One-pot synthesis of oxazolidinones and five-membered cyclic carbonates from epoxides and chlorosulfonyl isocyanate: Theoretical evidence for an asynchronous concerted pathway

Article abstract of DOI:10.3762/BJOC.16.148

The one-pot reaction of chlorosulfonyl isocyanate (CSI) with epoxides having phenyl, benzyl and fused cyclic alkyl groups in different solvents under mild reaction conditions without additives and catalysts was studied. Oxazolidinones and five-membered cyclic carbonates were obtained in ratios close to 1:1 in the cyclization reactions. The best yields of these compounds were obtained in dichloromethane (DCM). Together with 16 known compounds, two novel oxazolidinone derivatives and two novel cyclic carbonates were synthesized with an efficient and straightforward method. Compared to the existing methods, the synthetic approach presented here provides the following distinct advantageous: being a one-pot reaction with metal-free reagent, having shorter reaction times, good yields and a very simple purification method. Moreover, using the density functional theory (DFT) method at the M06-2X/6-31+G(d,p) level of theory the mechanism of the cycloaddition reactions has been elucidated. The further investigation of the potential energy surfaces associated with two possible channels leading to oxazolidinones and five-membered cyclic carbonates disclosed that the cycloaddition reaction proceeds via an asynchronous concerted mechanism in gas phase and in DCM.

Full text of DOI:10.3762/BJOC.16.148

One-pot synthesis of oxazolidinones and five-membered
cyclic carbonates from epoxides and chlorosulfonyl
isocyanate: theoretical evidence for an
asynchronous concerted pathway
Esra Demir1, Ozlem Sari2, Yasin Çetinkaya3, Ufuk Atmaca1,3, Safiye Sağ Erdem4
and Murat Çelik*1
Full Research Paper
Open Access
Address:
Beilstein J. Org. Chem. 2020, 16, 1805–1819.
1Department of Chemistry, Faculty of Science, Atatürk University,
25240 Erzurum, Turkey, 2Department of Chemistry, Faculty of Arts
and Sciences, Kırşehir Ahi Evran University, 40100 Kırşehir, Turkey,
3Department of Food Technology, Oltu Vocational School, Atatürk
University, 25400 Oltu, Erzurum, Turkey and 4Department of
Chemistry, Faculty of Arts and Sciences, Marmara University,
Goztepe Campus, 34722 Istanbul, Turkey
doi:10.3762/bjoc.16.148
Received: 09 April 2020
Accepted: 02 July 2020
Published: 21 July 2020
Associate Editor: P. Schreiner
Email:
© 2020 Demir et al.; licensee Beilstein-Institut.
License and terms: see end of document.
Murat Çelik* - mcelik@atauni.edu.tr
* Corresponding author
Keywords:
chlorosulfonyl isocyanate; computational modeling; cyclic carbonates;
density functional theory; oxazolidinone
Abstract
The one-pot reaction of chlorosulfonyl isocyanate (CSI) with epoxides having phenyl, benzyl and fused cyclic alkyl groups in dif-
ferent solvents under mild reaction conditions without additives and catalysts was studied. Oxazolidinones and five-membered
cyclic carbonates were obtained in ratios close to 1:1 in the cyclization reactions. The best yields of these compounds were ob-
tained in dichloromethane (DCM). Together with 16 known compounds, two novel oxazolidinone derivatives and two novel cyclic
carbonates were synthesized with an efficient and straightforward method. Compared to the existing methods, the synthetic ap-
proach presented here provides the following distinct advantageous: being a one-pot reaction with metal-free reagent, having
shorter reaction times, good yields and a very simple purification method. Moreover, using the density functional theory (DFT)
method at the M06-2X/6-31+G(d,p) level of theory the mechanism of the cycloaddition reactions has been elucidated. The further
investigation of the potential energy surfaces associated with two possible channels leading to oxazolidinones and five-membered
cyclic carbonates disclosed that the cycloaddition reaction proceeds via an asynchronous concerted mechanism in gas phase and in
DCM.
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Introduction
Oxazolidinones (1), five-membered heterocyclic rings contain- carbonyl-α-ᴅ-glucopyranoside (MBCG) (5) [19,20] and glycer-
ing an ester group adjacent to a nitrogen atom, are important ol carbonate (6) [21] were also reported (Scheme 1).
compounds in synthetic and pharmaceutical chemistry because
of their considerable use as antibiotics [1], immunomodulators Therefore, numerous synthetic approaches have been de-
[2], antibacterials [3], as well as synthetic intermediates and veloped to date for the preparation of oxazolidinones and five-
chiral auxiliaries for various organic conversions [4-7]. Line- membered cyclic carbonates of various structures. The most
zolid [1-3] (3) and cytoxazone [8,9] (4) are oxazolidinone deriv- well-known strategies for the synthesis of oxazolidinones are
atives having significant biological activities. Linezolid (3) is the reaction of an amino alcohol with phosgene [5,22], the
the first oxazolidinone drug approved in 2000 by the Food and carbonylation reaction of β-amino alcohols with CO2 or dialkyl
Drug Administration (FDA) for the treatment of multidrug carbonates [23-27], the multicomponent reaction of rare-earth
resistant Gram-positive bacterial infections (Scheme 1) [10]. metal amides [28], the reaction of CO2 with propargylamines or
Cytoxazone is a microbial metabolite exhibiting potent aziridines [29,30] and the cycloaddition reaction of epoxides
cytokine-modulating activity. Tedizolid phosphate (trade name with isocyanates [31,32]. On the other hand, for the synthesis of
Sivextro), which exhibits antibiotic activity is another oxazo- five-membered cyclic carbonates, the cycloaddition of CO2 to
lidinone drug approved by the FDA in 2014 [11]. Befloxatone epoxides, the reaction with the metal complexes or catalysts,
and toloxatone, N-substituted phenyloxazolidinone derivatives, and the reaction of a diol with toxic phosgene are the most
are reversible inhibitors of monoamine oxidase (MAO) [12,13]. common processes [16,17,33-36].
N-Aryloxazolidinedione compounds, which are toloxatone de-
rivatives, have been reported to exhibit good affinity for human CSI, a highly reactive and versatile isocyanate, reacts with
MAO-A [14].
epoxides to give five-membered cyclic carbonates and oxazo-
lidinones [37-39]. In 1984, Keshava Murthy and Dhar reported
Five-membered cyclic carbonate (1,3-dioxolan-2-one) (2) and the synthesis of five-membered cyclic carbonates and oxazolidi-
its derivatives are valuable synthetic targets on account of nones from various epoxides in two steps using CSI and KOH
several applications and pertinent properties. They are found in in benzene/dichloromethane [40,41]. In 1986, De Meijere and
various natural and potential pharmaceutical products [15]. co-workers reported the cycloaddition of CSI to epoxides at
Moreover, they are used as electrolyte components in Li-ion −78 °C to give five-membered cyclic carbonates and oxazolidi-
rechargeable cells and as aprotic polar solvent with high boiling nones [42]. They reported seven examples; three of these
point as alternative of dangerous solvents because of their good attempts resulted in five-membered cyclic carbonates as the sole
biodegradability and low toxicity [16-18]. Synthetic intermedi- product while two cases produced oxazolidinones, and the other
ates for ring-opening polymerization of the compounds contain- two reactions gave mixtures of two products. These reports
ing cyclic carbonates such as methyl 4,6-O-benzylidene-2,3-O- prompted us to explore this reaction in more detail. In our
Scheme 1: Oxazolidinone (1), five-membered cyclic carbonate (2) and some important compounds containing an oxazolidinone ring (3, 4) or a five-
membered cyclic carbonate (5, 6).
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previous studies, we investigated the reactions of CSI with Results and Discussion
various substrates such as carboxylic acids, alkenes and allyl or First, we synthesized various epoxides (7a–j) in the presence of
benzyl alcohols [43-46]. As a continuation of these studies, we meta-chloroperbenzoic acid (m-CPBA), from the correspond-
performed one-pot syntheses of the title compounds by optimiz- ing alkenes dissolved in DCM at room temperature. The general
ing the reaction of CSI with epoxides in different solvents under experimental conditions for conversion of alkenes to related
mild conditions and compared the reaction mechanism with pre- epoxides were given in Supporting Information File 1. For the
viously proposed mechanisms using theoretical calculations.
synthesis of oxazolidinones and five-membered cyclic carbon-
ates, the most effective solvent was determined based on the
Keshava Murthy and Dhar [41] postulated a mechanism involv- reaction of 8-oxabicyclo[5.1.0]octane (7b) with CSI (Table 1)
ing a zwitterionic intermediate. C–O bond cleavage in this which was the first reaction performed in this study. The reac-
unstable and strained intermediate gives rise to a short-lived tion was carried out in acetone, THF, acetonitrile, dichloro-
carbonium ion which will be attacked by the nucleophilic part methane, toluene, and n-hexane/dichloromethane. While no
of the zwitterion in a concerted way (Scheme 2a). De Meijere reaction was observed in diethyl ether, the best conversion was
and co-workers [42] proposed a mechanism involving a 1,5- achieved in dichloromethane. Benzene was not used as a sol-
dipolar intermediate (Scheme 2b).
vent because of having toxic and carcinogenic effects.
To the best of our knowledge, there is no computational mecha- Herein, we report mild reaction conditions for the one-pot syn-
nistic study in the literature regarding the reaction of epoxides thesis of oxazolidinones and five-membered cyclic carbonates
with CSI. On the other hand, the reactions of isocyanates with from various epoxides (7a–j) at room temperature without using
monofluoroalkenes and nitrones were modeled with the any catalyst.
Møller–Plesset (MP2) perturbation theory and M06-2X func-
tional, respectively [37,47]. According to these computational After having identified the optimal conditions, various epox-
studies, such reactions of isocyanates may proceed through a ides were treated with chlorosulfonyl isocyanate at room tem-
concerted pathway. The remaining uncertainties in the mecha- perature to give mixtures of cyclic carbonates and oxazolidi-
nisms of the similar reactions inspired us to carry out quantum nones in ratios close to 1:1 as shown in Table 2. trans-Stilbene
chemical calculations for the formation of oxazolidinone and (7d) and cis-stilbene epoxids (7e) in the presence of CSI gave
five-membered cyclic carbonates.
trans-4,5-diphenyl-1,3-dioxolan-2-one (8d), trans-4,5-diphenyl-
Scheme 2: Proposed mechanisms by Keshava Murthy and Dhar [41] and De Meijere and co-workers [42].
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Table 1: Solvent optimization for the synthesis of five-membered cyclic carbonate 8b and oxazolidinone 9b from epoxide 7b.
Entry
Solvents
Products (%)a
Five-membered cyclic
carbonate 8b
Oxazolidinone 9b
1
2
3
4
5
6
7
acetone
11
15
12
THF
15
diethyl ether
no reaction
CH3CN
39
48
13
21
34
45
15
19
dichloromethane
toluene
n-hexane/dichloromethane (1:1)
aIsolated yield.
Table 2: Direct conversion of epoxides 7a–j with CSI into five-membered cyclic carbonates 8a–j and oxazolidinones 9a–j.
Entry
Substratesa
Productsb (%)
Five-membered cyclic
carbonatesc
Oxazolidinonesc
1
2
3
42%
8a [48]
38%
9a [49]
7a
7b
7c
48%
8b [50]
45%
9b [51]
51%
8c [50]
40%
9c
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Table 2: Direct conversion of epoxides 7a–j with CSI into five-membered cyclic carbonates 8a–j and oxazolidinones 9a–j. (continued)
4
7d
43%
8d [50]
34%
9d [52]
5
7e
44%
8e [50]
41%
9e [52]
6
7f
49%
8f [16]
42%
9f [16]
7
7g
41%
8g [16]
35%
9g [53]
8
9
7h
45%
8h [54]
40%
9h [52]
43%
8i
37%
9i
7i
10
44%
8j
42%
9j [55]
7j
aSynthesis of epoxides 7a–j: alkenes (1 equiv), m-CPBA (1.2 equiv), in DCM; bisolated yield; cliterature.
oxazolidin-2-one (9d) and cis-4,5-diphenyl-1,3-dioxolan-2-one preserved. 4-Phenyl-1,3-dioxolan-2-one (8f) and 4-phenyloxa-
(8e), cis-4,5-diphenyloxazolidin-2-one (9e), respectively zolidin-2-one (9f) were obtained from the reaction of CSI with
(Table 2). These results show that the relative configuration is styrene oxide (7f) showing the regioselective nature of the reac-
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tion. In addition, we report the synthesis of the novel oxazolidi- tions using a simple purification method. Apparently, our
none derivatives 8i, and 8j and 1,3-dioxolan-2-ones 9c and 9i. protocol describes a reasonable methodology for the conver-
Furthermore, a more efficient and straightforward method for sion of epoxides to protected 1,2-diols and 2-amino alcohols.
the formation of the previously known 8a–h, 9a–b, 9d–h and 9j Attention is drawn on these 1,2-oxygen and/or nitrogen units
is being described.
since they are present in natural products ranging from small
molecules, such as sugars, lipids and amino acids to huge mole-
In the study of Keshava Murthy and Dhar, five-membered cules [56].
cyclic carbonates and oxazolidinones from epoxides were syn-
thesized in two stages using CSI and KOH in dry benzene/ Computational results
dichloromethane (5:1) at −10 °C [40,41]. They reported five- A detailed mechanistic investigation of the synthesis of oxazo-
membered cyclic carbonates as the main products in the lidinone and five-membered cyclic carbonate derivatives by the
reaction mixture in good yields (83.9–95.9%, totally), but with reaction between epoxide 7f and CSI has been performed.
only five examples. It is also known today that benzene is
carcinogenic, and not preferred as a solvent unless it is neces- Formation of oxazolidinone 9f
sary. This two-step methodology required several purification There are two possible channels for the cyclization reaction of
methods. However, our purification process is remarkably epoxide 7f with CSI to form oxazolidinone intermediates 10
simple and shorter. Moreover, using ten examples (Table 2), and 11 as shown in Figure 1. In both transition states it is found
twenty distinct products were synthesized in good yields that the ring-opening reaction of the epoxide, a nucleophilic
(76–93%, totally).
attack of N4 onto C1 or C2 and an attack of O3 on C5 occur in
an asynchronous concerted manner. The first transition state
On the other hand, in the study of De Meijere and co-workers, (TS1) corresponds to the nucleophilic attack of N4 onto the C2
the reaction started at −78 °C to give five-membered cyclic of 7f leading to oxazolidinone intermediate 10. The alternative
carbonates and oxazolidinones using seven examples [42]. transition state (TS1′) corresponds to the nucleophilic attack of
Three of these attempts resulted in five-membered cyclic N4 onto the less sterically encumbered C1 atom of the epoxide
carbonates as the sole products while in two cases oxazolidi- 7f forming intermediate 11. Optimized geometries of transition
nones were produced, and the other two reactions gave mix- structures are depicted in Figure 1.
tures of two products. The purification process of this method
also required several steps resulting in relatively lower yields Our calculated results for the reaction indicate 17.4 kcal/mol
(20–67% yields, totally). Compared to this study, our study pro- (gas phase) and 26.7 kcal/mol (in DCM) preference for the TS1
vided higher yields in shorter reaction times under mild condi- over the TS1′ (Figure 2). Therefore, attack by N4 of CSI on the
Figure 1: Possible pathways for the formation of oxazolidinone intermediates 10 and 11. Optimized transition structures at PCM/M06-2X/6-
31+G(d,p)//M06-2X/6-31+G(d,p) level in DCM. Distances are given in Å.
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C2 of epoxide is found to be energetically the most favored ap-
proach.
The epoxide ring opening and formation of the O–C(=O) bond
are almost completed before the C–N bond is formed. The
changes in bond lengths along the intrinsic reaction coordinate
(IRC) are depicted in Figure 3a and b as an acceptable ap-
proach in the literature [57]. For the formation of 10, the
O–C(=O) distance is shortened and C2–O3 bond is elongated
rapidly until reaching the product, while the C2–N4 distance is
shortened from 2.76 Å in TS1 to 2.59 Å in I-41 (Figure 3a).
Note that I-41 is not yet the product but the 41st point in the
IRC where the C2–N4 distance will eventually decrease to the
bond distance when the number of IRC points are increased.
These results refer to asynchronous events. The same trend is
observed for the formation of 11 as shown in Figure 3b. Note-
worthy, the C2–N4 bond length does not change much along
the IRC for the formation of 10; however, it is shortened more
rapidly to give 11. The presence of partial double bond be-
Figure 2: Potential energy profile related to the formation of oxazolidi-
none intermediates 10 and 11 at the PCM/M06-2X/6-31+G(d,p)//M06-
2X/6-31+G(d,p) level in DCM. Gas phase energies are shown in
parenthesis. (The polarization effect of the solvent was considered
implicitly.)
Figure 3: IRC calculated for the formation of (a) 10 and (b) 11 at M06-2X/6-31+G(d,p) level. I-1, I-15, I-35, I-41, etc. are the selected points along the
coordinate. Distances are given in Å.
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tween C2–C(Ph) (benzylic position) allows electron delocaliza- Figure 4. This step is common for all paths studied which will
tion around the reacting center, which results in stabilization of be described below.
the transition state and so lowering the activation energy barrier
(Figure 3a). On the other hand, stabilization of the benzylic Once 10 is formed, the next step is addition of water. This step
cation is not possible along the IRC path for TS1′ (Figure 3b), can occur along three different pathways namely path 1a, path
since the bond distance C2–C(Ph) is found as around 1.50 Å 1b and path 2 as shown in Scheme 3. The potential energy
showing a single bond character. This can be the main reason profile of each path was generated relative to the energy of the
for the predominant formation of intermediate 10 which results initial reactant complex RC1 (7f+CSI) (Figure 5). Paths 1a and
in the regioselective formation of oxazolidinone 9f
1b represent the protonation of the ring nitrogen by one and two
water molecules, respectively, and the departure of 12. In path
Optimized geometries for reactant complex RC1 (7f+CSI), 1a, the transformation of the TS2 to 9f involves the shortening
transition state TS1 and 10 for the selected path are depicted in of the N4–H8 distance from 1.46 to 1.01 Å and S6–O7 distance
Figure 4: Optimized geometries for the stationary points for the formation of 10 at PCM(DCM)/M06-2X/6-31+G(d,p)//M06-2X/6-31+G(d,p) level
(common step of path 1a, path 1b and path 2). Distances are given in Å.
Scheme 3: Proposed mechanisms for the formation of oxazolidinone 9f.
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Figure 5: Potential energy profiles for paths 1a (blue), 1b (red), 2 (green) and relative Gibbs free energies (kcal/mol) in DCM related to the formation
of 9f at PCM(DCM)/M06-2X/6-31+G(d,p)//M06-2X/6-31+G(d,p) level.
from 1.89 to 1.54 Å (Supporting Information File 1, Figure S1). Alternatively, the mechanism may involve path 2 where the ad-
This path occurs via the four-membered ring transition state dition of water molecules to the chlorosulfonyl moiety and the
TS2 with an energy barrier of 23.5 kcal/mol relative to RC1 departure of H2SO4 are observed (Scheme 3). The first step of
(7f+CSI).
path 2 involves addition of two water molecules to RC4
(10+2H2O) resulting in elimination of hydrated HCl and
Another scenario (path 1b) is the direct participation of two formation of 13. The calculated free energy of activation was
water molecules in six-membered TS3 leading to the target found to be 15.4 kcal/mol with respect to RC1
product 9f. As can be seen from Figure 6, the distance of (7f+CSI) (Figure 5). The final step of path 2 takes place from
N4–H8 is calculated as 1.41 Å in TS3, which is further short- RC5 (13+H2O) passing through TS5 and forming the target
ened to 1.06 Å in PC3 (9f+12+H2O). Obviously, the proton product 9f. This step requires an activation free energy of
shuttle activation mechanism pathway is energetically more 16.2 kcal/mol with respect to the initial reactant complex RC1
favorable, which involves a lower barrier of 8.4 kcal/mol with (7f+CSI) (Figure 5). The overall process is exothermic by
respect to RC1 (7f+CSI) (Figure 5).
56.2 kcal/mol. Three-dimensional (3D) views of all the opti-
Figure 6: Optimized geometries for the stationary points of path 1b at PCM(DCM)/M06-2X/6-31+G(d,p)//M06-2X/6-31+G(d,p) level. Distances are
given in Å.
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Beilstein J. Org. Chem. 2020, 16, 1805–1819.
mized structures of path 2 are illustrated in Supporting Informa-
tion File 1, Figure S2.
As can be seen from the potential energy profile (Figure 5),
water addition to 10 is likely to be the rate-determining step for
all reaction pathways. Comparison of the calculated Gibbs free
energies of activation in DCM reveals that path 1b is the most
plausible mechanism among the paths studied.
The reaction mechanism for the formation of five-membered
cyclic carbonate 8f has also been investigated theoretically and
it is described below (Scheme 4).
Figure 7: Potential energy profile and relative Gibbs free energies
(kcal/mol) in DCM related to the formation of 8f at PCM(DCM)/M06-2X/
6-31+G(d,p)//M06-2X/6-31+G(d,p) level.
A similar transition state has been proposed for the formation
of 8f in the presence of CSI. The mechanism is thought to
proceed by ring opening of the epoxide 7f at the 2-position, fol-
lowed by nucleophilic attack of O4 on C2 to afford 16. The for- structures are given in Figure 10. The elimination reaction, via
mation of 16 is exergonic by 30.4 kcal/ mol relative to RC6 the transition state TS8, is facile and leads to the stable product,
(7f+CSI) (Figure 7). The optimized geometries are illustrated in the five-membered cyclic carbonate 8f (Figure 7).
Figure 8.
In the experimental studies for the reaction of epoxides with
The intermediate RC7 (16+H2O), generated by the reaction of CSI, Keshava Murthy and Dhar [41] suggested a stepwise reac-
CSI with epoxide 7f, reacts with a water molecule to yield 17. tion passing through a zwitterionic intermediate (Scheme 2a).
The bond distance C5–N6 is predicted as 1.29, 1.41, and 1.46 Å De Meijere and co-workers [42] proposed a two-step process
in structures RC7 (16+H2O), TS7, and 17, respectively involving a 1,5-dipolar intermediate (Scheme 2b). However, in
(Figure 9). Besides, the C5−O7 distance is 1.58 Å in TS7; it is this work, we introduce a new mechanism by providing compu-
shortened to 1.39 Å in 17. Here, while the O7–H8 single bond tational evidence for the asynchronous concerted pathway for
is broken, the N6−H8 bond is formed. The corresponding the first addition step of epoxides to CSI. Previous computa-
barrier was calculated to be 13.0 kcal/mol relative to initial tional studies [37,47] involve reactions of CSI with substrates
reactant complex RC6 (7f+CSI) (Figure 7).
other than epoxides and therefore they are not directly compa-
rable to our reaction; however, they proposed that the reactions
Elimination of 18, accompanied by C=O bond formation, of isocyanates may take place through a concerted mechanism.
constitutes the final step of the reaction observed. Optimized These results are consistent with our computational findings.
Scheme 4: Proposed mechanism for the formation of five-membered cyclic carbonate 8f.
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Figure 8: Optimized geometries for the stationary points of step 1 for the formation of 16 at PCM(DCM)/M06-2X/6-31+G(d,p)//M06-2X/6-31+G(d,p)
level. Distances are given in Å.
Figure 9: Optimized geometries for the stationary points of step 2 for the formation of 17 at PCM(DCM)/M06-2X/6-31+G(d,p)//M06-2X/6-31+G(d,p)
level. Distances are given in Å.
Figure 10: Optimized geometries for the stationary points of step 3 for the formation of PC8 at PCM(DCM)/M06-2X/6-31+G(d,p)//M06-2X/6-31+G(d,p)
level. Distances are given in Å.
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Conclusion
all stationary points to verify whether they are minima (no
In summary, in the first part of the study, we have improved the imaginary frequencies) or transition states (a single imaginary
general synthesis of five-membered cyclic carbonates and frequency). Thermodynamic calculations have been performed
oxazolidinones from various epoxides under mild conditions. at 25 °C and 1 atm. The same level of intrinsic reaction coordi-
We also described the synthesis of novel oxazolidinone deriva- nate (IRC) [62,63] calculations have been performed to check
tives 8i and 8j and 1,3-dioxolan-2-ones 9c and 9i. Moreover, an the energy profiles connecting each transition state to the two
effective and simplistic procedure for the synthesis of known associated minima. The effect of the solvent environment on the
compounds 8a–h, 9a,b, 9d–h and 9j has been reported. Com- reaction pathways has been taken into account by single-point
pared to the existing methods in the literature, this versatile energy calculations on the gas-phase stationary points using a
conversion has enabled us to create a wide range of cyclic polarizable continuum model (PCM) [64] at M06-2X/6-
carbonates and oxazolidinones in ratios close to 1:1 using a 31+G(d,p) level. Structural representations were generated
safe, inexpensive, metal-free reagent, a simple purification using CYLView [65].
method and shorter reaction times via a one-pot reaction. The
Experimental
epoxides to protected 1,2-diols and 2-amino alcohols in one General considerations
study presents a useful method for one-pot conversion of
reaction.
The epoxides were synthesized from related alkenes with
m-CPBA and purified in a filter column. All solvents and
In the computational part of the study, the mechanisms leading reagents were used as purchased from commercial suppliers
to oxazolidinone 9f and cyclic carbonate 8f were examined. The without any purification. Melting points were determined on a
calculated energy difference between the TS1 (leading to 9f) melting-point apparatus (Gallenkamp; WA11373) and are
and TS6 (leading to 8f) is very small (0.5 kcal/mol) but slightly uncorrected. IR spectra were obtained from solutions in 0.1 mm
in favor of carbonate 8f which is in very good agreement with cells and in CH2Cl2 with a Perkin–Elmer spectrophotometer. 1H
the experimental observation that isolated yields are 49% for 8f and 13C NMR spectra were recorded on Varian and Bruker
and 42% for 9f. The potential energy profiles of the formation spectrometers at 400 and 100 MHz, respectively, and NMR
of 8f and 9f are quite similar. IRC calculations revealed that the shifts are presented as δ in ppm. Elemental analyses were per-
first step of the mechanisms for the formation of 8f and 9f occur formed on a LECO CHNS-932 apparatus. MS spectra were
asynchronously although in a concerted fashion. The water ad- carried out on an LC–MS high-resolution time of flight (TOF)
dition steps are likely to be rate-determining for both reaction Agilent 1200/6530 instrument. All column chromatography was
mechanisms. Besides, explicit inclusion of water molecules is performed on silica gel (60-mesh, Merck).
crucial for lowering the energy barrier making the process plau-
General procedure for the synthesis of five-
sible without changing the nature of the rate determining step of
membered cyclic carbonates and
oxazolidinones
the formation of 9f.
Our computational results adequately explain the relative yields Epoxide 7a (500 mg, 4.54 mmol, 1 equiv) was dissolved in
and confirm the product ratio detected in the experiment as well 20 mL dichloromethane. The reaction mixture was cooled to
as the regioselectivity in oxazolidinones The proposed mecha- 0 °C, and chlorosulfonyl isocyanate (CSI, 707 mg, 4.99 mmol,
nisms in this study confirm the product ratio detected in the ex- 1.1 equiv) was added. The resulting solution was stirred at room
periment. The computational findings provided insight into the temperature for 1 h. Then, water was added to the reaction mix-
formation of experimentally observed oxazolidinone 9f since its ture (2 mL), and the mixture was stirred for 0.5 h. The reaction
precursor intermediate 10 has a remarkably lower activation mixture was extracted with dichloromethane (3 × 20 mL). The
barrier compared to 11.
organic phase was dried over sodium sulfate and concentrated.
Purification was performed through column chromatography on
silica gel eluting with hexane/EtOAc (4:1). In all reactions, 1,3-
Methodology
All calculations have been carried with the Gaussian 09 dioxolan-2-ones (8a–j) were isolated as the first fraction and
program package [58]. Geometry optimizations of all the oxazolidinones, (9a–j) as the second fraction.
minima and transition states involved have been performed
using M06-2X [59,60] /6-31+G(d,p) level of theory. The Octahydrocycloocta[d]oxazol-2(3H)-one (9c): Colourless
M06-2X functional is known to show good performance in solid, Rf = 0.4 (EtOAc/hexanes, 1:5); mp 91–93 °C; (268 mg,
predicting the activation energies and transition state geome- yield 40%); 1H NMR (400 MHz, CDCl3, ppm) δ 4.70–4.65 (m,
tries of various reactions [59-61]. Harmonic vibrational 1H, CH-O), 4.57–4.53 (m, 1H, CH-N), 2.28–0.95 (m, 12H,
frequencies have been calculated at the same level of theory for 6×CH2); 13C NMR (100 MHz, CDCl3, ppm) δ 148.9 (C=O),
1816

Beilstein J. Org. Chem. 2020, 16, 1805–1819.
80.7 (C-O), 65.7 (C-N), 26.9 (CH2), 25.3 (CH2), 28.4 (CH2), Funding
25.3 (CH2), 24.9 (CH2), 24.2 (CH2); IR (CHCl3, cm−1): 3251, We are grateful to the Scientific Research Project of the Atatürk
2928, 2863, 1805, 1410, 1358, 1210, 1175, 1034; anal. calcd University of Turkey (BAP) for a grant [2016/158].
for: C, 63.88; H, 8.93; N, 8.28; found: 63.56; H, 9.04; N, 8.54;
HRMS–ESI (m/z): [M + H]+ calcd for C9H15NO2+, 169,1097;
ORCID® iDs
Ufuk Atmaca - https://orcid.org/0000-0002-5598-0443
found, 169,1086.
Murat Çelik - https://orcid.org/0000-0003-3485-7822
3a,4,9,9a-Tetrahydro-4,9-methanonaphtho[2,3-
d][1,3]dioxol-2-one (8i): Colourless solid, Rf = 0.5 (EtOAc/
hexanes, 1:5); mp 102–104 °C. (287 mg, yield 43%); 1H NMR
(400 MHz, CDCl3, ppm) δ 7.27–7.18 (m, 4H, ArH), 4.62 (s,
2H, CH-O), 3.62 (s, 2H, CH), 2.16 (s, 2H, CH2); 13C NMR
(100 MHz, CDCl3, ppm) δ 154.0 (C=O), 142.2 (Ar), 128.1 (Ar),
123.3 (Ar), 80.5 (C-O), 47.9 (CH), 41.6 (CH2); IR (CHCl3,
cm−1): 2932, 1804, 1460, 1160, 1066, 976; anal. calcd for: C,
71.28; H, 4.98; found: C, 71.43; H, 4.73; HRMS–ESI (m/z):
[M + H]+ calcd for C12H10O3+, 202,0624; found, 202,0637.
Preprint
A non-peer-reviewed version of this article has been previously published
as a preprint doi:10.3762/bxiv.2020.49.v1
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