Influence of Anion-Binding Schreiner's Thiourea on DMAP Salts: Synergistic Catalysis toward the Stereoselective Dehydrative Glycosylation from 2-Deoxyhemiacetals

Glycosylation from 2 ‑Deoxyhemiacetals

Note

Inﬂuence of Anion-Binding Schreiner’s Thiourea on DMAP Salts:

Synergistic Catalysis toward the Stereoselective Dehydrative

Titli Ghosh, Ananya Mukherji, and Pavan K. Kancharla*

Cite This: https://dx.doi.org/10.1021/acs.joc.0c02473

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sı Supporting Information

ABSTRACT: Amines are used as additives to facilitate or increase the host−guest chemistry between the thiourea and the anions of

Bronsted acids. However, we here demonstrate, for the ﬁrst time, the synergistic eﬀect of the combination of DMAP/HCl/

Schreiner’s thiourea in catalyzing dehydrative glycosylation. The variations in the electronic eﬀects of the cationic Bronsted acid part

(

the protonated DMAP) in the presence of chloride binding Schreiner’s thiourea have been discussed using NMR and X-ray

crystallographic techniques.

ual hydrogen-bond donors that act akin to Lewis acids

tris(2,4,6-trimethoxyphenyl)phosphine (TTMPP) on glucose-

have garnered interest as alternatives for metal-based

derived donor.

Schreiner’s thiourea 1, with its ability to bind and stabilize

the anions, usually acts as a polarizing agent and makes the

cationic entity more reactive, allowing it to react with

nucleophiles, like in the case of glycosyl chlorides or

Lewis acids in synthetic organic chemistry. Recent times have

seen a surge in the utility of these dual hydrogen-bond donors

for their ability to bind to various anions. For example,

Schreiner’s thiourea 1 can strongly bind to various anions

12,13

phosphates.

Likewise, in the case of Bronsted acids, the

such as chloride, oxyanions, cyanide, and carboxylates,

acidity of the associated proton is enhanced in the presence of

allowing the catalysis of various organic transformations.

anion-binding host (Figure 1, a). The host−guest chemistry

Anion receptors also are useful as nontoxic anion-transporting

with the anions can be enhanced with quaternary ammonium

agents across cell membranes. This property of 1 has found

salts as cations. The addition of nitrogenous bases like

potential applicability in carbohydrate chemistry as well. The

same has been exploited toward the development of stereo-

selective glycosylation methods from glycosyl chlorides,

trichloroacetimidates, and glycals. McGarrigle showed that

Schreiner’s thiourea could catalyze the conversion of glycals

pyridines to trap the proton of the Bronsted acids can also

enhance the anion binding rate with urea/thiourea com-

pounds. However, the protonated species will also be

competitive binder to the anion. Intuitively, the nature of

newly formed host−guest anion is inﬂuenced by the cationic

protonated amine and, vice versa. The inﬂuence of anion

binding receptors on the reactivity of such acid−base pairs, like

pyridine hydrochloride or DMAP hydrochloride has not been

studied yet (Figure 1, b). As the proton is bound to DMAP, in

into the corresponding 2-deoxyglycosides. Schmidt and his

co-workers reported that O-glycosyl trichloroacetimidates

aﬀorded corresponding glycosides in the presence of 5 mol

of Brønsted acid and 1 as a co-catalyst. Recently, this

cooperative eﬀect of thiourea and an acid catalyst was reported

by Galan and co-workers with an increased substrate scope.

Received: October 19, 2020

The group demonstrated that the combination of 1 and chiral

BINOL phosphoric acid catalyst was eﬀective for the observed

catalysis. Ye et al. reported Koenigs−Knorr glycosylation by

urea-mediated hydrogen-bond activation, and anomeric

selectivity was observed to improve upon the addition of

XXXX American Chemical Society

The Journal of Organic Chemistry

J. Org. Chem. XXXX, XXX, XXX−XXX

Note

bind to the hydroxyl anion as well. However, when the

reaction was performed with 1 alone, it did not lead to the

formation of the coupled product. Thiourea 1 and DMAP

hydrochloride 3a work synergistically to facilitate the

glycosylation of lactols. As discussed vide supra, it is well

established that Schreiner’s thiourea binds to the chloride via a

dual hydrogen bonding and when mixed with an equimolar

amount of DMAP hydrochloride forms a ternary complex

leading to a new catalytic site. In other words, the presence of

the halide binding thiourea alters the reactivity of the cationic

Brønsted acid, in this case, the protonated DMAP. As

discussed above, DMAP hydrochloride salt 3a as a catalyst in

the presence of thiourea 1 as a cocatalyst provided

corresponding monosaccharide 6a under similar reaction

conditions in 87% yield (SI , Table S1, entry 1), whereas

primary sugar acceptor 5b gave e ﬃciently the corresponding

disaccharide 6b in 66% yield (SI , Table S1, entry 2). No

signiﬁcant improvements have been observed in the yields by

increasing the amount of thiourea 1 (SI , Table S1, entry 3).

When bis-thiourea 2, a stronger halide binding agent was

employed as a cocatalyst instead of thiourea 1, it resulted in the

formation of the undesired dimerized product 6j instead of the

desired product (SI , Table S1, entry 5). After a few more

optimization studies, 3a in the presence of 1 in DCE as a

solvent was chosen as the best system (SI , Table S1, entries 4−

Figure 1. Schreiner’s thiourea bound to neutral acids vs salts.

the ternary ion-pair complex of DMAP/HCl/Schreiner’s

thiourea (Figure 1, b), the inﬂuence of anion binding receptors

on the cationic part could be dependent on the strength of ion-

7a,16

pair interactions.

We were curious to understand, under

this scenario, whether the proton that is bound to DMAP, a

cationic Bronsted acid, will behave as a weaker or a stronger

acid under the inﬂuence of 1, relative to simple DMAPHCl.

The advantage of such a system lies in utilizing the strong

nucleophilicity of DMAP to control stereoselectivities in

glycosylation reactions after the proton transfer. In order to

understand the eﬀect of thiourea on DMAP hydrochloride, it is

important to design the conditions (solvents of low polarity

such as DCM) such that the salts exist as contact ion pairs and

not solvent-separated ion pairs, both in the presence and

absence of thiourea. We have chosen the more reactive 2-

deoxyhemiacetals as substrates to study the synergistic catalytic

activity.

13). Encouraged by the results, the scope of the methodology

has been examined for 2-deoxygalactosides. When the

tetraisopropyldisilyl-protected 2-deoxygalactopyranose 4b was

treated with benzyl alcohol, the coupled product was obtained

in 72% yield and 8:1 α/β selectivity. The donor 4b when

treated with other acceptors, including the sugar acceptors

(

5d−5g, Table 1, entries 2−5), the products were obtained in

moderate yields, albeit with exclusive α-selectivity. Also, the

reactions when performed with TBDPS-protected 3S,4R-

erythro-pyranose 4d with alcohols 5d, 5e, and 5h gave

eﬃciently the corresponding monosaccharides 7a−7c, respec-

tively, as their axial isomers in high yields (Table 2, entries 1−

3). Similarly, the coupling of TBDPS-protected donor 4d with

both glucose and galactose-derived acceptors 5b and 5g

provided corresponding disaccharides 7d and 7e in 75% and

65% yields, respectively, as axial isomers. TBDPS-protected

glucose-derived donor 4c reacted with acetonide protected

primary sugar acceptor 5f to provide the disaccharide 6h in

73% yield as 5:1 mixture of anomers (Table 3, entry 1).

However, the O-dibenzyl 2-deoxyribose hemiacetal 4e, when

reacted with the acceptor 5g, lead to 70% of the glycosylated

product 6i as 1:1 anomers, with a complete loss of

stereocontrol presumably due to high stability and reactivity

-Deoxysugars are part of several natural products, anti-

biotics, and cancer agents and are thus involved in several

biological processes. There are numerous methods for the

synthesis of 2-deoxyglycosides emanating from glycosyl

acetimidates, thioglycosides, halides, enol ethers, and

hemiacetals. Jacobsen and his group discovered macrocyclic

chiral bis-thiourea that catalyzes the stereospeciﬁc glycosyla-

tion reaction of glycosyl chloride to aﬀord corresponding

products in high yields. In continuation of our eﬀorts to

develop organocatalytic methods toward the synthesis of 2-

deoxyglcosides, we focused our attention on dehydrative

glycosylations. Wang and co-workers reported that DMAP

hydrochloride 3a reacts with acyl chlorides to generate a

DMAP-acylium intermediate that reacts with alcohols to form

of furanosyl oxocarbeniums ions, that favors S 1 pathway.

esters.

In order to assess the inﬂuence of thiourea on the structural

diﬀerences and, in turn, the Bronsted acidic ability of the

protonated DMAP, attempts were made to grow a cocrystal of

DMAP·HCl and Schreiner’s thiourea. Fortunately, we were

successful in obtaining the cocrystal in dichloromethane/

pentane solvent system. XRD data of cocrystal (1:1 3a/1)

reveals a hydrogen bonding between thiourea 1 and the

Taking a cue from above, we were curious to examine

whether DMAP hydrochloride 3a would react with the reactive

-deoxyhemiacetals 4, leading to the formation of DMAP-

glycosylated cation following the elimination of water

molecule, which in turn can undergo stereoselective glyco-

sylation with alcohols. However, this experiment, when

performed, could not catalyze the dehydrative glycosylation

chloride ion of DMAP salt 3a (Figure 2). In addition, the N −

(SI , Scheme S1a). Intriguingly, the reaction, when performed

H bond length is shorter in the cocrystal as compared to that

under similar conditions in the presence of 20 mol % of

DMAPHCl along with 20 mol % of Schreiner’s thiourea 1, led

to the conversion of the lactol 4a into glycosylated product 6a

at 40 °C, eﬃciently (SI, Table S1, entry 1). It is not unusual to

think that 1 can itself catalyze the reaction given its ability to

of DMAP·HCl salt 3a (N −H : 0.860 Å in cocrystal and N −

H : 1.083 Å in 3a, Figure 2). Hence, it implies that the

negative charge of chloride ion is distributed between the

Schreiner’s thiourea and the protonated DMAP, which resulted

in shrinkage of the N −H bond length. Moreover, there was

J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry

Note

Table 1. Glycosylation of Cyclic Silyl-Protected D-Galactosyl

Donor with Various Glycosyl Acceptors

Table 2. Glycosylation of TBDPS-Protected D-Arabinosyl

Donor with Various Glycosyl Acceptors

Reaction conditions: 0.09 mmol of 4b, 0.11 mmol of acceptor 5c−g.

Reaction conditions: 0.08 mmol of 4d, 0.09 mmol of acceptor 5b,

d−g.

also a change in the bond distances of the C−H and CS

bonds of the cocrystal relative to the XRD of Schreiner’s

thiourea alone (Figure 2). This is also in line with the

observations of Schreiner and co-workers that the Lewis base,

Table 3. Glycosylation with 2-Deoxyglucose- and 2-

Deoxyribose-Derived Donors

−

i.e., Cl , is in H-bonding with C−H along with the N−H’s of

There is a signiﬁcant change in the dihedral angle also, of 1,

in the presence of the salt 3a. A similar interaction between 3a

and 1 has been observed in the solution state as well. H NMR

titration experiments of DMAP hydrochloride 3a with

increasing equivalents of thiourea 1 led to a gradual shift in

the chemical shift of the N−H peak H of 3a from δ 15.36

ppm to δ 13.92 ppm (Figure 3B), indicating the shortening of

the N−H bond in the presence of 1. Besides, there is nearly

.43 ppm shift in the chemical shift of N−H protons of

thiourea H (from δ 11.02 ppm to δ 10.59 ppm). This signiﬁes

that the ternary complex between the salt 3a and thiourea 1 is

intact in the solution phase as well. On the other hand, when

equimolar 2-propanol was mixed with 3a in the absence of

thiourea 1, a slight shift in the N−H was observed along with a

shift of the O−H (H , δ 1.24 to 2.24 ppm) and

nonexchangeable C−H (H , δ 3.96 to 3.98 ppm) protons of

the alcohol, indicating a weak interaction between the cationic

DMAPH and the oxygen of the 2-propanol (Figure 3A). It is

Besides, there is an interaction of the ternary complex (3a.1)

with the alcohol 5a also. We hypothesized that thiourea 1

bound to chloride with its negative charge stabilized via

delocalization could be behaving as a weakly coordinating

anion, thus increasing the Lewis acidic activity of the cationic

also known that thiourea 1 can exist in hydrogen bonding with

alcohol. However, when an equimolar amount of thiourea 1

was added to this mixture, the shift in H (H , δ 1.24 to 1.76

ppm) and H (δ 3.96 to 3.97 ppm) though moderate, is

present, whereas the shift in H is signiﬁcant (Figure 3A). This

DMAPH . In order to decipher the same, we separately

reinstates the fact the chloride ion is a stronger Lewis base than

the alcohol and can bind strongly to thiourea (Figure 3).

synthesized a protonated DMAP salt with a weakly

coordinating BArF as the counterion.

The Journal of Organic Chemistry

J. Org. Chem. XXXX, XXX, XXX−XXX

Note

Figure 2. (a) XRD structure of DMAP·HCl·2H O. (b) ORTEP diagram of the ternary complex DMAP/HCl/Schrenier’s thiourea (ellipsoid

−

contours are at 30% probability level). (c) Two units symmetrically held by two chloride ions (N−H···Cl interactions with DMAP are also

shown).

Based on the XRD data of the ternary complex, the NMR

studies, and the control experiments, we propose that the

ternary complex, donor and the acceptor might be involved in

a loose (exploded) transition state (Scheme 1, path a, T.S.),

Scheme 1. Proposed Mechanism for Cooperative Catalysis

of DMAP Salt and Thiourea

Figure 3. (A) H NMR experiment of 3a and 1 with 2-propanol. (B)

where the cationic DMAPH coordinates to the equatorial

H NMR titration of 3a with 1 in 0.6 mL of solution of CDCl₃.

isomer of the hemiacetal, whereas, the polarized sulfur activates

the acceptor, thus leading to the formation of the axially

glycosylated products. The equatorial isomer of the anomeric

alcohol that is more nucleophilic than the axial isomer may

preferentially lead to the axial glycosylated products (Scheme

1, path a). Alternatively, the ternary complex reacting with the

anomeric hemiacetal might lead to the formation of equatorial

DMAP-glycosylated cationic species (Scheme 1, I) with the

expulsion of a water molecule, that may undergo an S 2-

displacement leading to axial coupled products (Scheme 1,

path b). However, further experiments need to be performed

Interestingly, the N−H peak of DMAPH·BArF 3e appears at

around δ 13.24 ppm (in DMSO-d ), closer to the N−H peak

of 3a in the presence of 1, conﬁrming its poor Bornsted acidic

ability. However, when the reaction between donor 4a and the

acceptor 5b in the presence of the BArF salt 3e, no coupled

product was obtained even after 24 h (SI, Scheme S1b). Also,

when a 3.5:1 α/β mixture of 7a was subjected to the standard

conditions, it did not lead to any change in selectivity even

after 24 h, suggesting the kinetic origins of the product.

J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry

Note

to decipher the mechanism of activation of the current

organocatalytic method.

17.2, 13.8, 13.5, 13.4, 13.4, 13.3, 12.8. HRMS (ESI) m/z: [M +

NH ] calcd for C H O Si NH 528.2813, found 528.2809.

25 42

,4,6-Tri-O-tert-butyldiphenylsilyl-2-deoxy-α,β-D-glucopyranose

4c). TBDPS-protected D-glucal (900 mg, 1.05 mmol, 1equiv)

dissolved in 10 mL of DCM. Then TTBP hydrochloride (298 mg,

In conclusion, the synergistic activity of Schreiner’s thiourea

and DMAP salts allowed us to perform the dehydrative

glycosylation under ambient conditions. The current cooper-

ative catalysis method is mild enough to activate only 2-deoxy

sugar hemiacetals selectively and does not support the

glycosylation of 2-oxy sugars. While this operational friendly

protocol with benchtop chemicals for the stereoselective

synthesis of 2-deoxysugars could be of great utility to

carbohydrate chemistry, the underlying concept of this unique

cocatalysis of DMAP salts in the presence of Schreiner’s

thiourea could ﬁnd its applicability in the catalysis of various

organic transformations.

(

.05 mmol, 1 equiv) was added, and this solution was stirred at rt for

2 h. The reaction mixture extracted with DCM (3 × 20 mL). The

organic phase was washed with brine (80 mL), dried over anhydrous

Na SO , and concentrated under reduced pressure. The crude was

puriﬁed by column chromatography in an ethyl acetate/hexane

solvent system to give the product as a white solid 4c. R : 0.3 (10%

ethyl acetate in hexane), amount 400 mg, yield 43%. H NMR (600

MHz, CDCl ): δ 7.64 (d, J = 6.8 Hz, 2H), 7.54 (dd, J = 13.5, 6.9 Hz,

H), 7.41−7.27 (m, 20H), 7.16 (q, J = 7.4 Hz, 4H), 5.01 (t, J = 6.4

Hz, 1H), 4.11 (d, J = 4.6 Hz, 1H), 4.02 (dd, J = 11.0, 7.9 Hz, 1H),

.90 (d, J = 2.4 Hz, 1H), 3.71 (s, 1H), 3.63 (dd, J = 11.1, 4.7 Hz, 1H),

.46 (d, J = 6.4 Hz, 1H), 1.74 (ddd, J = 12.1, 9.4, 2.6 Hz, 1H), 1.51

(

d, J = 13.4 Hz, 1H), 0.99 (s, 9H), 0.93 (s, 9H), 0.79 (s, 9H).

EXPERIMENTAL SECTION

■

C{ H} NMR (151 MHz, CDCl ): δ 136.0, 135.9, 135.88, 135.8,

General Information. All solvents and reagents used were in

commercial grade for reaction without further puriﬁcation. Reagents

were purchased from Sigma-Aldrich, Merck, Spectrochem, Carbo-

synth, and Chempure.

Analysis. Reactions monitored by TLC on Kieselgel 60 F254

Merck). Detection was done by examination under UV light (254

nm) and by charring with 10% sulfuric acid in water. Puriﬁcation was

performed by both ultra high performance liquid chromatography

UHPLC) using column [Particle size: (μ) 12, Dim: (mm) 250 × 10]

in reverse phase and in normal phase using silica gel (Merck, 60−120

mesh). Extracts were concentrated in vacuo using both a Buchi rotary

35.8, 135.7, 133.9, 133.8, 133.6, 133.4, 133.1, 129.9, 129.8, 129.8,

29.7, 129.6, 127.9, 127.9, 127.7, 127.7, 88.4, 81.1, 71.2, 68.9, 62.8,

₅_.₁_,₂₇_.₀_,₂₇_.₀_,₂₇_.₀_,₁₉_.₃_,₁₉_.₀_._H_R_M_S₍_E_S_I₎_m_/_z_:_[_M₊_N_a_]+ calcd

for C H O Si Na 901.4110, found 901.4112.

,4-Bis(O-tert-butyldiphenylsilyl)-α,β-D-arabinose (4d). The pro-

(

cedure for the synthesis of 1e was similar to the procedure for 1d with

TBDPS-protected D-arabinal (500 mg, 0.84 mmol, 1 equiv) taking

TTBP hydrochloride (48 mg, 0.17 mmol, 20 mol %) as the starting

material to aﬀord a sticky white solid 4d. R : 0.2 (10% in ethyl acetate

in hexane), amount 430 mg, yield 84%, α/β = 0.7:1. H NMR (400

MHz, CDCl ): δ 7.73−7.61 (m, 12H), 7.46−7.22 (m, 22H), 5.20 (d,

J = 1.2 Hz 1H), 4.68 (s, 1H), 4.17 (s, 2H), 3.98 (dd, J = 11.2, 8.2 Hz,

(

evaporator (bath temperatures up to 40 °C) at a pressure of either 15

mmHg (diaphragm pump) and 0.7 mmHg (oil pump), at rt. H and

C NMR were recorded on a Bruker 600 and 400 MHz spectrometer

H), 3.79−3.78 (m, 1H), 3.68−3.66 (m, 1H), 3.60−3.56 (m, 1H),

.43 (d, J = 9.7 Hz, 1H), 3.09 (dd, J = 11.7, 3.2 Hz, 1H), 2.10 (t, J = 4

using CDCl as solvent. Chemical shift values reported in ppm with

Hz, 1H), 2.03−1.98 (m, 1H), 1.54 (d, J = 13.6 Hz, 1H), 1.26 (s, 1H),

13 1

the solvent as the internal standard (CDCl : δ 7.26 for H, δ 77.16 for

C). Data are reported as follows: chemical shifts (δ), multiplicity (s

singlet, d = doublet, dd = double of doublet, ddd = doublet of

1.10 (s, 15H), 1.07 (s, 9H), 1.00 (s, 7H). C{ H} NMR (101 MHz,

CDCl ): δ 136.3, 136.1, 136.1, 136.1, 136.0, 134.5, 134.3, 134.0,

33.9, 133.6, 133.5, 133.1, 132.8, 130.2, 130.0, 129.9, 129.9, 129.9,

29.7, 129.7, 128.0, 127.8, 127.8, 127.7, 127.7, 127.7, 92.8, 92.7, 71.9,

1.0, 70.2, 68.8, 63.9, 36.6, 27.3, 27.2, 27.1, 27.1, 19.5, 19.4, 19.3,

7.6, 17.6, 17.4, 17.3, 17.3. HRMS (ESI) m/z: [M + Na] ⁺calcd for

doublet of doublets, dt = doublet of triplet, t = triplet, td = triplet of

doublet, q = quartet, m = multiplet) etc., coupling constants J (Hz),

and integration. High resolution mass measurements were performed

using an Agilent Technologies mass spectrometer. Single-crystal XRD

was recorded on a Bruker Nonius Smart Apex II X-ray single-crystal

diﬀractometer (CCD). The diastereomeric ratio calculated from

crude NMR. Speciﬁc rotation was recorded on a Rudolph Research

Analytical polarimeter; the units of the speciﬁc rotation are (deg·

mL)/(g·dm) and concentration c is given in g/100 mL.

Procedure for Crystal Growth. An equimolar mixture of 3a and 1

was taken in a glass vial and was dissolved in a minimum volume of

DCM solvent. To the solution was added n-pentane dropwise (twice

the volume of DCM) through the walls of the vial. The solution was

kept open at room temperature for 2 days, allowing the slow

evaporation of the solvents when the XRD quality crystals were

obtained.

C H O Si Na 633.2827, found 633.2821.

-Dimethylaminopyridinium Hydrochloride Salt (3a). Methanol

(

2 mL) was taken in round-bottom ﬂask and stirred in an ice bath

under argon. Then 2 mL of acetyl chloride added dropwise to it. After

few minutes, an ether (1 mL) solution of DMAP (500 mg, 4.09 mmol,

equiv) was added dropwise and the mixture stirred at 0 °C under

argon. After 1 h, it was concentrated under reduced pressure to aﬀord

the solid. It was washed with ether (3 × 10 mL) to obtain white solid

a. Amount 626 mg, yield 97%. H NMR (600 MHz, CDCl ): δ

5.35 (br s, 1H), 8.14 (t, J = 6.5 Hz, 2H), 6.77 (d, J = 6.8 Hz, 2H),

.27 (s, 6H). C{ H} NMR (151 MHz, CDCl ): δ 157.4, 139.0,

06.9, 40.4.2. HRMS (ESI) m/z: [M + H] calcd for C H N H

23.0917, found 123.0924.

-Dimethylaminopyridinium Tosylate Salt (3b). p-Toluenesul-

,6-Di-O-(tetraisopropyldisiloxane-1,3-diyl)-3-O-benzoyl-2-

deoxy-α,β-D-galactopyranoside (4b). To the ice-cold solution of 4,6-

di-O-tetraisopropylsiloxane protected D-galactal (4.1 g, 0.01 mol, 1

equiv) was slowly added pyridine (1.6 g, 1.6 mL, 0.020 mol, 1.5

equiv) followed by benzoyl chloride (2.8 g, 2.3 mL, 0.020 mol, 1.0

equiv) and the mixture stirred in DCM (20 mL) overnight at rt. The

reaction mixture was concentrated under reduced pressure, and the

product 4b was puriﬁed by ﬂash column chromatography as a

fonic acid (779 mg, 4.09 mmol, 1 equiv) was dissolved in 5 mL of

DCM and a few drops of methanol. Then, DMAP (500 mg, 4.09

mmol, 1 equiv) was added pinch wise to it and it was stirred at 0 °C

under argon. After 2 h, it was concentrated under reduced pressure to

get the solid. It was washed with ether (3 × 10 mL) to aﬀord white

solid 3b. Amount 1.24 g, yield 98%. H NMR (600 MHz, CDCl ): δ

14.21 (br s, 1H), 8.20 (t, J = 6.5 Hz, 2H), 7.81 (d, J = 8.0 Hz, 2H),

yellowish solid. R : 0.5 (20% ethyl acetate in hexane), amount 1.6 g,

7.16 (d, J = 7.9 Hz, 2H), 6.74 (d, J = 6.9 Hz, 2H), 3.19 (s, 6H), 2.34

yield 31%, α/β = 1:0.5. H NMR (400 MHz, CDCl ): δ 8.04 (d, J =

(s, 3H). C{ H} NMR (151 MHz, CDCl ): δ 157.4, 142.5, 140.0,

.2 Hz, 2H), 7.55 (t, J = 7.4 Hz, 1H), 7.46−7.41 (m, 2H), 5.57−5.51

139.8, 128.9, 126.1, 106.9, 40.2, 21.4. HRMS (ESI) m/z: [M + H]

(

m, 1H), 5.45 (d, J = 3.3 Hz, 1H), 4.50 (s, 1H), 4.40−4.37 (m, 1H),

calcd for C H N H 123.0917, found 123.0918.

.20 (dd, J = 9.9, 5.8 Hz, 1H), 3.87−3.74 (m, 2H), 2.41 (td, J = 12.4,

-Dimethylaminopyridinium Hydrotetrakis[3,5 bis-

.5 Hz, 1H), 1.92 (dd, J = 12.3, 4.6 Hz, 1H), 1.11−0.89 (m, 28H).

(triﬂuoromethyl)phenyl]borate Salt (3e). DMAP hydrochloride salt

(100 mg, 0.630 mmol, 1.0 equiv) and sodium tetrakis[3,5-

bis(triﬂuoromethyl)phenyl]borate (559 mg, 0.630 mmol, 1.0 equiv)

were dissolved in 2 mL of DCM. After that, it was stirred at 0 °C for 1

C{ H} NMR (101 MHz, CDCl ): δ 166.4, 133.29, 133.1, 130.5,

30.2, 130.0, 129.9, 128.4, 128.3, 94.6, 92.7, 74.6, 72.1, 70.1, 69.7,

5.7, 64.5, 59.8, 59.6, 33.6, 30.2, 17.6, 17.5, 17.5, 17.5, 17.4, 17.3,

J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry

Note

h, and immediately a white precipitate of sodium chloride (NaCl) was

observed. Then, the solution was allowed to settle down for few min

and after decant the solution, the solution part was then concentrated

obtain product 6c as a colorless liquid. R : 0.8 (20% ethyl acetate in

hexane), amount 42 mg, yield 72%. α/β= 8:1. α-anomer: H NMR

(400 MHz, CDCl ): δ 8.03 (d, J = 7.2 Hz, 2H), 7.55 (t, J = 7.3 Hz,

under reduced pressure to get a white solid 3e. Amount 572 mg, yield

1H), 7.42 (t, J = 7.8 Hz, 2H), 7.38−7.27 (m, 5H), 5.51 (ddd, J = 12.6,

4.5, 2.6 Hz, 1H), 5.07 (d, J = 3.3 Hz, 1H), 4.70 (d, J = 11.9 Hz, 1H),

4.52 (s, 1H), 4.48 (d, J = 12.0 Hz, 1H), 4.04 (dd, J = 9.9, 5.6 Hz, 1H),

3.88−3.77 (m, 2H), 2.45 (td, J = 12.4, 3.7 Hz, 1H), 1.96 (d, J = 5.0

2%. H NMR (400 MHz, DMSO): δ 13.24 (s, 1H), 8.26 (d, J = 7.7

Hz, 2H), 7.72 (s, 4H), 7.66 (s, 8H), 7.02 (d, J = 7.7 Hz, 2H), 3.22 (s,

H). ¹³C{ H} NMR (101 MHz, DMSO): δ 139.1, 134.1, 125.3,

22.6, 107.0. HRMS (ESI) m/z: [M + H] calcd for C H N H

23.0917, found 123.0920.

Hz, 1H), 1.11−1.02 (m, 24H), 0.89−0.87 (m, 4H). C{ H} NMR

(101 MHz, CDCl ): δ 166.5, 137.8, 133.1, 130.5, 129.9, 128.6, 128.4,

N,N′-Bis(3,5-bis(triﬂuoromethyl)phenyl)thiourea (1). A mixture of

,5-bis(triﬂuoromethyl)phenyl isothiocyanate (68 μL, 0.37 mmol),

,5-bis(triﬂuoromethyl)aniline (58 μL, 0.37 mmol) and 50 μL of

128.3, 127.9, 127.8, 97.0, 70.3, 70.1, 69.1, 65.6, 59.8, 31.1, 17.6, 17.5,

17.5, 17.4, 17.3, 17.2, 13.8, 13.5, 13.3, 12.8. HRMS (ESI) m/z: [M +

NH₄] calcd for C H O Si NH 618.3282, found 618.3277. [α]

methanol was stirred for 30 min.1 The solution was concentrated

under reduced pressure to get white solid. The product scraped oﬀ

the walls of the round bottomed ﬂask aﬀording thiourea 1 in

+21 (c 0.06, CHCl₃).

Allyl 4,6-Di-O-(tetraisopropyldisiloxane-1,3-diyl)-3-O-benzoyl-2-

deoxy-α-D-galactopyranoside (6d). The general procedure was

followed by adding glycosyl donor 4b (51 mg, 0.099 mmol, 1.0

equiv), DMAP hydrochloride catalyst 3a (3 mg, 0.016 mmol, 20 mol

%), thiourea 1 (8 mg, 0.016 mmol, 20 mol %), and acceptor allyl

alcohol 5d (12 mg, 14 μL, 0.090 mmol, 1.1 equiv) at 40 °C for 24 h

quantitative yield. H and C{ H} NMR matched with reported

data.

,1′-(1,2-Phenylene)bis(3-phenylthiourea) (2). The procedure for

was similar to that of 1 and used a mixture of 3,5-

bis(triﬂuoromethyl)phenyl isothiocyanate (168 μL, 0.62 mmol), o-

phenylenediamine (50 mg, 0.46 mmol), and 100 μL of methanol to

to obtain product 6d as a colorless liquid. R

hexane), amount 36 mg, yield 66%. Selectivity α,α-anomer: H NMR

(400 MHz, CDCl ): δ 8.03 (d, J = 7.2 Hz, 2H), 7.55 (t, J = 7.4 Hz,

: 0.3 (10% ethyl acetate in

aﬀord thiourea 2 in quantitative yield. H and C{ H} NMR

matched with reported data.

1H), 7.43 (t, J = 7.7 Hz, 2H), 5.91 (ddt, J = 16.3, 10.7, 5.6 Hz, 1H),

5.49 (ddd, J = 12.5, 4.5, 2.6 Hz, 1H), 5.30 (dd, J = 10.2, 1.7 Hz, 1H),

5.19 (dd, J = 10.4, 1.6 Hz, 1H), 5.02 (d, J = 2.9 Hz, 1H), 4.50 (s, 1H),

4.15 (ddt, J = 12.9, 5.1, 1.6 Hz, 1H), 4.01−3.94 (m, 2H), 3.86−3.75

(m, 2H), 2.44 (td, J = 12.4, 3.6 Hz, 1H), 1.91 (dd, J = 12.2, 4.5 Hz,

General Procedure. Glycosyl donor (0.06−0.16 mmol, 1 equiv)

and glycosyl acceptor (1.1 equiv) were taken in a round-bottomed

ﬂask and dissolved in 0.5 mL (for 0.06 mmol) of DCE. Then catalyst

and thiourea were added and heated at 40 °C (using an oil bath) for

8−24 h. After being cooled to rt, the reaction mixture was quenched

1H), 1.11−1.03 (m, 24H), 0.89−0.87 (m, 4H). C{ H} NMR (101

MHz, CDCl ): δ 166.4, 134.4, 133.1, 130.5, 129.9, 128.3, 117.2, 97.1,

70.2, 70.0, 68.2, 65.6, 59.8, 30.2, 17.6, 17.6, 17.5, 17.5, 17.4, 17.4,

by water (1 mL for 0.06 mmol) and extracted with DCM (3 × 15 mL

for 0.06 mmol), dried over Na SO , concentrated under reduced

pressure. and puriﬁed by column chromatography in hexane/ethyl

acetate.

Isopropyl 3,4,6-Tri-O-benzyl-2-deoxy-α,β-D-glucopyranoside

6a). The general procedure was followed by adding glycosyl donor

17.3, 17.2, 13.8, 13.5, 13.3, 12.8. HRMS (ESI) m/z: [M + NH ]

calcd for C28

H O Si NH 568.3126, found 568.3145. [α] = +6 (c

46 7 2 4 D

0.12, CHCl ).

(

Propargyl 4,6-Di-O-(tetraisopropyldisiloxane-1,3-diyl)-3-O-ben-

zoyl-2-deoxy-α-D-galactopyranoside (6e). General procedure was

followed by adding glycosyl donor 4b (50 mg, 0.097 mmol, 1.0

equiv), DMAP hydrochloride catalyst 3a (3 mg, 0.020 mmol, 20 mol

%), thiourea 1 (10 mg, 0.020 mmol, 20 mol %), and acceptor

propargyl alcohol 5e (6 mg, 8 μL, 0.110 mmol, 1.1 equiv) at 40 °C for

a (50 mg, 0.12 mmol, 1 equiv), DMAP hydrochloride, catalyst 3a (4

mg, 0.024 mmol, 20 mol %), thiourea 1 (12 mg, 0.024 mmol, 20 mol

), and glycosyl acceptor 2-propanol (11 mg, 14 μL, 0.18 mmol, 1.5

equiv) at 40 °C for 18 h to obtain product 6a as a colorless liquid. R :

0.9 (20% ethyl acetate in hexane), amount 50 mg, yield 87%. H

NMR (600 MHz, CDCl ): δ 7.36−7.16 (m, 17H), 5.08 (d, J = 2.8

24 h to obtain product 6e as a colorless liquid. R : 0.3 (10% ethyl

Hz, 1H), 4.90−4.88 (m, 1H), 4.67 (d, J = 3.0 Hz, 1H), 4.65 (d, J =

acetate in hexane), amount 45 mg, yield 85%. Selectivity α,α-anomer:

.4 Hz, 1H), 4.52−4.50 (m, 2H), 4.01 (ddd, J = 11.5, 8.9, 5.1 Hz,

H), 3.89−3.87 (m, 1H), 3.81 (ddd, J = 14.1, 6.9, 2.8 Hz, 2H), 3.67−

.61 (m, 2H), 2.24 (ddd, J = 12.8, 5.0, 1.2 Hz, 1H), 1.74 (ddd, J =

2.8, 11.6, 3.7 Hz, 1H), 1.26 (d, J = 6.2 Hz, 1H), 1.16 (d, J = 6.3 Hz,

H NMR (400 MHz, CDCl ): δ 8.03 (d, J = 7.3 Hz, 2H), 7.56 (t, J =

7.4 Hz, 1H), 7.43 (t, J = 7.6 Hz, 2H), 5.46 (ddd, J = 12.6, 4.5, 2.5 Hz,

1H), 5.18 (d, J = 3.5 Hz, 1H), 4.50 (s, 1H), 4.22 (t, J = 2.1 Hz, 2H),

3.98 (dd, J = 9.9, 5.8 Hz, 1H), 3.86−3.76 (m, 2H), 2.48 (dd, J = 12.5,

3.7 Hz, 1H), 2.43 (t, J = 2.2 Hz, 1H), 1.94 (d, J = 5.2 Hz, 1H), 1.11−

3H), 1.12 (d, J = 6.1 Hz, 3H). C{ H} NMR, HRMS, and optical

rotation value were matched with reported data.

1.02 (m, 24H), 0.89−0.87 (m, 4H). C{ H} NMR (101 MHz,

(

3,4,6-Tri-O-benzyl-2-deoxy-α,β-D-glucopyranosyl)-(1→6)-

CDCl ): δ 166.4, 133.1, 130.4, 129.9, 128.3, 96.6, 79.4, 74.5, 70.4,

,2:3,4-di-O-isopropylidene-α-D-galactopyranoside (6b). The gen-

69.9, 65.5, 59.7, 54.3, 29.8, 17.6, 17.5, 17.5, 17.4, 17.4, 17.4, 17.3,

eral procedure was followed by adding glycosyl donor 4a (50 mg, 0.12

mmol, 1 equiv), DMAP hydrochloride catalyst 3a (4 mg, 0.024 mmol,

17.2, 13.9, 13.8, 13.7, 13.4, 13.3, 12.8. HRMS (ESI) m/z: [M + NH ]

calcd for C H O Si NH 566.2969, found 566.2959. [α] = +27

0 mol %), thiourea 1 (12 mg, 0.024 mmol, 20 mol %), and glycosyl

(

c 0.08, CHCl₃).

4,6-Di-O-tetraisopropyldisiloxane-1,3-diyl-3-O-benzoyl-2-

acceptor 5f (34 mg, 0.13 mmol, 1.1 equiv) at 40 °C for 24 h to obtain

product 6b as a colorless liquid. R : 0.4 (20% ethyl acetate in hexane),

amount 61 mg, yield 66%. α/β = 4:1. H NMR (600 MHz, CDCl ): δ

(

deoxy-α-D-galactosyl)-(1→ 6)-1,2:3,4-di-O-isopropylidene-α-D-gal-

actopyranoside (6f). The general procedure was followed by adding

glycosyl donor 4b (51 mg, 0.099 mmol, 1.0 equiv), DMAP

hydrochloride catalyst 3a (3 mg, 0.020 mmol, 20 mol %), thiourea

1 (10 mg, 0.020 mmol, 20 mol %), and glycosyl acceptor 5f (28 mg,

0.110 mmol, 1.1 equiv) at 40 °C for 24 h to obtain product 6f as a

.37−7.21 (m, 36H), 4.99 (t, J = 6.7 Hz, 1H), 4.92 (d, J = 11.2 Hz,

H), 4.87 (d, J = 11.1 Hz, 1H), 4.79 (dd, J = 11.4, 7.0 Hz, 2H), 4.69−

.64 (m, 2H), 4.62−4.58 (m, 3H), 4.56−4.53 (m, 2H), 4.47 (t, J =

.7 Hz, 1H), 4.40 (d, J = 12.1 Hz, 1H), 3.99 (t, J = 9.3 Hz, 1H), 3.93

(

ddd, J = 11.6, 8.8, 4.9 Hz, 1H), 3.81 (dd, J = 11.4, 4.4 Hz, 1H),

colorless liquid. R : 0.3 (10% ethyl acetate in hexane), amount 42 mg,

.74−3.71 (m, 1H), 3.66 (ddd, J = 16.4, 5.9, 2.8 Hz, 1H), 3.61−3.47

yield 58%. Selectivity α,α-anomer: H NMR (400 MHz, CDCl ): δ

(

m, 6H), 3.34 (s, 3H), 2.321−2.28 (m, 1H), 1.71−1.66 (m, 1H).

8.03 (d, J = 7.1 Hz, 2H), 7.56 (t, J = 7.4 Hz, 1H), 7.43 (t, J = 7.7 Hz,

2H), 5.53 (d, J = 5.0 Hz, 1H), 5.46 (ddd, J = 12.4, 4.5, 2.6 Hz, 1H),

5.03 (d, J = 3.3 Hz, 1H), 4.62 (dd, J = 8.0, 2.4 Hz, 1H), 4.49 (s, 1H),

4.32 (dd, J = 5.1, 2.4 Hz, 1H), 4.28 (dd, J = 8.0, 1.9 Hz, 1H), 4.00−

3.95 (m, 2H), 3.85−3.73 (m, 3H), 3.65 (dd, J = 10.0, 7.7 Hz, 1H),

2.41 (td, J = 12.3, 3.7 Hz, 1H), 1.93 (dd, J = 12.3, 4.5 Hz, 1H), 1.57

(s, 3H), 1.44 (s, 3H), 1.34 (s, 6H), 1.10−1.02 (m, 24H), 0.88−0.87

C{ H} NMR, HRMS, and optical rotation value were matched with

reported data.

Benzyl 4,6-Di-O-(tetraisopropyldisiloxane-1,3-diyl)-3-O-benzoyl-

-deoxy-α-D-galactopyranoside (6c). General procedure was fol-

lowed by adding glycosyl donor 4b (50 mg, 0.097 mmol, 1.0 equiv),

DMAP hydrochloride catalyst 3a (3 mg, 0.020 mmol, 20 mol %),

thiourea 1 (10 mg, 0.020 mmol, 20 mol %), and acceptor benzyl

alcohol 5c (12 mg, 12 μL, 0.110 mmol, 1.1 equiv) at 40 °C for 24 h to

(m, 4H). C{ H} NMR (101 MHz, CDCl ): δ 166.5, 133.1, 130.5,

129.9, 128.3, 109.4, 108.8, 98.0, 96.5, 71.0, 70.9, 70.8, 70.2, 70.1, 66.1,

J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry

Note

5.8, 65.5, 59.8, 30.1, 26.3, 26.2, 25.1, 24.7, 17.6, 17.5, 17.5, 17.4,

Allyl 3,4-Bis(O-tert-butyldiphenylsilyl)-2-deoxy-β-D-arabinoside

(7a). The general procedure was followed by adding glycosyl donor

4d (50 mg, 0.08 mmol, 1 equiv), DMAP hydrochloride catalyst 3a (3

mg, 0.016 mmol, 20 mol %), thiourea 1 (8 mg, 0.016 mmol, 20 mol

%), and allyl alcohol acceptor 5d (5 mg, 6 μL, 0.09 mmol, 1.1 equiv)

7.3, 17.2, 13.8, 13.4, 13.3, 12.9. HRMS (ESI) m/z: [M + NH ]

calcd for C H O Si NH 770.3967, found 770.3960. [α] = +14 (c

60 12

0.10, CHCl₃).

Methyl 2,3,4-Tri-O-benzyl-6-O-(4,6-di-O-tetraisopropyldisilox-

ane-1,3-diyl-3-O-benzoyl-2-deoxy-α-D-galactosyl)-α-D-galactopyr-

anoside (6g). The general procedure was followed by adding glycosyl

donor 4b (49 mg, 0.096 mmol, 1.0 equiv), DMAP hydrochloride

catalyst 3a (3 mg, 0.020 mmol, 20 mol %), thiourea 1 (10 mg, 0.020

mmol, 20 mol %), and glycosyl acceptor 5h (51 mg, 0.090 mmol, 1.1

equiv) at 40 °C for 24 h to obtain product 6g as a colorless liquid. R_f:

at 40 °C for 24 h to obtain product 7a as a colorless liquid. R : 0.6

(10% ethyl acetate in hexane), amount 44 mg, yield 85%. Selectivity

α,α-anomer: H NMR (600 MHz, CDCl ): δ 7.72 (d, J = 7.3 Hz,

4H), 7.67 (d, J = 6.9 Hz, 2H), 7.60 (d, J = 7.4 Hz, 2H), 7.42−7.37

(m, 4H), 7.36−7.32 (m, 4H), 7.27 (m, 4H), 5.75−5.68 (m, 1H), 5.04

(d, J = 5.5 Hz, 1H), 5.01 (s, 1H), 4.82 (t, J = 3.4 Hz, 1H), 4.16 (d, J =

9.3 Hz, 1H), 3.97 (dd, J = 14.4, 4.4 Hz, 1H), 3.83 (s, 1H), 3.75 (dd, J

= 13.8, 5.2 Hz, 1H), 3.44 (s, 1H), 3.35 (dd, J = 11.7, 2.0 Hz, 1H),

2.19 (s, 1H), 1.43 (dt, J = 12.8, 3.7 Hz, 1H), 1.10 (s, 9H), 1.08 (s,

.3 (10% ethyl acetate in hexane), amount 37 mg, yield 40%.

Selectivity α,α-anomer: H NMR (400 MHz, CDCl ): δ 7.98−7.19

(m, 20H), 5.31 (ddd, J = 12.5, 4.5, 2.7 Hz, 1H), 4.88 (d, J = 11.7 Hz,

1H), 4.83−4.78 (m, 1H), 4.75−4.69 (m, 2H), 4.64−4.59 (m, 2H),

4.52 (d, J = 11.7 Hz, 1H), 4.38 (s, 1H), 3.98 (dd, J = 9.9, 3.6 Hz, 1H),

3.91−3.86 (m, 2H), 3.84−3.82 (m, 1H), 3.79−3.73 (m, 2H), 3.72−

3.64 (m, 2H), 3.55 (dd, J = 9.3, 5.6 Hz, 1H), 3.34 (s, 3H), 3.31 (dd, J

9H). C{ H} NMR (151 MHz, CDCl ): δ 136.2, 136.2, 136.1, 136.0,

134.6, 134.5, 134.3, 134.0, 133.7, 129.8, 129.8, 129.7, 129.6, 127.7,

127.7, 127.7, 127.6, 97.6, 71.1, 64.0, 27.2, 27.2, 19.6, 19.3. HRMS

(ESI) m/z: [M + Na] calcd for C H O Si Na 673.3145, found

9.2, 1.7 Hz, 1H), 2.24 (td, J = 12.3, 3.6 Hz, 1H), 1.61 (dd, J = 12.2,

673.3145. [α] = −76 (c 0.2, CHCl ).

.6 Hz, 1H), 1.03−0.93 (m, 24H), 0.81−0.79 (m, 4H). C{ H}

Propargyl 3,4-Bis(O-tert-butyldiphenylsilyl)-2-deoxy-β-D-arabi-

noside (7b). The general procedure was followed by adding glycosyl

donor 4d (50 mg, 0.08 mmol, 1 equiv), DMAP hydrochloride catalyst

3a (3 mg, 0.016 mmol, 20 mol %), thiourea 1 (8 mg, 0.016 mmol, 20

mol %), and propargyl alcohol 5e (5 mg, 5 μL, 0.09 mmol, 1.1 equiv)

NMR (101 MHz, CDCl ): δ 166.4, 139.0, 138.8, 138.7, 133.1, 130.5,

29.9, 128.5, 128.5, 128.5, 128.4, 128.3, 127.8, 127.8, 127.7, 127.7,

9.0, 97.8, 79.5, 74.7, 74.7, 73.8, 73.7, 70.0, 70.0, 68.9, 65.9, 65.5,

9.7, 55.7, 30.2, 17.6, 17.6, 17.5, 17.5, 17.4, 17.4, 17.3, 17.2, 13.8,

3.4, 13.3, 12.8. HRMS (ESI) m/z: [M + NH ]

calcd for

at 40 °C for 24 h to obtain product 7b as a colorless liquid. R

: 0.4

C H O Si NH 974.4906, found 974.4921. [α] = +12 (c 0.06,

(15% ethyl acetate in hexane), amount 43 mg, yield 84%. Selectivity

72 12

CHCl₃).

3,4,6-Tri-O-tert-butyldiphenylsilyl-2-deoxy-α,β-D-glucopyrano-

syl)-(1→6)-1,2:3,4-di-O-isopropylidene-α-D-galactopyranoside

6h). The general procedure was followed by adding glycosyl donor

c (50 mg, 0.06 mmol, 1 equiv), DMAP hydrochloride catalyst 3a (2

mg, 0.012 mmol, 20 mol %), thiourea 1 (6 mg, 0.012 mmol, 20 mol

α/β = 7:1. α-Anomer: H NMR (600 MHz, CDCl ): δ 7.71−7.67 (m,

(

4H), 7.65 (d, J = 7.0 Hz, 2H), 7.60 (d, J = 7.6 Hz, 2H), 7.42−7.37

(m, 4H), 7.36−7.32 (m, 4H), 7.29−7.25 (m, 4H), 5.02 (t, J = 3.4 Hz,

(

H), 4.12 (d, J = 9.2 Hz, 1H), 4.02 (s, 2H), 3.80 (s, 1H), 3.49−3.45

(

m, 1H), 3.32 (dd, J = 11.8, 2.1 Hz, 1H), 2.33 (s, 1H), 2.21 (s, 1H),

.44 (dt, J = 13.0, 3.8 Hz, 1H), 1.08 (s, 18H). C{ H} NMR (151

), and glycosyl acceptor 5f (17 mg, 0.07 mmol, 1.1 equiv) at 40 °C

MHz, CDCl ): δ 136.3, 136.2, 136.2, 136.1, 136.1, 136.1, 136.1,

for 24 h to obtain product 6h as a colorless liquid. R : 0.7 (10% ethyl

acetate in hexane), amount 49 mg, yield 73%. Selectivity α/β = 5:1. α-

Anomer: H NMR (400 MHz, CDCl ): δ 7.56 (d, J = 7.2 Hz, 2H),

134.5, 134.2, 134.0, 133.7, 129.8, 129.8, 129.7, 129.7, 129.6, 129.6,

27.7, 127.7, 127.7, 127.6, 96.7, 79.7, 74.0, 70.93, 64.2, 54.3, 27.2,

27.1, 19.5, 19.4. HRMS (ESI) m/z: [M + NH ]

C H O Si NH 666.3435, found 666.3435. [α] = −81 (c 0.3,

CHCl₃).

calcd for

.46 (d, J = 5.4 Hz, 4H), 7.35- 7.17 (m, 20H), 7.09−7.05 (m, 4H),

.46 (d, J = 4.3 Hz, 1H), 4.96 (d, J = 4.5 Hz, 1H), 4.52 (d, J = 7.8 Hz,

H), 4.23 (s, 1H), 4.15 (d, J = 7.7 Hz, 1H), 3.92 (s, 3H), 3.85 (d, J =

.6 Hz, 1H), 3.73 (d, J = 7.1 Hz, 1H), 3.67 (d, J = 16.9 Hz, 2H), 3.58

Octyl 3,4-Bis(O-tert-butyldiphenylsilyl)-2-deoxy-β-D-arabinoside

(7c). The general procedure was followed by adding glycosyl donor

4d (50 mg, 0.08 mmol, 1 equiv), DMAP hydrochloride catalyst 3a (3

mg, 0.016 mmol, 20 mol %), thiourea 1 (8 mg, 0.016 mmol, 20 mol

%), and octyl alcohol 5g (12 mg, 14 μL, 0.09 mmol, 1.1 equiv) at 40

(d, J = 10.4 Hz, 1H), 1.77 (d, J = 6.3 Hz, 1H), 1.55 (d, J = 4.4 Hz,

H), 1.40 (s, 3H), 1.34 (s, 3H), 1.23 (s, 3H), 1.18 (s, 3H), 0.90 (s,

H), 0.82 (s, 9H), 0.75 (s, 9H).₃C{ H} NMR and HRMS value

were matched with reported data.

°C for 24 h to obtain product 7c as a colorless liquid. R : 0.3 (10%

,5-Di-O-benzyl 2-Deoxy-α,β-furanosyl-(1→6)-2,3,4-tri-O-ben-

ethyl acetate in hexane), amount 51 mg, yield 88%. Selectivity α,α-

zyl-α-D-methylglucopyranoside (6i). The general procedure was

followed by adding glycosyl donor 4e (50 mg, 0.16 mmol, 1 equiv),

DMAP hydrochloride catalyst 3a (3 mg, 0.032 mmol, 20 mol %),

thiourea 1 (16 mg, 0.032 mmol, 20 mol %), and glycosyl acceptor 5h

anomer: H NMR (600 MHz, CDCl ): δ 7.73 (d, J = 7.4 Hz, 4H),

7.66 (d, J = 7.9 Hz, 2H), 7.58 (d, J = 7.3 Hz, 2H), 7.43−7.27 (m,

12H), 4.73 (d, J = 3.6 Hz, 1H), 4.10−4.08 (m, 1H), 3.84 (s, 1H),

3.39−3.37 (m, 1H), 3.33−3.30 (m, 2H), 3.04−2.98 (m, 1H), 2.23 (s,

1H), 1.43−1.39 (m, 1H), 1.27−1.17 (m, 5H), 1.15−1.13 (m, 2H),

1.11 (s, 9H), 1.07 (s, 9H), 1.00 (d, J = 12.9 Hz, 2H), 0.91−0.86 (m,

(

82 mg, 0.18 mmol, 1.1 equiv) at 40 °C for 24 h to obtain product 6i

as a colorless liquid. R : 0.3 (20% ethyl acetate in hexane), amount 85

mg, yield 70%. α: β = 1:1. H NMR (600 MHz, CDCl ): δ 7.38−7.23

1H), 0.83 (t, J = 7.2 Hz, 3H), 0.74 (td, J = 7.5, 3.8 Hz, 2H). C{ H}

(m, 50H), 5.21 (dd, J = 5.4, 2.6 Hz, 1H), 4.94 (d, J = 5.4 Hz, 1H),

NMR (151 MHz, CDCl ): δ 136.3, 136.1, 136.1, 136.0, 134.7, 134.4,

.93 (d, J = 3.5 Hz, 1H), 4.91 (d, J = 3.2 Hz, 1H), 4.83−4.80 (m,

H), 4.73−4.71 (m, 2H), 4.67−4.65 (m, 4H), 4.62−4.54 (m, 4H),

.51 (d, J = 3.4 Hz, 1H), 4.49−4.48 (m, 3H), 4.45−4.42 (m, 2H),

.24−4.22 (m, 1H), 4.18 (q, J = 4.3 Hz, 1H), 4.14−4.11 (m, 1H),

.04−4.01 (m, 1H), 4.00−3.97 (m, 3H), 3.94−3.91 (m, 2H), 3.90−

.87 (m, 1H), 3.77 (d, J = 3.0 Hz, 1H), 3.75−3.72 (m, 2H), 3.62 (dd,

134.1, 133.8, 129.7, 129.6, 129.6, 127.7, 127.7, 127.6, 127.6, 98.5,

98.5, 71.2, 63.9, 63.9, 39.7, 39.6, 30.5, 30.4, 29.2, 29.2, 27.3, 27.2,

23.8, 23.7, 23.2, 23.2, 19.6, 19.3, 14.3, 14.3, 11.3. HRMS (ESI) m/z:

[M + Na] calcd for C H O Si Na 745.4084, found 745.4084.

[α] = −7 (c 0.06, CHCl ).

Methyl 2,3,4-Tri-O-benzyl-6-O-(3,4-bis(O-tert-butyldiphenylsilyl)-

2-deoxy-β-D-arabinosyl)-α-D-glucopyranoside (7d). The general

procedure was followed by adding glycosyl donor 4d (50 mg, 0.08

mmol, 1 equiv), DMAP hydrochloride catalyst 3a (3 mg, 0.016 mmol,

20 mol %), thiourea 1 (8 mg, 0.016 mmol, 20 mol %), and glycosyl

acceptor 5b (42 mg, 0.09 mmol, 1.1 equiv) at 40 °C for 24 h to obtain

J = 10.6, 4.6 Hz, 1H), 3.57−3.50 (m, 4H), 3.49−3.45 (m, 2H), 3.33

(

d, J = 1.0 Hz, 6H), 2.21−2.10 (m, 3H), 1.91 (dd, J = 14.6, 3.0 Hz,

H). ¹³C{ H} NMR (151 MHz, CDCl ): δ 138.9, 138.9, 138.8, 138.6,

38.5, 138.5, 138.2, 138.1, 138.1, 138.0, 128.6, 128.5, 128.5, 128.5,

28.4, 128.4, 128.3, 128.3, 128.2, 128.2, 128.0, 127.9, 127.8, 127.8,

27.8, 127.7, 127.7, 127.6, 127.6, 105.0, 104.4, 98.9, 98.7, 82.8, 82.2,

9.8, 79.3, 79.1, 78.8, 76.6, 76.5, 75.7, 74.8, 74.8, 74.7, 73.7, 73.7,

product 7d as a colorless liquid. R : 0.7 (10% ethyl acetate in hexane),

amount 63 mg, yield 75%. Selectivity α,α-anomer: H NMR (400

3.6, 73.4, 73.3, 73.2, 71.7, 71.6, 70.0, 69.8, 68.7, 67.7, 66.0, 55.5,

MHz, CDCl ): δ 7.75−7.12 (m, 35H), 4.99 (d, J = 11.0 Hz, 1H), 4.80

5.3, 39.3, 38.9. HRMS (ESI) m/z: [M + NH ]

calcd for

(d, J = 11.0 Hz, 1H), 4.75 (d, J = 12.4 Hz, 1H), 4.70−4.66 (m, 3H),

4.51 (d, J = 3.5 Hz, 1H), 4.25 (d, J = 11.0 Hz, 1H), 4.09−4.06 (m,

1H), 3.90 (d, J = 9.3 Hz, 1H), 3.86 (s, 1H), 3.64 (d, J = 10.6 Hz, 1H),

C H O NH 778.3955, found 778.3951. [α]_D= +79 (c 0.4,

CHCl₃).

J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry

Note

.53−3.51 (m, 1H), 3.40−3.38 (m, 1H), 3.37−3.33 (m, 3H), 3.27−

Notes

.24 (m, 1H), 3.22 (s, 3H), 2.21 (t, J = 11.3 Hz, 1H), 1.38 (dt, J =

The authors declare no competing ﬁnancial interest.

2.6, 3.4 Hz, 1H), 1.10 (s, 9H), 1.03 (s, 9H). C{ H} NMR (101

MHz, CDCl3): δ 139.3, 138.5, 138.3, 136.3, 136.1, 136.1, 136.0,

ACKNOWLEDGMENTS

34.1, 133.9, 130.0, 129.8, 129.7, 128.6, 128.5, 128.5, 128.2, 128.0,

27.9, 127.8, 127.8, 127.7, 127.7, 127.6, 98.2, 97.9, 82.2, 79.8, 75.7,

5.1, 73.2, 71.1, 69.8, 65.7, 63.6, 55.1, 37.7, 29.9, 27.3, 27.2, 19.6,

■

P.K.K. is thankful to SERB (DST, New Delhi) for ﬁnancial

assistance through CRG/2019/000918. T.G. and A.M. thank

IITG for fellowships.

9.3. HRMS (ESI) m/z: [M + NH ] calcd for C H O Si NH

65 76

074.5372, found 1074.5387. [α]_D= −86 (c 0.08, CHCl ).

Methyl 2,3,4-Tri-O-benzyl-6-O-(3,4-bis(O-tert-butyldiphenylsilyl)-

-deoxy-β-D-arabinosyl)-α-D-galactopyranoside (7e). The general

REFERENCES

■

procedure was followed by adding glycosyl donor 4d (50 mg, 0.08

mmol, 1 equiv), DMAP hydrochloride catalyst 3a (3 mg, 0.016 mmol,

1) (a) Schreiner, P. R. Metal-free organocatalysis through explicit

hydrogen bonding interactions. Chem. Soc. Rev. 2003 , 32 (5), 289 −

96. (b) Takemoto, Y. Recognition and activation by ureas and

0 mol %), thiourea 1 (8 mg, 0.016 mmol, 20 mol %), and glycosyl

acceptor 5h (42 mg, 0.09 mmol, 1.1 equiv) at 40 °C for 24 h to obtain

product 7e as a colorless liquid. R : 0.6 (10% ethyl acetate in hexane),

thioureas: stereoselective reactions using ureas and thioureas as

hydrogen-bonding donors. Org. Biomol. Chem. 2005 , 3 (24), 4299 −

amount 55 mg, yield 65%. Selectivity α,α-anomer: H NMR (600

MHz, CDCl ): δ 7.71−7.69 (m, 4H), 7.62−7.61 (m, 2H), 7.56 (d, J =

4306. (c) Connon, S. J. Organocatalysis mediated by (thio)urea

derivatives. Chem. - Eur. J. 2006 , 12 (21), 5418 −5427. (d) Taylor, M.

S.; Jacobsen, E. N. Asymmetric catalysis by chiral hydrogen-bond

donors. Angew. Chem., Int. Ed. 2006 , 45 (10), 1520 −1543. (e) Doyle,

A. G.; Jacobsen, E. N. Small-molecule H-bond donors in asymmetric

catalysis. Chem. Rev. 2007, 107 (12), 5713 −5743.

(2) Schreiner, P. R.; Wittkopp, A. H-bonding additives act like Lewis

acid catalysts. Org. Lett. 2002, 4 (2), 217−220.

(3) Zhao, C. F.; Chen, S. B.; Seidel, D. Direct Formation of

Oxocarbenium Ions under Weakly Acidic Conditions: Catalytic

Enantioselective Oxa-Pictet-Spengler Reactions. J. Am. Chem. Soc.

2016, 138 (29), 9053−9056.

(4) Zhang, Z. G.; Schreiner, P. R. (Thio)urea organocatalysis - What

can be learnt from anion recognition? Chem. Soc. Rev. 2009, 38 (4),

1187−1198.

.3 Hz, 2H), 7.42−7.27 (m, 18H), 7.25−7.23 (m, 4H), 7.18−7.12

(

m, 5H), 4.87 (d, J = 11.8 Hz, 1H), 4.83 (d, J = 11.3 Hz, 1H), 4.80−

.78 (m, 2H), 4.72 (d, J = 11.7 Hz, 1H), 4.66 (d, J = 12.1 Hz, 1H),

.61 (d, J = 3.6 Hz, 1H), 4.29 (d, J = 11.4 Hz, 1H), 4.02 (d, J = 9.9

Hz, 1H), 3.98 (dd, J = 10.1, 3.6 Hz, 1H), 3.86 (dd, J = 10.0, 2.9 Hz,

H), 3.75−3.74 (m, 1H), 3.64−3.63 (m, 1H), 3.61 (t, J = 6.5 Hz,

H), 3.43 (dd, J = 10.4, 6.4 Hz, 2H), 3.31 (dd, J = 10.3, 6.4 Hz, 1H),

.24 (s, 3H), 3.09 (d, J = 11.9 Hz, 1H), 2.23−2.21 (m, 1H), 1.47 (d, J

12.5 Hz, 1H), 1.09 (s, 9H), 1.05 (s, 9H). C{ H} NMR (151

MHz, CDCl3): δ 139.0, 138.7, 136.3, 136.1, 136.1, 136.0, 134.6,

34.0, 133.7, 129.8, 129.7, 129.6, 128.5, 128.5, 128.3, 128.2, 128.0,

27.9, 127.7, 127.7, 127.6, 127.6, 127.5, 127.5, 98.8, 98.7, 79.3, 76.6,

5.6, 74.8, 73.7, 73.5, 70.9, 69.3, 63.7, 55.3, 37.2, 32.1, 29.9, 27.2,

7.2, 27.1, 19.9, 19.6, 19.4. HRMS (ESI) m/z: [M + NH ] calcd for

C H O Si NH 1074.5372, found 1074.5369. [α] = −27 (c 0.06,

CHCl₃).

(5) Zuend, S. J.; Jacobsen, E. N. Mechanism of Amido-Thiourea

Catalyzed Enantioselective Imine Hydrocyanation: Transition State

Stabilization via Multiple Non-Covalent Interactions. J. Am. Chem.

Soc. 2009, 131 (42), 15358−15374.

ASSOCIATED CONTENT

■

(

6) Murali, M. G.; Vishnumurthy, K. A.; Seethamraju, S.;

sı Supporting Information

Ramamurthy, P. C. Colorimetric anion sensor based on receptor

having indole- and thiourea-binding sites. RSC Adv. 2014, 4 (39),

The Supporting Information is available free of charge at

https://pubs.acs.org/doi/10.1021/acs.joc.0c02473.

Binding by a Urea in Chloroform Solution. Tetrahedron Lett. 1992 , 33

0592−20598.

7) (a) Smith, P. J.; Reddington, M. V.; Wilcox, C. S. Ion-Pair

Experimental procedures, spectroscopic data for all new

compounds, and crystallographic data for the cocrystal

(41), 6085 −6088. (b) Albert, J. S.; Hamilton, A. D. Synthetic Analogs

of the Ristocetin Binding-Site - Neutral, Multidentate Receptors for

Carboxylate Recognition. Tetrahedron Lett. 1993, 34 (46), 7363−

7366. (c) Fan, E.; Vanarman, S. A.; Kincaid, S.; Hamilton, A. D.

Molecular Recognition - Hydrogen-Bonding Receptors That Function

in Highly Competitive Solvents. J. Am. Chem. Soc. 1993, 115 (1),

(3a.1) (PDF)

Accession Codes

CCDC 2036535 contains the supplementary crystallographic

data for this paper. These data can be obtained free of charge

via www.ccdc.cam.ac.uk/data_request/cif, or by emailing

data_request@ccdc.cam.ac.uk, or by contacting The Cam-

bridge Crystallographic Data Centre, 12 Union Road,

Cambridge CB2 1EZ, UK; fax: +44 1223 336033.

(

69−370.

8) Li, H. Y.; Valkenier, H.; Judd, L. W.; Brotherhood, P. R.;

Hussain, S.; Cooper, J. A.; Jurcek, O.; Sparkes, H. A.; Sheppard, D. N.;

Davis, A. P. Efficient, non-toxic anion transport by synthetic carriers

in cells and epithelia. Nat. Chem. 2016, 8 (1), 24−32.

(9) Balmond, E. I.; Coe, D. M.; Galan, M. C.; McGarrigle, E. M.

AUTHOR INFORMATION

alpha-Selective Organocatalytic Synthesis of 2-Deoxygalactosides.

■

Angew. Chem., Int. Ed. 2012, 51 (36), 9152−9155.

Corresponding Author

(10) Geng, Y. Q.; Kumar, A.; Faidallah, H. M.; Albar, H. A.;

Pavan K. Kancharla − Department of Chemistry, Indian

Institute of Technology Guwahati, Guwahati 781039, Assam,

India; orcid.org/0000-0001-8604-380X;

Email: pavankancharla@iitg.ac.in

Mhkalid, I. A.; Schmidt, R. R. Cooperative Catalysis in Glycosidation

Reactions with O-Glycosyl Trichloroacetimidates as Glycosyl Donors.

Angew. Chem., Int. Ed. 2013, 52 (38), 10089−10092.

(11) (a) Palo-Nieto, C.; Sau, A.; Williams, R.; Galan, M. C.

Cooperative Bronsted Acid-Type Organocatalysis for the Stereo-

selective Synthesis of Deoxyglycosides. J. Org. Chem. 2017, 82 (1),

407−414. (b) Kobayashi, Y.; Nakatsuji, Y.; Li, S. J.; Tsuzuki, S.;

Takemoto, Y. Direct N-Glycofunctionalization of Amides with

Glycosyl Trichloroacetimidate by Thiourea/Halogen Bond Donor

Co-Catalysis. Angew. Chem., Int. Ed. 2018, 57 (14), 3646 −3650.

Authors

Titli Ghosh − Department of Chemistry, Indian Institute of

Technology Guwahati, Guwahati 781039, Assam, India

Ananya Mukherji − Department of Chemistry, Indian Institute

of Technology Guwahati, Guwahati 781039, Assam, India

(12) Sun, L. F.; Wu, X. W.; Xiong, D. C.; Ye, X. S. Stereoselective

Complete contact information is available at:

https://pubs.acs.org/10.1021/acs.joc.0c02473

Koenigs-Knorr Glycosylation Catalyzed by Urea. Angew. Chem., Int.

Ed. 2016, 55 (28), 8041−8044.

J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry

Note

13) Mayfield, A. B.; Metternich, J. B.; Trotta, A. H.; Jacobsen, E. N.

catalysts: The Privileged 3,5-Bis(trifluoromethyl)phenyl Group. Eur. J.

Org. Chem. 2012, 2012 (30), 5919−5927.

Stereospecific Furanosylations Catalyzed by Bis-thiourea Hydrogen-

Bond Donors. J. Am. Chem. Soc. 2020, 142 (8), 4061−4069.

(

Kirm, H.-U.; Abboud, K. A.; Leito, I.; Seidel, D. Modular Design of

Chiral Conjugate-Base-Stabilized Carboxylic Acids: Catalytic Enan-

tioselective [4 + 2] Cycloadditions of Acetals. J. Am. Chem. Soc. 2020,

(28) Yu, F.; Li, J. Y.; DeMent, P. M.; Tu, Y. J.; Schlegel, H. B.;

Nguyen, H. M. Phenanthroline-Catalyzed Stereoretentive Glycosyla-

tions. Angew. Chem., Int. Ed. 2019, 58 (21), 6957−6961.

(29) Strukil, V.; Igrc, M. D.; Eckert-Maksic, M.; Friscic, T. Click

Mechanochemistry: Quantitative Synthesis of ″Ready to Use ″ Chiral

Organocatalysts by Efficient Two-Fold Thiourea Coupling to Vicinal

Diamines. Chem. - Eur. J. 2012, 18 (27), 8464−8473.

14) (a) Zhu, Z.; Odagi, M.; Supantanapong, N.; Xu, W.; Saame, J.;

142 (36), 15252−15258. (b) Odagi, M.; Araki, H.; Min, C.;

Yamamoto, E.; Emge, T. J.; Yamanaka, M.; Seidel, D. Insightsinto

the Structure and Function of a Chiral Conjugate-Base-Stabilized

Brønsted Acid Catalyst. E. J. Org. Chem. 2019, 2019 , 486 −492.

30) Ghosh, T.; Mukherji, A.; Kancharla, P. K. Sterically Hindered

2,4,6-Tri-tent-butylpyridinium Salts as Single Hydrogen Bond Donors

for Highly Stereoselective Glycosylation Reactions of Glycals. Org.

Lett. 2019, 21 (10), 3490−3495.

c) Weil, T.; Kotke, M.; Kleiner, C. M.; Schreiner, P. R. Cooperative

Brønsted Acid-Type Organocatalysis: Alcoholysis of Styrene Oxides.

Org. Lett. 2008, 10 (8), 1513−1516.

(15) Shinde, S.; Incel, A.; Mansour, M.; Olsson, G. D.; Nicholls, I.

A.; Esen, C.; Urraca, J.; Sellergren, B. Urea-Based Imprinted Polymer

Hosts with Switchable Anion Preference. J. Am. Chem. Soc. 2020, 142

(

26), 11404−11416.

16) Brak, K.; Jacobsen, E. N. Asymmetric Ion-Pairing Catalysis.

Angew. Chem., Int. Ed. 2013, 52 (2), 534 −561.

17) Bennett, C. S.; Galan, M. C. Methods for 2-Deoxyglycoside

Synthesis. Chem. Rev. 2018, 118 (17), 7931−7985.

18) Tanaka, H.; Yoshizawa, A.; Takahashi, T. Direct and

(

stereoselective synthesis of beta-linked 2,6-deoxyoligosaccharides.

Angew. Chem., Int. Ed. 2007, 46 (14), 2505−2507.

(19) Nakanishi, M.; Takahashi, D.; Toshima, K. Light-induced O-

glycosylation of unprotected deoxythioglycosyl donors. Org. Biomol.

Chem. 2013, 11 (31), 5079−5082.

(20) (a) Lam, S. N.; Gervay-Hague, J. Efficient route to 2-deoxy

beta-O-aryl-D-glycosides via direct displacement of glycosyl iodides.

Org. Lett. 2003 , 5 (22), 4219 −4222. (b) Thiem, J.; Kopper, S.

Synthesis of Cardiac-Glycosides - Evatromonoside and Its Anomer.

Angew. Chem., Int. Ed. Engl. 1982 , 21 (10), 779 −780.

(21) Kotke, M.; Schreiner, P. R. Generally applicable organocatalytic

tetrahydropyranylation of hydroxy functionalities with very low

catalyst loading. Synthesis 2007, 2007 (5), 779−790.

22) (a) Nogueira, J. M.; Nguyen, S. H.; Bennett, C. S.

Cyclopropenium Cation Promoted Dehydrative Glycosylations

Using 2-Deoxy- and 2,6-Dideoxy-Sugar Donors. Org. Lett. 2011, 13

11), 2814 −2817. (b) Issa, J. P.; Lloyd, D.; Steliotes, E.; Bennett, C.

S. Reagent Controlled beta-Specific Dehydrative Glycosylation

Reactions with 2-Deoxy-Sugars. Org. Lett. 2013 , 15 (16), 4170 −

4173. (c) Issa, J. P.; Bennett, C. S. A Reagent-Controlled S(N)2-

Glycosylation for the Direct Synthesis of beta-Linked 2-Deoxy-Sugars.

J. Am. Chem. Soc. 2014, 136 (15), 5740−5744.

(23) Park, Y.; Harper, K. C.; Kuhl, N.; Kwan, E. E.; Liu, R. Y.;

Jacobsen, E. N. Macrocyclic bis-thioureas catalyze stereospecific

glycosylation reactions. Science 2017, 355 (6321), 162−166.

(24) Ghosh, T.; Mukherji, A.; Srivastava, H. K.; Kancharla, P. K.

Secondary amine salt catalyzed controlled activation of 2-deoxy sugar

lactols towards alpha-selective dehydrative glycosylation. Org. Biomol.

Chem. 2018, 16 (16), 2870−2875.

(b) Bryant, G. L., Jr.; King, J. A., Jr. Structures of 2 Acylpyridinium

25) (a) Chao, M.; Schempp, E.; Rosenstein, R. D. 4-

Dimethylaminopyridine Hydrochloride Dihydrate. Acta Crystallogr.,

Sect. B: Struct. Crystallogr. Cryst. Chem. 1977 , 33 (Jun15), 1820 −1823.

Salts and One Simple Pyridinium Salt. Acta Crystallogr., Sect. C: Cryst.

Struct. Commun. 1992 , 48 , 2036 −2039. (c) Liu, Z. H.; Ma, Q. Q.; Liu,

Y. X.; Wang, Q. M. 4-(N,N-Dimethylamino)pyridine Hydrochloride

as a Recyclable Catalyst for Acylation of Inert Alcohols: Substrate

Scope and Reaction Mechanism. Org. Lett. 2014, 16 (1), 236−239.

(26) Juste-Navarro, V.; Prieto, L.; Delso, I.; Manzano, R.; Tejero, T.;

Reyes, E.; Vicario, J. L.; Merino, P. A Case Study of Thiourea-Assisted

Iminium Formation by Hydroxyl Anion Binding: Kinetic, Spectro-

scopic and Computational Evidences. Adv. Synth. Catal. 2017, 359

(

23), 4122−4128.

27) Lippert, K. M.; Hof, K.; Gerbig, D.; Ley, D.; Hausmann, H.;

Guenther, S.; Schreiner, P. R. Hydrogen-Bonding Thiourea Organo-

(