Yb(iii)-catalysedsyn-thioallylation of ynamides

Article abstract of DOI:10.1039/d1cc02611a

Reported herein is asyn-thioallylation of ynamides incorporating a sulfide moiety at the α-position and an allyl group at the β-position of the ynamide. The transformation is successful under ytterbium(iii)-catalysis, providing access to highly substituted thioamino-skipped-dienes with broad substrate scope. Thus, tetrasubstituted olefins (with four different functional groups: amide, phenyl, thioaryl/alkyl, and allyl on the carbon centers) are made in a single step from readily accessible ynamides, preserving complete atom economy. The reaction can be extended to the synthesis of selenoamino dienes by ynamidesyn-selenoallylation. DFT studies and control experiments provide insight into the reaction mechanism.

Full text of DOI:10.1039/d1cc02611a

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Yb(III)-catalysed syn-thioallylation of ynamides†
a
a
Manash Protim Gogoi,
Rajeshwer Vanjari, ‡a B. Prabagar,
‡
Cite this: Chem. Commun., 2021,
57, 7521
Shengwen Yang,‡bc Shubham Dutta,a Rajendra K. Mallick,a Vincent Gandon*bc and
a
Akhila K. Sahoo
*
Received 18th May 2021,
Accepted 23rd June 2021
DOI: 10.1039/d1cc02611a
rsc.li/chemcomm
Reported herein is a syn-thioallylation of ynamides incorporating a germylallylation of ynamides is known to provide a-allylated
sulfide moiety at the a-position and an allyl group at the b-position of amino-skipped dienes (Fig. 1b),4 a useful motif amenable to
the ynamide. The transformation is successful under ytterbium(III)- further functionalization for the synthesis of complex organic
catalysis, providing access to highly substituted thioamino-skipped- molecules. Moreover, the gold catalysed carbothiolation of
dienes with broad substrate scope. Thus, tetrasubstituted olefins (with alkynes in this regard is worth mentioning.5 In this context,
four different functional groups: amide, phenyl, thioaryl/alkyl, and allyl an attempt to achieve a-thiolation and b-allylation in a single
on the carbon centers) are made in a single step from readily accessible operation appears appealing, which is a reverse of the known
ynamides, preserving complete atom economy. The reaction can be protocols for b-thiolation and a-allylation; this method also
extended to the synthesis of selenoamino dienes by ynamide syn- generates synthetically important ketene-N,S-acetal5d skipped
selenoallylation. DFT studies and control experiments provide insight dienes. Besides, devising a syn-difunctionalization method
into the reaction mechanism.
surpassing the geometrical constraints linked to the incorpora-
tion of two groups on the same side of an unsaturated system is
Ynamide is a prominent scaffold in organic chemistry that has always stimulating. Lastly, this process could yield tetrasubsti-
been used to develop various innovative transformations, expe- tuted thio-amino-skipped dienes of potential synthetic value by
diently providing novel useful building blocks.1 Among these incorporating the synthetically versatile thio- and allyl groups.
reactions, the 1,2-difunctionalization of ynamides has been We envisioned that an inner sphere addition of a sulfur
particularly studied, leading mostly to substituted enamides.2 nucleophile to the ynamide triple bond under p-Lewis acid
However, the by-products generated in these processes catalysis would yield sulfonium species B through the syn-
decrease their atom efficiency and lack regio- and stereo- nucleometallation of complex A (Fig. 1c). Next, intramolecular
selectivity. Thus, any attempt to develop regio- and stereo- allyl-group migration from the sulfonium-moiety to the vinylic
controlled atom-economic difunctionalizations of ynamides is metal of B by either a [3,3]- or a [1,3]-sigmatropic shift could
undoubtedly worthwhile (Fig. 1a). We describe herein the syn- deliver the syn-thioallylated product as a thio-amino-skipped
thioallylation of ynamides that satisfies these criteria. It stems diene. Herein, we disclose the ytterbium catalyzed syn-
from rare independent examples of thiolation and allylation of thioallylation of N-oxazolidinone derived ynamides and its
ynamides. On the one hand, hydrothiolation of ynamides has extension to syn-selenoallylation. The ynamide a-thiolation
been reported under radical conditions and installs the thio- and b-allylation are distinctive when compared with the known
group at the b-position (Fig. 1b).3 On the other hand, radical approaches (b-thiolation and a-allylation; Fig. 1d) and a unique
way to incorporate an S atom on the ynamide N-side.
To begin with, N-oxazolidinone protected ynamide 1a and
allyl phenyl sulfide 2a were chosen as model substrates and
their reactivities were investigated under Lewis acid catalysis to
a School of Chemistry, University of Hyderabad, Hyderabad, India.
E-mail: akhilchemistry12@gmail.com
b
´
´
Institut de Chimie Moleculaire et des Materiaux d’Orsay, CNRS UMR 8182,
obtain the syn-thioallylation product 3a (see Table S1, ESI†).6
Gratifyingly, among various Lewis acid catalysts and solvents
tested, Yb(OTf)3 (20 mol%) used in 1,2-dichloroethane (DCE) at
80 1C for 8 h was found to be very efficient, yielding 94% of the
desired skipped diene (eqn (1)). Under the optimized condi-
tions, N-sulfonyl protected ynamides (for example 1a0 and 1a00)
were not amenable to undergoing syn-thioallylation and
´
´
ˆ
Universite Paris-Sud, Universite Paris-Saclay, Batiment 420, Orsay cedex 91405,
France
c
´
Laboratoire de Chimie Moleculaire (LCM), CNRS UMR 9168, Ecole Polytechnique,
´
Universite Paris-Saclay, route de Saclay, Palaiseau cedex 91128, France
† Electronic supplementary information (ESI) available. CCDC 2064571. For ESI
and crystallographic data in CIF or other electronic format see DOI: 10.1039/
d1cc02611a
‡ These authors contributed equally.
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Fig. 1 Background and this work.
instead yielded a complex mixture (see Table S2, ESI†).6
Presumably, the coordination of the oxazolidinone carbonyl
moiety to the putative sulfonium-species could help to stabilize
these vinyl–ytterbium intermediates.
Scheme 1 Thioallylation and selenoallylation. aWith inseparable minor
isomer (see ESI†).
good yields; further functionalization of these motifs is therefore
possible. Likewise, syn-thioallylation of 1a with meta-substituted
aryl allyl sulfides 2 [m-OMe (2h), m-OEt (2i), m-Me (2j), m-F (2k),
and m-Cl (2l)] was efficient, yielding 3h (82%), 3i (64%), 3j (80%),
3k (81%), and 3l (78%). The bulky o-substituted aryl sulfides o-Me
(2m), o-F (2n), and o-Br (2o) did not hamper the reaction outcome;
(1)
The scope of this reaction was explored under the optimized the respective skipped amino-dienes 3m–o were accessed. Irre-
spective of the various disubstituents of the aryl sulfides, the
desired skipped dienes 3p (87%), 3q (89%), 3r (97%), and 3s
(82%) were constructed.
Moreover, the reaction was smooth when naphthyl sulfide
(2t) and diallyl sulfide (2u) were independently exposed to 1a,
conditions. The reactivity of allyl sulfides 2a–w with ynamide 1a
was first examined (Scheme 1). To gain insight into the effect of
the aryl-ring substituents on the reaction outcome, various aryl-
allyl-sulfides were exposed to 1a. The reaction of unsubstituted
allyl phenyl sulfide (2a) yielded 94% of product 3a. The reaction
of sulfides [having electron-rich substituents p-tBu (2b), p-iPr yielding 3t and 3u in good yields. The transformation was not
(2c) and p-Me (2d), on the aryl motif] with 1a furnished the only confined to aryl-allyl-sulfides, but alkyl-allyl-sulfides
respective thio-amino-skipped dienes 3b–d in excellent yields. [dodecyl-allyl-sulfide (2v), and methyl-allyl-sulfide (2w)] could
also successfully provide the thioaminal-bearing skipped
dienes 3v (86%) and 3w (90%) (Scheme 1). Notably, the reaction
was also feasible with p-bromoaryl-allyl selenide (5a) to deliver
X-ray crystallographic analysis further confirmed the structure
of 3d (CCDC†: 2064571). Skipped dienes 3e–g bearing labile
and modifiable halo (Cl, Br, and F) groups were accessed in
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the syn-selenyl-allylated skipped dienes 6 albeit in moderate Yb(OTf)2+ to provide the pentavalent species IntA. This process
yield (Scheme 1). However, the selenyl-allylation of ynamide is is highly exergonic by 28.5 kcal molꢀ1. Next, syn-insertion of the
highly substrate-specific and yields an inseparable mixture of alkyne into the S–Yb bond proceeds through transition state
products; current studies are directed to unravelling sustain- tsAB, found at ꢀ13.7 kcal molꢀ1 on the free energy surface, and
able conditions for creating molecular diversity.
gives the vinyl–Yb complex IntB (ꢀ21.6 kcal molꢀ1) with trans-
The scope of differently substituted ynamides was next orientation of the phenyl and sulfide groups. The sulfonium
evaluated (Scheme 1). Ynamides with various aryl substituents cation is stabilized by a non-covalent interaction with one
in the alkyne-terminus [electron-donating: p-OMe (1b) and p-Me oxazolidinone oxygen (nonbonding Oꢁ ꢁ ꢁS distance 3.076 Å,
(1c); electron-withdrawing: p-COMe (1d) and p-CHO (1e); halo see also Fig S3, ESI†).8 Next, a suprafacial [3,3]-sigmatropic
groups: p-Br (1f), p-Cl (1g), p-F (1h)] were reacted with 2d to deliver shift promotes the migration of the allyl-group from the sulfo-
the desired skipped-dienes 4a–g in good yields. Despite the nium to the CQC bond of IntB via the 6-membered ring
presence of carbonyl groups in the substrates, the productivity transition state tsBC, spanning a barrier of 20.7 kcal molꢀ1
was not affected. Likewise, the respective skipped dienes 4h (27.6 kcal molꢀ1 from IntA). This step generates the very stable
(60%), 4i (66%), 4j (59%), 4k (44%), 4l (73%), and 4m (58%) were Yb(III) intermediate IntC, lying at ꢀ36.8 kcal molꢀ1. Of note, it
prepared from ynamides bearing m-aryl substituents in the alkyne was not possible to locate a transition state corresponding to a
terminus with 2d. Once again, the modifiable/transformable [1,3]-sigmatropic shift. Finally, the catalyst is regenerated
functional groups survived and did not affect the reaction. How- with concomitant release of the desired product 3w, which is
ever, alkyl substituted ynamides did not take part in the syn-thio- 16.6 kcal molꢀ1 more stable than the reactants. Thus, the rate-
allylation reaction (probably due to the non-participation of IntC, determining step is allyl migration. By contrast, the corresponding
Fig. 2).
transition state Int-B0 could not be found for the N-sulfonyl
DFT calculations were performed to rationalize the selec- protected ynamides (red lines). Importantly, no sulfonium stabili-
tivity conferred by N-oxazolidinone-protected ynamides.6 The zation was found in this case (Fig. S3, ESI†).6
use of Yb(OTf)3 as an active species led to prohibitively high
´
To further gain some understanding of the mechanistic
energy barriers (see the ESI†).6 Eberlin, Roithova et al. have rationale, various crossover and competitive experiments were
shown that Ln(OTf)3 Lewis acids easily form ion pairs and that performed (Scheme 2). No crossover product was observed when
the corresponding charged metal species are much more active 1a was reacted with a mixture of (2-methylallyl)(phenyl)sulfide
than the neutral one.7 Consistently, the experimental results (20a) and allyl(4-(tert-butyl)phenyl)sulfide (2b); the respective pro-
+
could be rationalized when Yb(OTf)2 was used as the active ducts 30a and 3b were observed through HRMS analysis (eqn (1)).
species (Fig. 2). The transformation begins with the barrierless Thus, allyl group migration is intramolecular. Reaction of the
coordination of ynamide 1a and allyl-methylsulfide (2w) to terminally disubstituted allyl sulfide 3x with 1a yielded the
Fig. 2 DFT analysis: comparison of N-oxazolidinone and N-sulfonyl ynamides (free energy profile, DG353.15 (kcal molꢀ1); selected distances in Å).
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with the addition of two functional groups, sulfide and allyl, on the
ynamide with syn-stereoselectivity. The transformation tolerates
common functional groups and has a broad scope, constructing
a wide range of ketene-N, S-acetal-containing skipped dienes. The
protocol is also amenable to seleno-allylation of the ynamide,
which is also unprecedented. The dual coordination of the catalyst
to the nucleophile and the ynamide and the presence of a
coordinating and relatively small group seem essential for the
syn-thioallylation of ynamides. DFT studies established the involve-
ment of an intramolecular allyl group migration through a [3,3]-
shift rather than a [1,3]-shift. The synthetic utility of thio-amino
skipped dienes was also examined. These findings pave the way for
more expedient thiolative difunctionalizations of ynamides, which
remain underexplored.
The research was supported by SERB-India (grant no.:
CRG-2019-1802). The authors thank the University of Hyder-
abad (UoH-IOE; UPE-CAS, and PURSE-FIST) for the facility.
R. V. thanks SERB-NPDF, and M. P. G., R. K. M., and B. P., S.
D. thank UGC and CSIR India, respectively, for fellowships.
V. G. and S. Y. thank CSC, CNRS, UPSaclay, and Ecole Poly-
technique for financial support.
Conflicts of interest
The authors declare no conflict of interest.
Notes and references
Scheme 2 Mechanistic studies and applications. aWith inseparable minor
isomer (see ESI†).
1 (a) K. A. De Korver, H. Li, A. G. Lohse, R. Hayashi, Z. Lu, Y. Zhang and
R. P. Hsung, Chem. Rev., 2010, 110, 5064; (b) G. Evano, A. Coste and
K. Jouvin, Angew. Chem., Int. Ed., 2010, 49, 2840 (Angew. Chem. Int. Ed.
2010, 122, 2902); (c) X. N. Wang, H. S. Yeom, L. C. Fang, S. He,
Z. X. Ma, B. L. Kedrowski and R. P. Hsung, Acc. Chem. Res., 2014,
47, 560; (d) B. Prabagar, N. Ghosh and A. K. Sahoo, Synlett, 2017,
2539; (e) G. Evano, C. Theunissen and M. Lecomte, Aldrichimica Acta,
2015, 48, 59; ( f ) F. Pan, C. Shu and L.-W. Ye, Org. Biomol. Chem.,
2016, 14, 9456; (g) Y.-B. Chen, P.-C. Qianb and L.-W. Ye, Chem. Soc.
Rev., 2020, 49, 8897.
2 (a) B. Gourdet and H. W. Lam, J. Am. Chem. Soc., 2009, 131, 3802;
(b) M. Takimoto, S. S. Gholap and Z. Hou, Chem. – Eur. J., 2015,
21, 15218; (c) S. Dutta, S. Yang, R. Vanjari, R. K. Mallick, V. Gandon
and A. K. Sahoo, Angew. Chem., Int. Ed., 2020, 59, 10785;
(d) R. K. Mallick, B. Prabagar and A. K. Sahoo, J. Org. Chem., 2017,
82, 10583; (e) J. Yu, G. Xu, S. Tang, Y. Shao and J. Sun, Org. Lett., 2019,
21, 9076; ( f ) R. Vanjari, S. Dutta, M. P. Gogoi, V. Gandon and
A. K. Sahoo, Org. Lett., 2018, 20, 8077; (g) A.-H. Zhou, Q. He,
C. Shu, Y.-F. Yu, S. Liu, T. Zhao, W. Zhang, X. Lu and L.-W. Ye,
Chem. Sci., 2015, 6, 1265.
hydrothiolation product 7 instead of the syn-thioallylated product;
this shows that steric crowding at the terminal carbon hinders the
shift of the allyl group (eqn (2)). To further validate the mode of
allyl-shift shown in Fig. 2, the reaction of 1a with allyl(benzyl)
sulfide (3y) under the optimized conditions was carried out.
Formation of product 8 (78%) indicates that the allyl group
migration is facile over the benzyl group (eqn (3)) and no shift
of the benzyl group through a [1,3]-shift was observed. Moreover,
the reaction of phenyl(benzyl) sulfide (3z) with 1a resulted in
hydrothiolation rather than the thio-benzylation product, which is
indicative of the non-involvement of a [1,3]-shift (eqn (4)). To
further validate the [3,3]-shift of the allyl group, attempts to
synthesize allyl sulfides exclusively deuterated at the terminal
carbon were unsuccessful.
3 (a) B. Banerjee, D. N. Litvinov, J. Kang, J. D. Bettale and S. L. Castle,
Org. Lett., 2010, 12, 2650; (b) A. Sato, H. Yorimitsu and K. Oshima,
Synlett, 2009, 28.
The synthetic potential of the skipped dienes was next investi- 4 K. D. L. V. Hernandez, E. Romain, A. Coffinet, K. Bijouard,
G. Gontard, F. Chemla, F. Ferreira, O. Jackowski and A. P. Luna,
J. Am. Chem. Soc., 2018, 140, 17632.
5 (a) H. Kim, J. Jang and S. Shin, J. Am. Chem. Soc., 2020, 142, 20788;
(b) J. Wang, S. Zhang, C. Xu, L. Wojtas, N. G. Akhmedov, H. Chen and
X. Shi, Angew. Chem., Int. Ed., 2018, 57, 6915; (c) I. Nakamura, T. Sato
and Y. Yamamoto, Angew. Chem., Int. Ed., 2006, 45, 4473; (d) L. Zhang,
J. Dong, X. Xu and Q. Liu, Chem. Rev., 2016, 116, 287.
gated, starting with the gram scale preparation of 3a with 10 mol%
catalyst loading (eqn (5), Scheme 2). Interestingly, the double bond
migration of 2-methylallyl sulfide (20a) occurred during the reaction
with 1a, leading to the conjugated-dienamides 30a in 84% yield
(eqn (6), Scheme 2). The Pd-catalyzed Heck coupling of 3a terminal
olefin with p-methoxy aryl diazonium salt (9) yielded 62% of the 6 See the ESI†.
7 G. L. Tripodi, T. C. Correra, C. F. F. Angolini, B. R. V. Ferreira,
p-conjugated amino-diene 10 (eqn (7), Scheme 2).
ˆ
´
P. Maıtre, M. N. Eberlin and J. Roithova, Eur. J. Org. Chem., 2019,
In summary, a 1,2-syn-thioallylation of ynamides has been
3560.
developed for the first time. The transformation is atom-efficient 8 R. Taylor, J. Chem. Inf. Model., 2011, 51, 897.
7524 | Chem. Commun., 2021, 57, 7521–7524
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