric
mixture of enamide products (path a); or (ii) the formation of
ylide intermediate 3 followed by a stereospecific proton transfer
Figure 1. Crystal structure of enamide product 5a.
(
via a presumed hydrogen-bond-stabilized five-membered
Additionally, it was observed that rhodium(II) acetate gave
comparable results to the more soluble rhodium(II) octanoate
catalyst (Table 1, entry 5), but the latter proved to be a superior
catalyst when used in larger-scale reactions (Table 1, entries 6 and 7).
With the optimized conditions (Table 1, entry 7) in hand, we
transition state), which could result in the syn-selective
formation of enamide products (path b). Herein we report a
modular and mild formal 1,3-insertion reaction of rhodium(II)
azavinyl carbenes with various N−H- and O−H-containing
reactants that yields highly functionalized enamide products as
single geometrical isomers. We propose that this insertion reaction
operates through the ylide-mediated mechanism (path b in eq 4),
consistent with the high Z selectivity observed in this process.
15
examined the scope of this N−H insertion reaction. Variously
substituted 1-sulfonyl-1,2,3-triazoles 1 reacted smoothly with an
array of primary amides 4, leading to the substituted (Z)-
enamides 5 with complete stereoselectivity (Table 2). Varying
the electronic or steric nature of the sulfonyl group at N-1 of
triazole 1 did not greatly affect the efficiency of this reaction.
Accordingly, aliphatic and aromatic sulfonyl groups as well as
sulfamoyl derivatives were tolerated in this reaction, giving
excellent yields of products 5a−d (84−95%; Table 2).
RESULTS AND DISCUSSION
■
N−H Insertions with Primary Amides. The distinct
reactivity of rhodium(II) azavinyl carbenes 2 toward N−H
bonds was first observed when 1-mesyltriazole 1a was allowed
to react with 2 equiv of methyl carbamate (4a) in the presence
of 1 mol % Rh(II) octanoate dimer at 65 °C (Table 1, entry 1).
As Table 2 illustrates, a number of carbamates were effective
in the formal 1,3-insertion with triazole 1, including halo-
substituted and bulky tert-butyl variants of 4, which gave superb
yields of the corresponding products 5e and 5f (96% and 93%,
respectively). Additionally, alkyl, alkenyl, and aryl amides 4
readily afforded the desired products 5g−I in good yields, while
a number of functional groups (e.g., nitrile and nitro groups)
were tolerated in this reaction. The efficiency of this
transformation was not significantly affected by the nature of
the C-4 aryl group in triazole 1. Thus, substrates with electron-
rich, electron-deficient, or heterocyclic groups gave comparable
yields of the corresponding diamine products (5j−m; Table 2).
Moreover, sulfonamides were also found to undergo facile N−
H insertion to afford the expected 1,2-bis-sulfonamide products
Table 1. N−H Insertion with Primary Amides: Optimization
of the Reaction Conditions
a
b
entry
catalyst
equiv of 4a
solvent
yield (%)
1
2
3
4
5
6
7
Rh (Oct)
2
CHCl3
CHCl3
1,2-DCE
PhMe
90
95
79
0
2
4
4
4
4
Rh (Oct)
2
1.1
1.1
1.1
1.1
1.1
1.1
Rh (Oct)
2
5
n−r in good yields. Remarkably, the structurally complex
Rh (Oct)
2
Celecoxib analogue was shown to furnish the desired N−H
insertion product 5p in excellent yield (91%) despite bearing a
pendent basic nitrogen atom.
Rh (OAc)
2
CHCl3
CHCl3
CHCl3
95
4
4
c
Rh (OAc)
2
89
c
Rh (Oct)
2
95
4
a
The lack of information on these diamine products in the
Conditions: triazole 1a (0.20 mmol), methyl carbamate 4a, and
Rh L (1.0 mol %) in 1 mL of dry CHCl at 65 °C for 30 min in a
16
literature prompted further investigation of their reactivity. In
the course of our studies, we noted that these compounds were
extremely configurationally stable: no isomerization of the
double bond was noted even under forcing conditions.
Furthermore, the configuration of the double bond remained
intact even upon liberation of one of the amino groups: the Boc
group in diamine 5f could be efficiently removed using standard
deprotection treatment with TFA (eq 5). The deprotected amine
could be isolated as a single isomer in excellent yield as the
trifluoroacetate salt 6, which could further undergo hydrogenation,
yielding the saturated diamine salt 7 in similarly good yield (eq 5).
In addition, we found that the catalytic hydrogenation of the
enamide products 5 could be coupled with N−H insertion in
an efficient and operationally simple one-pot procedure to
deliver the saturated diamine 8 in excellent yield (eq 6). This
2
4
3
b
c
microwave reactor. NMR yields, unless otherwise noted. Isolated
yield (1.0 mmol scale).
Direct α-amination (1,1-insertion), similar to that previously
reported for diazoesters reacting with carbamates, was not
observed in the N−H insertion with azavinyl carbenes 2.
Instead, diamine 5a was rapidly formed in high yield as a single
regio- and stereoisomer. The identity of this product was
established by single-crystal X-ray analysis, confirming the Z
2
14
geometry of the double bond (Figure 1).
Optimization of the reaction conditions revealed that the
amount of carbamate 4a could be reduced to only 1.1 equiv
(
Table 1, entry 2), and the use of different organic solvents
(toluene or 1,2-DCE) was not beneficial (Table 1, entries 3 and 4).
B
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,
a b
Table 2. Substrate Scope of the Rh(II)-Catalyzed N−H Insertion of Primary Amides
a
Conditions: 1-sulfonyl-1,2,3-triazole 1 (1.0 mmol), amide 4 (1.1 mmol), and Rh (Oct) (0.01 mmol) in 3 mL of dry CHCl at 75 °C for 1−3 h.
2
4
3
b
c
Isolated yields are shown. 100 °C.
yield of the expected diamine 10a, ketone derivative 11a was
formed in significant quantities (25%; Table 3). We propose
that the formation of ketone 11a arises from an initial O−H
insertion of the azavinyl carbene into the hydroxy tautomer of
9a followed by rearrangement of the putative intermediate 12
(
Table 3). Similarly, reaction of tosyl-substituted triazole 1b
Table 3. Effect of the Rh(II) Catalyst (13a−h) on the
a
Regioselectivity of the Insertion with 2-Oxazolidone
sequential procedure constitutes a simple route to vicinal
diamines, which are valuable organic building blocks and
common structural motifs found in many biologically active
17
natural products, pharmaceuticals, and chiral ligands.
N−H Insertions with Secondary Amides. Having
identified an efficient route to diamine products 5 from
primary amides 4 and triazoles 1, we were naturally interested
in exploring the reactivity of azavinyl carbenes with secondary
amides. Compared with the unsubstituted congeners, secon-
dary amides are more challenging substrates for N−H insertion
reactions because of the presence of only one active N−H bond
and the increased steric demands. In the conventional carbene
reactions using diazocarbonyl compounds, the low activity of
secondary amides or carbamates is usually circumvented by the use
of a large excess of amide, by slow addition of the diazo compound,
or, most commonly, by taking advantage of facile intramolecular
1
insertion into a proximal N−H bond. Given the intrinsically low
a
concentration of the active diazoimine form of triazole 1, in effect
mimicking the high-dilution and large-excess techniques used for
traditional diazocarbonyl compounds, we envisioned that a practical
rhodium(II)-catalyzed intermolecular 1,3-insertion between a
secondary N−H bond and triazole 1 could be achievable.
Conditions: triazole 1 (0.20 mmol), 9a (0.22 mmol), and Rh L
2
4
b
(0.002 mmol) in 1 mL of dry CHCl at 100 °C for 1 h. NMR yields,
unless otherwise noted. Isolated yield (1.0 mmol scale).
3
c
with oxazolidinone 9a under identical reaction conditions
[1 mol % Rh(II) octanoate] provided nearly a 1:1 mixture of
the corresponding N−H and O−H insertion products in
moderate overall yield (Table 3).
To test this possibility, we subjected triazole 1a to reaction
with oxazolidinone 9a in the presence of rhodium(II) octanoate
1
3a in CHCl at 100 °C. To our surprise, along with a 53%
3
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The observed mixture of products (10 and 11) likely
originates from the amide/imidic acid tautomerization
equilibrium of substrate 9a and subsequent competing
formation of O- or N-ylides by the addition of Rh(II) azavinyl
carbenes 2. Therefore, the outcome of the 1,3-insertion
reaction is expected to be determined primarily by the
substrate, namely, the energy barrier of the aforementioned
tautomerization. It has previously been shown that the
electronic character of the carboxylate ligands on the rhodium
complex can greatly bias the reactivity of the Rh carbene, which
often allows for high levels of chemoselectivity (e.g., O−H vs
Table 4. Substrate Scope of the Rh(II)-Catalyzed N−H
,
ab
Insertion of Secondary Amides
1
8
C−H). Taking into account the implicit difference in the
electronic properties of the tautomeric forms of 9a, we
hypothesized that the use of electronically different ligands
on rhodium could improve the selectivity of this reaction.
To this end, we screened a panel of catalysts 13a−h (Figure 2)
in conjunction with both triazoles 1a and 1b to ascertain the
a
General conditions: triazole 1 (1.0 mmol), 9 (1.1 mmol), and Rh2L4
0.005−0.010 mmol) in 4 mL of dry CHCl at 75 °C; (A) Rh -
(
(
3
2
S-NTTL) (13h) 0.5 mol %, (B) Rh (PCC) (13d) 1 mol %, (C)
4
2
4
b
c
Rh (Oct) (13a) 1 mol %. Isolated yields are shown. rt, 36 h.
2
4
d
1
20 °C, 5 h.
Figure 2. Rhodium(II) carboxylate catalysts employed in this study.
parameters affecting the product distribution (Table 3). When
at room temperature and after a prolonged reaction time (36 h)
afforded a good yield of the corresponding N−H insertion
product 10c (Table 4). This product was subjected to single-
crystal X-ray analysis, which confirmed the predicted Z
19
phenylacetic acid-derived catalysts Rh (TPA) (13c) and
2
4
20
Rh (PCC)4 (13d) (Figure 2) were employed with 1-
2
23
mesyltriazole 1a, higher selectivity toward the N−H insertion
product 10a was noted (73% and 79%, respectively; Table 3),
while formation of ketone 11a was suppressed (13% and 7%,
respectively; Table 3).
geometry of the double bond (Figure 3).
Next, the performance of Rh(II) carboxylate complexes
containing amino acid-derived ligands 13e−h (Figure 2) was
21
tested. The catalyst Rh (S-NTTL) (13h) in combination
2
4
with 1-mesyltriazole 1a was found to afford N−H insertion
product 10a in excellent yield and virtually as the exclusive
product of the reaction (>95:5 selectivity). The structurally
related catalyst 13g was only slightly less efficient in the
reaction with 1a, while the electronically similar achiral complex
22
Rh (PTCC) (13e) gave low selectivity and only moderate
2
4
yields of the insertion products (Table 3). The regioselectivity
of the insertion reaction with 1-tosyltriazole 1b was found to be
less responsive to the nature of the Rh(II) catalyst. The most
effective catalyst, Rh (PCC) 13d, afforded only moderate
selectivity toward N−H insertion (∼6:1) but gave a good
overall yield (Table 3).
2
4
Figure 3. Crystal structure of secondary diamine 10c.
The scope of the N−H insertion reaction with secondary
amides under these optimized conditions was examined next.
As expected (vide supra), the selectivity and efficiency of the
reaction were highly dependent on the nature of the amide
partner (Table 4). Thus, the reaction of 1-mesyltriazole 1a with
Interestingly, competing formation of the O−H insertion
product was never observed with a thiolactone-containing
acetamide substrate regardless of the catalyst used (10d, 10f,
9n
10g; Table 4). N-Sulfamoyltriazoles 1, however, required
higher temperatures (100 °C) and the more stable catalyst
Rh (PCC) 13d to ensure a high yield of the 1,3-insertion
N-methylbenzamide in the presence of Rh (S-NTTL)4
2
2
4
produced intractable mixtures of products at elevated temper-
atures (75 °C). However, we found that this substrate reacted
product with this amide substrate (10f, 10g), while
N-mesyltriazole 1a reacted smoothly in the presence of Rh(II)
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octanoate dimer to provide enamide product 10d in good yield
compared with the insertion reaction with isomeric N-
methylbenzamide (10b; Table 3). Likewise, when oxindole,
the cyclic analogue of N-phenylacetamide, was employed,
selective O−H insertion/rearrangement products 11f−h were
formed in high yields (72−93%). Similarly, reactions of 1-
mesyl- and 1-tosyltriazoles 1 with 4-phenylpyridazinone
afforded analogous aminated heterocyclic products 11i−k in
excellent yields (80−97%). In the latter cases, the formation of
a stable heteroaromatic system could be an additional factor
contributing to a higher population of the hydroxy tautomer,
giving rise to the observed selectivity noted with these
substrates.
(
Table 4).
Likewise, it was found that bis-N-Boc-hydrazine and 4-
phenylurazol reacted with different triazoles 1 regioselectively
in the presence of Rh (Oct) , giving exclusively the N−H
2
4
insertion products 10h−j (77−89%; Table 4). Overall, the
electronic character of the C-4 substituent of 1-mesyltriazoles 1
had little to no effect on the reactivity or selectivity in the
reaction with oxazolidinone (cf. 10a and 10e in Table 4).
Another factor contributing to the selectivity of the 1,3-
insertion reaction with secondary amides is the relative steric
hindrance of the −OH and −NH groups. Thus, the 5-phenyl-
substituted analogue of oxazolidinone 9a smoothly underwent
exclusive O−H insertion/rearrangement with 1-mesyltriazole
With the ketone-containing compounds 11i and 11k in hand,
we were intrigued by the possibility of an intramolecular
dehydrative condensation that would lead to unique fused
heterocycles. To this end, 11i and 11k were submitted to acidic
conditions (3:2 H SO /AcOH) at elevated temperature. The
1
a in the presence of catalyst 13a to give ketone 11c in 75%
yield (Table 5). The insertion reaction of 4-(p-methoxyphenyl)-
2
4
Table 5. Substrate Scope of the Rh(II)-Catalyzed O−H
hitherto-unknown desulfonylated pyridazoimidazoles 14a and
14b were formed in excellent yields (86% and 80%,
respectively; eq 7).
,
a b
Insertion of Secondary Amides
O−H Insertions with Carboxylic Acids. We recognized
that the insertion of azavinyl carbenes into O−H bonds of
carboxylic acids could yield intermediates akin to 12 (Table 5);
a subsequent rearrangement would furnish synthetically
appealing N-acyl α-amino ketones. To explore this trans-
formation, we subjected 1-tosyl-1,2,3-triazole 1b to the reaction
with a slight excess of benzoic acid in the presence of 1 mol %
rhodium(II) octanoate dimer 13a in CHCl at 75 °C. To our
3
delight, 2-acyloxyenamine 16a was rapidly formed as a sole,
isolable product in 91% yield (Table 6). Surprisingly, the
Table 6. Rh (Oct) -Catalyzed O−H Insertion with
2
4
,
a b
Carboxylic Acids
a
General conditions: triazole 1 (1.0 mmol), 9 (1.1 mmol), and Rh2L4
0.005−0.010 mmol) in 4 mL of dry CHCl at 75 °C; (A) Rh
(
(
3
2-
S-NTTL) (13h) 0.5 mol %, (B) Rh (PCC) (13d) 1 mol %, (C)
4
2
4
b
c
Rh (Oct) (13a) 1 mol %. Isolated yields are shown. rt, 36 h.
2
4
d
rt, 5 h.
substituted triazole with the same amide was similarly selective,
furnishing the corresponding rearranged product 11d in good
isolated yield. Naturally, the O−H insertion discrimination
observed in these cases, as opposed to the ambiguous selectivity
of the parent carbamate 9a (Table 3), can be attributed to the
increased steric congestion of the N−H bond in the amide
tautomer.
a
General reaction conditions: triazole 1 (1.0 mmol), acid 15
Similar reactivity was noted with N-phenylacetamide;
although the corresponding product 11e was obtained in
poor yield (37% due to instability on silica gel; Table 5), steric
arguments can likely be used to explain the observed exclusive
formation of the O−H insertion product, particularly when
(1.1 mmol), and Rh (Oct) (0.01 mmol) in 3 mL of dry CHCl at
75 °C for 30 min. Isolated yields are shown.
2
4
3
b
anticipated spontaneous rearrangement of product 16a into the
N-acyl α-amino ketone did not occur; further heating or
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treatment with base, acid, or various amine catalysts yielded
only decomposition products. Similar results were obtained
with a number of different carboxylic acids 15 (Table 6). Thus,
pivalic acid, N-Boc-protected proline, and 2-furoic acid were
effective in the O−H insertion with 1-mesyltriazole 1a, giving
excellent yields of the 2-acyloxyenamine products 16c−e,
respectively (75−94%; Table 6).
Table 8. Substrate Scope of the Rh(II)-Catalyzed O−H
,
ab
Insertion with Alcohols and Triphenylsilanol
Next, it was found that the use of less bulky or nonaromatic
carboxylic acids 15 under identical reaction conditions led to
the direct formation of N-acyl α-amino ketones 17 (Table 7).
Table 7. Rh(II)-Catalyzed O−H Insertion/Rearrangement
,
a b
Cascade with Carboxylic Acids
a
General reaction conditions: triazole 1 (1.0 mmol), acid 15
(
7
1.1 mmol), and Rh (Oct) (0.01 mmol) in dry CHCl (3 mL) at
5 °C for 30 min. Isolated yields are shown.
2
4
3
b
a
General reaction conditions: triazole 1 (1.0 mmol), alcohol 18
(
1.1 mmol), and Rh (Oct) (0.01 mmol) in 3 mL of dry CHCl at
2
4
3
b
c
Presumably, the easily accessible primary alkyl-, alkenyl-, or
alkynyl-substituted carbonyl group in the initial O−H insertion
product 16 could rapidly be attacked by the nitrogen atom of
the enamide to furnish the rearranged products 17a−d in good
yields (63−76%; Table 7).
75 °C for 1−5 h. Isolated yields are shown. Catalyst 13b was used
instead of Rh (Oct) . 10 mmol scale.
2 4
d
These valuable electronically rich olefinic building blocks are
not accessible by direct deprotonation/silylation of the
corresponding ketone products because of the presence of
O−H Insertions with Alcohols. As a logical expansion of
our study, we sought to explore simple alcohols as reactive
substrates in 1,3-insertion reactions of rhodium(II) azavinyl
25
the pendant amide moiety.
2
4
carbenes. First, 1-tosyltriazole 1b was tested in the reaction
with ethanol in the presence of the rhodium(II) octanoate
dimer catalyst. While the expected alkoxy enamine was
smoothly formed in high yield as judged by NMR analysis of
the crude mixture, isolation by silica gel chromatography was
problematic because of instability of the product. We
hypothesized that the use of bulkier alcohol reactants could
give more stable and isolable O−H insertion products. Indeed,
treatment of triazole 1b with isopropyl alcohol afforded the
desired alkoxy enamine 19a in good isolated yield (78%; Table 8).
The use of isopropyl alcohol was equally effective with 1-
mesyltriazole 1a, affording product 19b (69%; Table 8). Further
exploration in regard to the scope of effective alcohol components
Interestingly, when propargyl alcohol and triazole 1a were
allowed to react under the standard 1,3-insertion conditions
(vide supra), the usual O−H insertion product was not
observed. Instead, the expected product 21 underwent a
smooth Saucy−Marbet-type [3,3]-sigmatropic rearrangement
to afford α-allenyl ketone 22a in high isolated yield (83%;
26
Table 9). Naturally, we were interested in studying the scope
of this novel cascade, involving formation of the previously
unknown and apparently highly reactive electron-rich prop-
argyloxy enamides 21 en route to versatile and valuable allenyl-
27
containing building blocks.
It was found that a series of variously substituted propargyl
alcohols 20 underwent this O−H insertion/rearrangement
cascade smoothly to afford the corresponding allene products
22b−h in good yields (72−87%; Table 9). Increasing the steric
bulk at the propargyl position of alcohol 20 did not affect the
efficiency of this reaction (22c and 22d; Table 9). Moreover,
internal alkynes bearing either 1-aryl or 1-halo substituents
furnished the corresponding tetrasubstituted allenes in good
yields (22e−g; Table 9). The use of racemic monomethyl
propargyl alcohol 14 afforded allene 22h in high yield, albeit
with moderate diastereoselectivity (dr 73:27). Although the
structures of products 22 were evident from NMR data,
additional confirmation was obtained through single-crystal X-
1
8 revealed that several secondary and tertiary alcohols were
successful in this O−H insertion reaction, efficiently producing the
corresponding alkoxy enamine products 19c−f in good yields
(69−83%; Table 8).
This O−H insertion was also efficient with triphenylsilanol as
a reactant, giving rise to various silyl enol ethers in good yields
(
Table 7). This silanol substrate was found to be effective with
multiple triazoles 1 possessing various aryl groups at the C-4
position (19j−l) as well as with different arylsulfonyl groups at
N-1 (19g−i). Of note, the silyl enol ethers 19 generated by this
1
,3-insertion reaction were formed as single geometrical
28
isomers and are formal descendants of α-amino ketones.
ray analysis of α-allenyl ketone 22e (Figure 4).
F
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Table 9. O−H Insertion/[3,3]-Sigmatropic Rearrangement
versatility of acetylenes and should find applications in the
synthesis of complex molecular architectures.
,
a b
Cascade with Propargyl Alcohols
EXPERIMENTAL SECTION
Typical Preparative Procedure. To a 2−5 mL microwave vial
were added 1-mesyl-4-phenyl-1,2,3-triazole (1a) (0.223 g, 1.0 mmol)
and methyl carbamate (4a) (0.083g, 1.1 mmol), followed by 7.8 mg
■
(
0.01 mmol) of rhodium(II) octanoate dimer 13a. The vial was sealed
with a Teflon microwave cap, and dry CHCl (4.0 mL) was added to
3
the reaction mixture. The vial was stirred at 75 °C in an oil bath for
3
0 min or until the reaction was complete by TLC and LC−MS analysis.
Column chromatography on silica gel using 2:1 ethyl acetate/hexane as the
eluent was directly performed on the reaction mixture to afford 0.257 g
(
0.95 mmol, 95% yield) of (Z)-methyl (2-methylsulfonamido-1-phenylvinyl)-
carbamate (5a) as a colorless crystalline solid.
1
Data for 5a: H NMR (500 MHz, CDCl ): δ 7.53 (d, J = 10.0 Hz,
3
1
(
H), 7.39−7.33 (m, 4H), 7.32−7.28 (m, 1H), 6.40 (bs, 1H), 6.10
s, 1H), 3.80 (s, 3H), 3.10 (s, 3H). 13C NMR (126 MHz, DMSO-d ):
6
δ 154.8, 137.1, 128.3, 126.6, 124.2, 119.4, 117.2, 51.7, 41.1. LRMS
+
(
ESI): m/z 293.2 [M + Na] .
ASSOCIATED CONTENT
* Supporting Information
■
S
Full experimental procedures, characterization data, NMR
spectra, and crystallographic data (CIF). This material is
available free of charge via the Internet at http://pubs.acs.org.
a
General reaction conditions: triazole 1 (1.0 mmol), propargyl alcohol
2
0 (1.1 mmol), and Rh(II) carboxylate (0.01 mmol) in dry CHCl3
AUTHOR INFORMATION
Corresponding Author
fokin@scripps.edu
■
(3 mL) at 75 °C for 0.5−3 h; (A) Rh (Oct) , (B) Rh (Piv) , (C)
2
4
2
4
b
Rh (PCC) . Isolated yields are shown.
2
4
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
This work was supported by the National Institute of General
Medical Sciences, National Institutes of Health (GM-087620)
and the National Science Foundation (CHE-0848982 and
CHE-1302043). N.S. acknowledges a postdoctoral fellowship
from the Swedish Research Council (VR). We also thank Dr.
Arnold L. Rheingold and Dr. Curtis E. Moore for X-ray
analyses.
Figure 4. Crystal structure of α-allenyl ketone 22e.
REFERENCES
■
(
1) Doyle, M. P.; McKervey, M. A.; Ye, T. Modern Catalytic Methods
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CONCLUSIONS
■
(
1
The new family of highly efficient O−H and N−H insertion
reactions of rhodium(II) azavinyl carbenes reported here
exploits the distinct reactivity of these reactive intermediates
directly generated from 1-sulfonyl-1,2,3-triazoles. As opposed
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acceptor carbenes derived from diazocarbonyl precursors, these
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stereoselectively yielding densely functionalized (Z)-enamide
products. The regioselectivity of the 1,3-insertion (N−H vs O−
H) is often determined by the nature of the substrate; however,
it can also be controlled by the catalyst in a number of cases.
The (Z)-enamide products undergo further transformations to
furnish valuable heterocyclic products and building blocks
amenable to further derivatization. These novel and highly
modular methods for regio-, chemo-, and stereoselective bis-
amination and oxyamination of the acetylenic triple bond via
C−N and C−O bond-forming reactions underscore the
8
(
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(
c) Cox, G. G.; Haigh, D.; Hindley, R. M.; Miller, D. J.; Moody, C. J.
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(
(
Angew. Chem., Int. Ed. 2012, 51, 862. (b) Gulevich, A. V.; Gevorgyan,
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G
dx.doi.org/10.1021/ja408185c | J. Am. Chem. Soc. XXXX, XXX, XXX−XXX

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experimental details.
(23) The structure has been deposited with the Cambridge
Crystallographic Data Centre (CCDC 934423). See the Supporting
Information for details.
(24) A singular example of an O−H insertion with tert-butyl alcohol
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(
6
(
(
7) For recent reviews of donor−acceptor carbenes, see: (a) Davies,
1
(
1.
25) Aggarwal, V. K.; Sheldon, C. G.; Macdonald, G. J.; Martin, W. P.
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(
8) For example, see: Liu, R.; Zhang, M.; Winston-McPherson, G.;
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(
this transformation was reported. However, the product was not
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(
Gevorgyan, V. Angew. Chem., Int. Ed. 2007, 46, 4757. (b) Horneff, T.;
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(
27) Norbert, K.; Hashmi, A. S. K. Modern Allene Chemistry; Wiley:
New York, 2004.
28) The structure has been deposited with the Cambridge
(
Crystallographic Data Centre (CCDC 934422). See the Supporting
Information for details.
(
l) Grimster, N.; Zhang, L.; Fokin, V. V. J. Am. Chem. Soc. 2010, 132,
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Chem. Soc. 2011, 133, 10352. For a discussion of mechanism, see:
b) Doyle, M. P. Catalytic Carbene Complexes in Organic Synthesis:
2
(
(
(
DiazodecompositionInsertion and Ylide Chemistry. In Comprehen-
sive Organometallic Chemistry II; Hegedus, L. S., Ed.; Pergamon Press:
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(
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(
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14) The structure has been deposited with the Cambridge
(
Crystallographic Data Centre (CCDC 934421). See the Supporting
Information for details.
(
15) Simple and weakly basic amines (e.g., aniline) were studied as
substrates in this reaction but in all cases failed to afford the desired
N−H insertion products.
(
16) No reports of vicinal diamine compounds akin to products 5 or
1
(
0 could be found using SciFinder Scholar.
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20) The previously unreported catalyst 1-phenylcyclohexanecarbox-
1
(
ylate (PCC) rhodium(II) dimer was prepared in a manner similar to
that given in ref 18a. See the Supporting Information for experimental
details.
(
2
(
21) Mu
003, 14, 779.
22) The previously unreported catalyst 1-phthalamidocyclohexane-
carboxylate (PTCC) rhodium(II) dimer was prepared in a manner
̈
ller, P.; Allenbach, Y.; Robert, E. Tetrahedron: Asymmetry
H
dx.doi.org/10.1021/ja408185c | J. Am. Chem. Soc. XXXX, XXX, XXX−XXX