- Email: [email protected]
Methoxyacetic acid esters: Applications in protecting group and glycosylation chemistry
Journal Pre-proof Methoxyacetic acid esters: Applications in protecting group and glycosylation chemistry Spencer J. Williams PII:
S0008-6215(19)30549-X
DOI:
https://doi.org/10.1016/j.carres.2019.107848
Reference:
CAR 107848
To appear in:
Carbohydrate Research
Received Date: 13 September 2019 Revised Date:
16 October 2019
Accepted Date: 17 October 2019
Please cite this article as: S.J. Williams, Methoxyacetic acid esters: Applications in protecting group and glycosylation chemistry, Carbohydrate Research (2019), doi: https://doi.org/10.1016/ j.carres.2019.107848. This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. © 2019 Published by Elsevier Ltd.
Graphical abstract:
1
Methoxyacetic acid esters: Applications in protecting group and glycosylation chemistry
2
Spencer J. Williams
3
School of Chemistry and Bio21 Molecular Science and Biotechnology Institute, University of
4
Melbourne, Parkville, Victoria, Australia 3010
5
E-mail: [email protected]
6 7 8
Abstract:
9
The methoxyacetate (MAc) protecting group was introduced over 50 years ago and has proved useful
10
owing to its combination of stability and its ability to be selectively removed in the presence of
11
unactivated esters and a wide variety of other protecting groups. Glycosyl methoxyacetates have been
12
investigated as glycosyl donors under activation by lanthanoids. In this mini-review we highlight a
13
range of useful transformations enabled by judicious application of the methoxyacetate group.
14 15 16
1
17
Introduction: Methoxyacetate (MAc) esters were developed by Reese and Stewart as a protecting
18
group that can be removed in the presence of acetate and benzoate groups for use in nucleoside
19
chemistry [1]. Their stability and capacity to be selectively removed in the presence of assorted ester
20
groups under mildly selective conditions has led to their use as protecting groups in natural product
21
and carbohydrate chemistry, especially for targets that contain native ester groups. In addition,
22
glycosyl methoxyacetates have been developed as glycosyl donors under promotion by lanthanide
23
Lewis acids.
24
Installation of the methoxyacetate group: The main reagents used for the introduction of MAc
25
esters are the commercially available methoxyacetic anhydride (MAc2O) and methoxyacetyl chloride
26
(MAcCl) [2] (Table 1), or the easily prepared N-hydroxysuccinimidyl methoxyacetate (NHS-MAc)
27
[3]. The combinations MAc2O/iPr2NEt [4], MAc2O/pyr [5-7], MAc2O/DMAP/pyr [8] and
28
MAcCl/pyridine [9, 10] are most commonly used for formation of MAc esters. In an attempted
29
chemoselective acylation of taxol, N-hydroxysuccinimidyl-MAc/iPr2NEt was superior to MAcCl for
30
selective acylation of a primary over secondary alcohol [3]. Primary MAc esters have been introduced
31
by nucleophilic substitution of primary tosylates (e.g. 1→2) using tetraethylammonium
32
methoxyacetate in acetonitrile; the lower nucleophilicity of the MAc anion required longer reaction
33
times than for the corresponding acetate (Scheme 1a) [11]. MAcOH/Yb(OTf)3 can catalyse the
34
esterification of simple alcohols [12].
35
Table 1. Methoxyacetic acid and related reagents CAS number
MW
b.p °C (density g/mL at 25 °C)
(g/mol) Methoxyacetic acid
625-45-6
90.08
202-204 (d 1.174)
38870-89-2
108.52
112-113 (d 1.187)
19500-95-9
162.14
74-77 @ 2 mmHg (d 1.19)
(MAcOH) Methoxyacetyl chloride (MAcCl) Methoxyacetic anhydride (MAc2O) 36
2
37 38
Scheme 1. Examples showing the installation and removal of methoxyacetyl groups.
39 40
Stability of methoxyacetates: The pKa value of methoxyacetic acid is 3.53, which resides midway
41
between that of acetic acid (4.76) and chloroacetic acid (2.81); thus the methoxyacetate group can be
42
considered to have a reactivity that falls between acetates and chloroacetates [1]. Methoxyacetates
43
were highlighted as superior to chloroacetates in their stability to hydrolysis in the context of a taxol
44
derivative [3], and were selected in preference to acetates owing to their comparative ease of cleavage,
45
preventing an unwanted β-elimination elsewhere in a complex advanced spongistatin 2 intermediate
46
[4]. Methoxyacetates are stable to a wide range of non-nucleophilic conditions but are sensitive to
47
extended treatment with mild nucleophiles. Attempts to conduct the Sharpless asymmetric
48
dihydroxylation of allyl tetra-O-methoxyacetyl-α-D-glucopyranoside in a t-BuOH/H2O solvent system
49
failed owing to hydrolysis of MAc groups [10]. However, Jacobsen hydrolytic kinetic resolution
50
applied to the epoxide derived from the same substrate was successful, showing that low amounts of
51
water may be tolerated [10]. MAc groups are stable to the conditions of NIS/TfOH (9 + 10 → 11), and
52
can withstand conditions used to remove levulinoyl esters (8 → 9; Scheme 2).[7]
3
53 54
Scheme 2. Utility of MAc groups in pseudonucleotide synthesis.
55 56
Cleavage of methoxyacetates: The most commonly applied methods for cleavage of MAc groups
57
involve nucleophilic conditions such as NH3/MeOH [5], aq NaOH/dioxane [6],
58
KOtBu/MeOH/CH2Cl2 [7] or other primary or secondary amines. In methanolic ammonia, the
59
cleavage of a primary methoxyacetate was 24-fold faster than the corresponding acetate; in aqueous
60
ammonia the rate was 18-fold faster [1]. Ethanolamine/2-propanol or CHCl3 was effective for
61
cleavage of a single MAc group in the preparation of various taxol-derived carbamates, maintaining
62
the sensitive C13-side-chain as well as acetate and benzoate groups (13 → 14; Scheme 3a) [3]. A
63
solitary MAc group was cleaved using imidazole/2-propanol in the context of a complex taxol-derived
64
polyester [3]. An alternative solution to a similar challenge in the context of C2-modified taxol
65
analogues was met through the use of MeOH and ZnI2 (10 equiv) [13]. Aminolysis of MAc groups in
66
15 could be accomplished with morpholine/THF coincident with formation of
67
phosphorodithioamidate 16 (Scheme 3b) [6]. NH3/MeOH provided selective cleavage of a single MAc
68
group in the advanced spongistatin intermediate 17, without cleavage of the acetate or β-elimination
69
(Scheme 3c) [4]. In the synthesis of bryostatin 2, good selectivity for removal of a single MAc group
70
over benzoate and acetate groups in 19 was obtained with Na2CO3/MeOH (Scheme 3d) [8].
4
a)
O AcO
BzHN
O
O
Ph
O
O
O
13
MAcO
then HOCH2CH2NH2 reflux, 21 h 50%
O
H
HO
OBz AcO
13
AcO
PEG-NH2, 2-propanol reflux, 21 h
N
BzHN
O
O
Ph
O
PEG O
OH
N Et3NH
S
P
O
O
N
O
S
N
NHPx N
N
N
MAcO
OMAc
Et3NH
morpholine, THF
N
S N
rt, 16 h, 97%
15 N
O
H OBz AcO
HO
14 NHPx
b)
NH
P
O O
S
N
N
N
O
16 HO
Px = 9-phenylxanthen-9-yl
OH
OTBS
c) TESO H
d)
O OMe H
O
MeO2C
O OTES TBSO
MeO
OMe
O
O
O
O
RO
OMe H OTES O O
O O
OPMB
O RO
AcO
OPMB
OAc CO2Me OTES NH3, MeOH 82%
71
17 R = MAc 18 R = H
Na2CO3, MeOH 82%
19 R = MAc 20 R = H
72
Scheme 3. Examples showing the removal of methoxyacetyl groups in the context of complex natural
73
products.
74
t-BuNH2/MeOH/CHCl3 allowed selective removal of a single MAc group in the presence of a
75
fatty acid ester (2 → 3; Scheme 1a) [11]. In a more discriminating example, the t-
76
BuNH2/MeOH/CHCl3 system enabled the selective cleavage of four MAc groups in the presence of
77
two fatty acid esters (4 → 5; Scheme 1b) [10, 14]. NaBH4/EtOH is effective for the cleavage of MAc
78
groups relative to tert-butyl esters, N-Boc, N-Fmoc, N-Cbz, N-acetyl, N-MAc, N-benzyl, O-benzyl, O-
79
acetyl, and O-TBDMS, and can be used for the cleavage of S-MAc groups [15].
80
Yb(OTf)3 catalyses the methanolysis of MAc esters in the presence of acetyl, benzoyl, benzyl,
81
isopropylidene, THP, TBDMS, TBDPS, and MEM groups (e.g. 6 → 7; Scheme 1c) [12]. However,
82
Yb(OTf)3/MeOH was described as inferior to t-BuNH2/MeOH/CHCl3 for selective cleavage of a MAc
83
group in the presence of a fatty acid ester [12]. 5
84
A racemic 4-methoxyacetoxypentanenitrile was a substrate for lipase PS (from Pseudomonas
85
sp.), allowing kinetic resolution of the corresponding alcohol with modest enantiomeric excess [16].
86
Glycosylation reactions: Glycosyl methoxyacetates (e.g. 21) can be activated as glycosyl donors
87
with stoichiometric Zn2+ salts [17] or catalytic amounts of a variety of lanthanide salts (Tb(OTf)3,
88
Ho(OTf)3, Tm(OTf)3 and Yb(OTf)3) (Figure 1a) [18], whereas the corresponding glycosyl acetates are
89
inert. Among the lanthanides that were effective, Yb(OTf)3 was highlighted as a cost-effective salt;
90
the glycosylation reaction was optimized to use 1-30 mol% of the salt in acetonitrile at 53 °C.
91
Glycosylation reactions were successful for a range of primary and secondary alcohols, and thiols,
92
affording the corresponding (thio)glycosides in mostly good yields. A ribofuranosyl donor reacted
93
with good β-selectivity [18]. Yb(OTf)3/MAcOH can be used for activation of sugar hemiacetals (e.g. 22) to glycosylate a
94 95
range of primary and secondary alcohols and thiols to afford the (thio)glycosides (Figure 1b) [19]. The
96
reaction involves catalysis of both the esterification of the sugar as well as the activation of the
97
intermediate glycosyl methoxyacetate [17]. Yields were highest when the reaction was refluxed below
98
a column of activated molecular sieves to remove water [19]. a) Yb(OTf) 3-catalyzed glycosylation using glycosyl methoxyacetates BnO
O
BnO
Yb(OTf) 3 (1-30 mol%)
O
BnO BnO
BnO BnO
OMe
O
MeCN, 53 °C
BnO
HS
HO
O O
O
OR BnO
21 HO
O
BnO BnO
O
O BnO
O
87%, : 27:73
n-C8H17OH
n-C8H17SH
99%, : 36:64
99%, : 58:42
OMe
94%, : 30:70
97%, : 55:45
b) Yb(OTf) 3/MAcOH-catalyzed glycosylation using sugar hemiacetals MAcOH (10-30 mol%) Yb(OTf) 3 (10-30 mol%)
BnO O
BnO BnO
OH
22 O
OH O
O OO
99
85%, : 48:52
BnO
BnO O
BnO BnO
OR BnO
1,2-DCE, 53 °C [* CH2Cl2/ reflux was used] O
HO BnO BnO
O O BnO
O OMe
99%,* : 75:25
HS
HO
O OH
Br
O
81%, : 40:60
72%,* : 82:18
99%,* : 63:37
6
100
Figure 1. Yb(OTf)3-catalyzed glycosylation using (a) glycosyl methoxyacetates as glycosyl donors
101
[18] and (b) sugar hemiacetals and catalytic methoxyacetic acid (via glycosyl methoxyacetates) [19].
102
Acknowledgement
103
The Australian Research Council (DP180101957).
104
References
105 106 107 108 109 110 111 112 113 114 115 116 117 118 119 120 121 122 123 124 125 126 127
[1] C.B. Reese, J.C.M. Stewart, Tetrahedron Lett., 9 (1968) 4273-4276. [2] J. Stadlwieser, Synthesis, (1985) 490. [3] R.B. Greenwald, A. Pendri, D. Bolikal, J. Org. Chem., 60 (1995) 331-336. [4] D.A. Evans, B.W. Trotter, B. Côté, P.J. Coleman, L.C. Dias, A.N. Tyler, Angew. Chem. Int. Ed., 36 (1997) 27442747. [5] C.B. Reese, P.A. Skone, J. Chem. Soc., Perkin Trans. 1, (1984) 1263-1271. [6] C.B. Reese, L.H.K. Shek, Z. Zhao, J. Chem. Soc., Perkin Trans. 1, (1995) 3077-3084. [7] G.H. Veeneman, G.A. Van Der Marel, H. Van Den Elst, J.H. Van Boom, Tetrahedron, 47 (1991) 1547-1562. [8] D.A. Evans, P.H. Carter, E.M. Carreira, A.B. Charette, J.A. Prunet, M. Lautens, J. Am. Chem. Soc., 121 (1999) 7540-7552. [9] S.D. Burke, W.F. Fobare, G.J. Pacofsky, J. Org. Chem., 48 (1983) 5221-5228. [10] S. Shah, M. Nagata, S. Yamasaki, S.J. Williams, Chem. Commun., 52 (2016) 10902-10905. [11] R. Rosseto, N. Bibak, R. DeOcampo, T. Shah, A. Gabrielian, J. Hajdu, J. Org. Chem., 72 (2007) 1691-1698. [12] T. Hanamoto, Y. Sugimoto, Y. Yokoyama, J. Inanaga, J. Org. Chem., 61 (1996) 4491-4492. [13] J.-P. Pulicani, D. Bézard, J.-D. Bourzat, H. Bouchard, M. Zucco, D. Deprez, A. Commerçon, Tetrahedron Lett., 35 (1994) 9717-9720. [14] M.B. Richardson, D.G. Smith, S.J. Williams, Chem. Commun., 53 (2017) 1100-1103. [15] P.K. Gadekar, M. Hoermann, F. Corbo, R. Sharma, S. Sarveswari, A. Roychowdhury, Tetrahedron Lett., 55 (2014) 503-506. [16] Y. Takagi, T. Itoh, Bull. Soc. Chim. Jpn., 66 (1993) 2949-2953. [17] Y. Yokoyama, T. Hanamoto, S. Suzuki, K. Shimizu, H. Furuno, J. Inanaga, Heterocycles, 79 (2009) 967-983. [18] J. Inanaga, Y. Yokoyama, T. Hanamoto, Tetrahedron Lett., 34 (1993) 2791-2794. [19] J. Inanaga, Y. Yokoyama, T. Hanamoto, J. Chem. Soc., Chem. Commun., (1993) 1090-1091.
128
7
Highlights: • Methoxyacetates are a useful ester protecting group for applications in complex total synthesis and carbohydrate chemistry, particularly targets involving native ester groups • Methoxyacetates can be removed selectively in the presence of a wide range of esters and other functional groups •
Glycosyl methoxyacetates act as glycosyl donors under lanthanoid activation
Declaration of interests ☒ The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. ☐The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:
S0008-6215(19)30549-X
DOI:
https://doi.org/10.1016/j.carres.2019.107848
Reference:
CAR 107848
To appear in:
Carbohydrate Research
Received Date: 13 September 2019 Revised Date:
16 October 2019
Accepted Date: 17 October 2019
Please cite this article as: S.J. Williams, Methoxyacetic acid esters: Applications in protecting group and glycosylation chemistry, Carbohydrate Research (2019), doi: https://doi.org/10.1016/ j.carres.2019.107848. This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. © 2019 Published by Elsevier Ltd.
Graphical abstract:
1
Methoxyacetic acid esters: Applications in protecting group and glycosylation chemistry
2
Spencer J. Williams
3
School of Chemistry and Bio21 Molecular Science and Biotechnology Institute, University of
4
Melbourne, Parkville, Victoria, Australia 3010
5
E-mail: [email protected]
6 7 8
Abstract:
9
The methoxyacetate (MAc) protecting group was introduced over 50 years ago and has proved useful
10
owing to its combination of stability and its ability to be selectively removed in the presence of
11
unactivated esters and a wide variety of other protecting groups. Glycosyl methoxyacetates have been
12
investigated as glycosyl donors under activation by lanthanoids. In this mini-review we highlight a
13
range of useful transformations enabled by judicious application of the methoxyacetate group.
14 15 16
1
17
Introduction: Methoxyacetate (MAc) esters were developed by Reese and Stewart as a protecting
18
group that can be removed in the presence of acetate and benzoate groups for use in nucleoside
19
chemistry [1]. Their stability and capacity to be selectively removed in the presence of assorted ester
20
groups under mildly selective conditions has led to their use as protecting groups in natural product
21
and carbohydrate chemistry, especially for targets that contain native ester groups. In addition,
22
glycosyl methoxyacetates have been developed as glycosyl donors under promotion by lanthanide
23
Lewis acids.
24
Installation of the methoxyacetate group: The main reagents used for the introduction of MAc
25
esters are the commercially available methoxyacetic anhydride (MAc2O) and methoxyacetyl chloride
26
(MAcCl) [2] (Table 1), or the easily prepared N-hydroxysuccinimidyl methoxyacetate (NHS-MAc)
27
[3]. The combinations MAc2O/iPr2NEt [4], MAc2O/pyr [5-7], MAc2O/DMAP/pyr [8] and
28
MAcCl/pyridine [9, 10] are most commonly used for formation of MAc esters. In an attempted
29
chemoselective acylation of taxol, N-hydroxysuccinimidyl-MAc/iPr2NEt was superior to MAcCl for
30
selective acylation of a primary over secondary alcohol [3]. Primary MAc esters have been introduced
31
by nucleophilic substitution of primary tosylates (e.g. 1→2) using tetraethylammonium
32
methoxyacetate in acetonitrile; the lower nucleophilicity of the MAc anion required longer reaction
33
times than for the corresponding acetate (Scheme 1a) [11]. MAcOH/Yb(OTf)3 can catalyse the
34
esterification of simple alcohols [12].
35
Table 1. Methoxyacetic acid and related reagents CAS number
MW
b.p °C (density g/mL at 25 °C)
(g/mol) Methoxyacetic acid
625-45-6
90.08
202-204 (d 1.174)
38870-89-2
108.52
112-113 (d 1.187)
19500-95-9
162.14
74-77 @ 2 mmHg (d 1.19)
(MAcOH) Methoxyacetyl chloride (MAcCl) Methoxyacetic anhydride (MAc2O) 36
2
37 38
Scheme 1. Examples showing the installation and removal of methoxyacetyl groups.
39 40
Stability of methoxyacetates: The pKa value of methoxyacetic acid is 3.53, which resides midway
41
between that of acetic acid (4.76) and chloroacetic acid (2.81); thus the methoxyacetate group can be
42
considered to have a reactivity that falls between acetates and chloroacetates [1]. Methoxyacetates
43
were highlighted as superior to chloroacetates in their stability to hydrolysis in the context of a taxol
44
derivative [3], and were selected in preference to acetates owing to their comparative ease of cleavage,
45
preventing an unwanted β-elimination elsewhere in a complex advanced spongistatin 2 intermediate
46
[4]. Methoxyacetates are stable to a wide range of non-nucleophilic conditions but are sensitive to
47
extended treatment with mild nucleophiles. Attempts to conduct the Sharpless asymmetric
48
dihydroxylation of allyl tetra-O-methoxyacetyl-α-D-glucopyranoside in a t-BuOH/H2O solvent system
49
failed owing to hydrolysis of MAc groups [10]. However, Jacobsen hydrolytic kinetic resolution
50
applied to the epoxide derived from the same substrate was successful, showing that low amounts of
51
water may be tolerated [10]. MAc groups are stable to the conditions of NIS/TfOH (9 + 10 → 11), and
52
can withstand conditions used to remove levulinoyl esters (8 → 9; Scheme 2).[7]
3
53 54
Scheme 2. Utility of MAc groups in pseudonucleotide synthesis.
55 56
Cleavage of methoxyacetates: The most commonly applied methods for cleavage of MAc groups
57
involve nucleophilic conditions such as NH3/MeOH [5], aq NaOH/dioxane [6],
58
KOtBu/MeOH/CH2Cl2 [7] or other primary or secondary amines. In methanolic ammonia, the
59
cleavage of a primary methoxyacetate was 24-fold faster than the corresponding acetate; in aqueous
60
ammonia the rate was 18-fold faster [1]. Ethanolamine/2-propanol or CHCl3 was effective for
61
cleavage of a single MAc group in the preparation of various taxol-derived carbamates, maintaining
62
the sensitive C13-side-chain as well as acetate and benzoate groups (13 → 14; Scheme 3a) [3]. A
63
solitary MAc group was cleaved using imidazole/2-propanol in the context of a complex taxol-derived
64
polyester [3]. An alternative solution to a similar challenge in the context of C2-modified taxol
65
analogues was met through the use of MeOH and ZnI2 (10 equiv) [13]. Aminolysis of MAc groups in
66
15 could be accomplished with morpholine/THF coincident with formation of
67
phosphorodithioamidate 16 (Scheme 3b) [6]. NH3/MeOH provided selective cleavage of a single MAc
68
group in the advanced spongistatin intermediate 17, without cleavage of the acetate or β-elimination
69
(Scheme 3c) [4]. In the synthesis of bryostatin 2, good selectivity for removal of a single MAc group
70
over benzoate and acetate groups in 19 was obtained with Na2CO3/MeOH (Scheme 3d) [8].
4
a)
O AcO
BzHN
O
O
Ph
O
O
O
13
MAcO
then HOCH2CH2NH2 reflux, 21 h 50%
O
H
HO
OBz AcO
13
AcO
PEG-NH2, 2-propanol reflux, 21 h
N
BzHN
O
O
Ph
O
PEG O
OH
N Et3NH
S
P
O
O
N
O
S
N
NHPx N
N
N
MAcO
OMAc
Et3NH
morpholine, THF
N
S N
rt, 16 h, 97%
15 N
O
H OBz AcO
HO
14 NHPx
b)
NH
P
O O
S
N
N
N
O
16 HO
Px = 9-phenylxanthen-9-yl
OH
OTBS
c) TESO H
d)
O OMe H
O
MeO2C
O OTES TBSO
MeO
OMe
O
O
O
O
RO
OMe H OTES O O
O O
OPMB
O RO
AcO
OPMB
OAc CO2Me OTES NH3, MeOH 82%
71
17 R = MAc 18 R = H
Na2CO3, MeOH 82%
19 R = MAc 20 R = H
72
Scheme 3. Examples showing the removal of methoxyacetyl groups in the context of complex natural
73
products.
74
t-BuNH2/MeOH/CHCl3 allowed selective removal of a single MAc group in the presence of a
75
fatty acid ester (2 → 3; Scheme 1a) [11]. In a more discriminating example, the t-
76
BuNH2/MeOH/CHCl3 system enabled the selective cleavage of four MAc groups in the presence of
77
two fatty acid esters (4 → 5; Scheme 1b) [10, 14]. NaBH4/EtOH is effective for the cleavage of MAc
78
groups relative to tert-butyl esters, N-Boc, N-Fmoc, N-Cbz, N-acetyl, N-MAc, N-benzyl, O-benzyl, O-
79
acetyl, and O-TBDMS, and can be used for the cleavage of S-MAc groups [15].
80
Yb(OTf)3 catalyses the methanolysis of MAc esters in the presence of acetyl, benzoyl, benzyl,
81
isopropylidene, THP, TBDMS, TBDPS, and MEM groups (e.g. 6 → 7; Scheme 1c) [12]. However,
82
Yb(OTf)3/MeOH was described as inferior to t-BuNH2/MeOH/CHCl3 for selective cleavage of a MAc
83
group in the presence of a fatty acid ester [12]. 5
84
A racemic 4-methoxyacetoxypentanenitrile was a substrate for lipase PS (from Pseudomonas
85
sp.), allowing kinetic resolution of the corresponding alcohol with modest enantiomeric excess [16].
86
Glycosylation reactions: Glycosyl methoxyacetates (e.g. 21) can be activated as glycosyl donors
87
with stoichiometric Zn2+ salts [17] or catalytic amounts of a variety of lanthanide salts (Tb(OTf)3,
88
Ho(OTf)3, Tm(OTf)3 and Yb(OTf)3) (Figure 1a) [18], whereas the corresponding glycosyl acetates are
89
inert. Among the lanthanides that were effective, Yb(OTf)3 was highlighted as a cost-effective salt;
90
the glycosylation reaction was optimized to use 1-30 mol% of the salt in acetonitrile at 53 °C.
91
Glycosylation reactions were successful for a range of primary and secondary alcohols, and thiols,
92
affording the corresponding (thio)glycosides in mostly good yields. A ribofuranosyl donor reacted
93
with good β-selectivity [18]. Yb(OTf)3/MAcOH can be used for activation of sugar hemiacetals (e.g. 22) to glycosylate a
94 95
range of primary and secondary alcohols and thiols to afford the (thio)glycosides (Figure 1b) [19]. The
96
reaction involves catalysis of both the esterification of the sugar as well as the activation of the
97
intermediate glycosyl methoxyacetate [17]. Yields were highest when the reaction was refluxed below
98
a column of activated molecular sieves to remove water [19]. a) Yb(OTf) 3-catalyzed glycosylation using glycosyl methoxyacetates BnO
O
BnO
Yb(OTf) 3 (1-30 mol%)
O
BnO BnO
BnO BnO
OMe
O
MeCN, 53 °C
BnO
HS
HO
O O
O
OR BnO
21 HO
O
BnO BnO
O
O BnO
O
87%, : 27:73
n-C8H17OH
n-C8H17SH
99%, : 36:64
99%, : 58:42
OMe
94%, : 30:70
97%, : 55:45
b) Yb(OTf) 3/MAcOH-catalyzed glycosylation using sugar hemiacetals MAcOH (10-30 mol%) Yb(OTf) 3 (10-30 mol%)
BnO O
BnO BnO
OH
22 O
OH O
O OO
99
85%, : 48:52
BnO
BnO O
BnO BnO
OR BnO
1,2-DCE, 53 °C [* CH2Cl2/ reflux was used] O
HO BnO BnO
O O BnO
O OMe
99%,* : 75:25
HS
HO
O OH
Br
O
81%, : 40:60
72%,* : 82:18
99%,* : 63:37
6
100
Figure 1. Yb(OTf)3-catalyzed glycosylation using (a) glycosyl methoxyacetates as glycosyl donors
101
[18] and (b) sugar hemiacetals and catalytic methoxyacetic acid (via glycosyl methoxyacetates) [19].
102
Acknowledgement
103
The Australian Research Council (DP180101957).
104
References
105 106 107 108 109 110 111 112 113 114 115 116 117 118 119 120 121 122 123 124 125 126 127
[1] C.B. Reese, J.C.M. Stewart, Tetrahedron Lett., 9 (1968) 4273-4276. [2] J. Stadlwieser, Synthesis, (1985) 490. [3] R.B. Greenwald, A. Pendri, D. Bolikal, J. Org. Chem., 60 (1995) 331-336. [4] D.A. Evans, B.W. Trotter, B. Côté, P.J. Coleman, L.C. Dias, A.N. Tyler, Angew. Chem. Int. Ed., 36 (1997) 27442747. [5] C.B. Reese, P.A. Skone, J. Chem. Soc., Perkin Trans. 1, (1984) 1263-1271. [6] C.B. Reese, L.H.K. Shek, Z. Zhao, J. Chem. Soc., Perkin Trans. 1, (1995) 3077-3084. [7] G.H. Veeneman, G.A. Van Der Marel, H. Van Den Elst, J.H. Van Boom, Tetrahedron, 47 (1991) 1547-1562. [8] D.A. Evans, P.H. Carter, E.M. Carreira, A.B. Charette, J.A. Prunet, M. Lautens, J. Am. Chem. Soc., 121 (1999) 7540-7552. [9] S.D. Burke, W.F. Fobare, G.J. Pacofsky, J. Org. Chem., 48 (1983) 5221-5228. [10] S. Shah, M. Nagata, S. Yamasaki, S.J. Williams, Chem. Commun., 52 (2016) 10902-10905. [11] R. Rosseto, N. Bibak, R. DeOcampo, T. Shah, A. Gabrielian, J. Hajdu, J. Org. Chem., 72 (2007) 1691-1698. [12] T. Hanamoto, Y. Sugimoto, Y. Yokoyama, J. Inanaga, J. Org. Chem., 61 (1996) 4491-4492. [13] J.-P. Pulicani, D. Bézard, J.-D. Bourzat, H. Bouchard, M. Zucco, D. Deprez, A. Commerçon, Tetrahedron Lett., 35 (1994) 9717-9720. [14] M.B. Richardson, D.G. Smith, S.J. Williams, Chem. Commun., 53 (2017) 1100-1103. [15] P.K. Gadekar, M. Hoermann, F. Corbo, R. Sharma, S. Sarveswari, A. Roychowdhury, Tetrahedron Lett., 55 (2014) 503-506. [16] Y. Takagi, T. Itoh, Bull. Soc. Chim. Jpn., 66 (1993) 2949-2953. [17] Y. Yokoyama, T. Hanamoto, S. Suzuki, K. Shimizu, H. Furuno, J. Inanaga, Heterocycles, 79 (2009) 967-983. [18] J. Inanaga, Y. Yokoyama, T. Hanamoto, Tetrahedron Lett., 34 (1993) 2791-2794. [19] J. Inanaga, Y. Yokoyama, T. Hanamoto, J. Chem. Soc., Chem. Commun., (1993) 1090-1091.
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7
Highlights: • Methoxyacetates are a useful ester protecting group for applications in complex total synthesis and carbohydrate chemistry, particularly targets involving native ester groups • Methoxyacetates can be removed selectively in the presence of a wide range of esters and other functional groups •
Glycosyl methoxyacetates act as glycosyl donors under lanthanoid activation
Declaration of interests ☒ The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. ☐The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: