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Regioselective Synthesis of Highly Substituted Imidazoles via
a Sequential Reaction of Allenyl Sulfonamides and Amines
Lian Yu, Yuan Deng, and Jian Cao
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.5b00141 • Publication Date (Web): 08 Apr 2015
Downloaded from http://pubs.acs.org on April 12, 2015

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Page 1 of 23 The Journal of Organic Chemistry

1
2
3
4
5
6 Regioselective Synthesis of Highly Substituted Imidazoles via a
7
8
9 Sequential Reaction of Allenyl Sulfonamides and Amines
10
11
12
13
14 Lian Yu, Yuan Deng, and Jian Cao*
15
16 Key Laboratory of Organosilicon Chemistry and Material Technology of Ministry of
17
18
19 Education, Hangzhou Normal University, Wenyi Road 222, Hangzhou 310012,
20
21 People’s Republic of China
22
23
24 caojian@hznu.edu.cn
25
26
27
28 R1 R1
2 R1 EWG 2
29 R EWG R 5
NH2 4
R NH2 R EWG
30 K2CO3, DMF, air R2 N Ts K2CO3, DMF, air
31 N N R4 N N
100 oC or 125 oC 100 oC or 125 oC
32 R5
3
R R3 R3
R3 = alkyl R3 = aryl
33 5 4
R = aryl, vinyl R = alkyl, aryl
34
35
36
37
38 Abstract. A novel synthesis of imidazoles from electron-withdrawing group
39
40 substituted allenyl sulfonamides with amines was developed. The 4- and
41
42
43 5-functionalized imidazoles were constructed regioselectively depending on the
44
45 substituents on the nitrogen atoms.
46
47
48
49
50 Imidazoles are an important class of heterocyclic compounds which are not only a
51
52
53 fundamental motif found in various natural products but also a key structural unit in
54
55 pharmaceutical compounds.1 For example, Olmesartan 1, a kind of angiotensin II
56
57
58 receptor antagonists,2 consists of an imidazole-5-carboxylate unit (Figure 1).
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2
3
4 Imidazole-4-carboxamide compound 2 is discovered to be a potent and highly
5
6 selective CB2 receptor antagonist3 and imidazolo-nectrisine-phosphono acid
7
8
9 derivative 3 is found to be a potential glycosyltranferase inhibitor.4 Recently,
10
11 imidazoles are also used as precursors to environmentally friendly ionic solvents5 and
12
13
14 carbene ligands.6 Thus the synthesis of functionalized imidazoles has attracted
15
16 considerable attention and many methods have been developed for their synthesis.7
17
18
19 However, reported methods can be limited with respect to the types and locations of
20
21 functional group substituents and regioselectivity. Therefore it is still highly desirable
22
23
24 to develop direct and efficient strategies that afford imidazoles derivatives.
25
26
27 O
28 O O
29 HO O
O
30
31 N N
32 N
33 NH
N N
34 1 Olmesartan
35
36
37 O
O
38 HO
P O
NH
39 HO
40 N
Ph N N
41 HO N
42
43 2 HO 3
44
45 Figure 1. Several imidazole derivatives reported as biologically active compounds and
46
47 pharmaceutical products.
48
49 Allenamides and ynamides, special classes of functionalized allenes and alkynes,
50
51
52
have recently received much attention in the synthetic community.8,9 Various
53
54 nitrogen-containing building blocks including nitrogen heterocycles were successfully
55
56
57
synthesized from allenamides and ynamides.10,11 Recently, Rabasso and co-workers
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2
3
4 reported a simple and efficient synthesis of α-amino allenephosphonates by the
5
6 [2,3]-sigmatropic rearrangement of ynamido-alcohols12 and selective reduction of
7
8
9 amino allenephosphonates for the preparation of α-amino vinylphosphonates.13 These
10
11 α-amino allenephosphonates represent a kind of allenes substituted with both an
12
13
14 electron-withdrawing group and an electron-donating group, thus they would show
15
16 some special reactivity. In the continuation of our investigation of allenamides14 and
17
18
19 ynamides,15 we recently found a novel synthesis of imidazoles from
20
21 electron-withdrawing group substituted allenyl sulfonamides with amines. Herein we
22
23
24 report this regioselective synthesis of highly substituted imidazoles.
25
26 We initiated our studies by examining the reaction of allenyl sulfonamide 4a with
27
28
29 propylamine 5a. No imidazole 6a was detected when 4a and 5a were reacted in
30
31 CH3CN at room temperature (Table 1, entry 1). Fortunately, in the presence of a base
32
33
34 K2CO3, the reaction in refluxing CH3CN gave imidazole 6a in 39% yield (entry 2).
35
36 Addition of 2 equiv of 5a gave better yield (entry 3). Subsequent screening of solvent
37
38
39 and base showed that DMF proved to be the most suitable solvent (entries 4-7) while
40
41
K2CO3 was the best base (entries 8-10). Thus, we concluded that K2CO3 as base in
42
43
44 DMF at 100 oC under air provided the sole product imidazole 6a in the highest yield
45
46
(87%, entry 5).
47
48 Table 1. Optimization of the Reaction Conditionsa
49
50 P(O)Ph2 P(O)Ph2
51 base
52 N Ts + n-PrNH2 N N
solvent n-Pr
53 temp
54 Ph air Ph
55 4a 5a 6a
56
57
entry base solvent temp time yield of 6a (%)
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1
2
3 1 no CH3CN rt 12 h 0
4
5 2 K2CO3 CH3CN reflux 8h 39
6 3 b
K2CO3 CH3CN reflux 8h 54
7
b o
8 4 K2CO3 1,4-dioxane 100 C 2h 66
9
10
5b K2CO3 DMF 100 oC 2h 87
11 b o
6 K2CO3 toluene 100 C 2h 41
12 b o
13 7 K2CO3 DMSO 100 C 2h 75
14 8 b
i-Pr2EtN DMF 100 C o
2h 50
15
b o
16 9 K3PO4 DMF 100 C 2h 72
17
10b Cs2CO3 DMF 100 oC 2h 80
18
19 a
Unless otherwise specified, the reaction was carried out using 4a (0.2 mmol)), 5a (0.2 mmol) and
20 base (0.6 mmol) in solvent (2 mL) under air. b5a (0.4 mmol) was used.
21
22
23 Under the optimized conditions, the scope of this reaction was further investigated.
24
25 A variety of amines including primary alkyl amines (n-PrNH2, n-BuNH2, i-BuNH2,
26
27
28 and PhCH2CH2NH2), secondary alkyl amine (i-PrNH2 and C6H11NH2) and aryl amine
29
30 (p-MeOC6H4NH2 and PhNH2) were all efficiently coupled to furnish the
31
32
33 corresponding products imidazoles (Table 2, entries 1-8, 11). Both α-amino
34
35 allenephosphonates and allenephosphine oxides worked well to afford corresponding
36
37
38 imidazol-4-ylphosphonates and imidazol-4-ylphosphine oxides respectively. R1 and
39
40 R2 groups on the allene moiety could be H, alkyl and aryl group, although bulky
41
42
43 groups resulted in lower yields (entries 9-13). R3 group of 4 could be a substituted
44
45 phenyl group (entries 1, 12). α-Amino allenoates could also undergo this reaction
46
47
48 under modified conditions (entries 14-17). In all reactions in Table 2, the
49
50
4-functionalized imidazoles was obtained as the sole regioisomer and the structure
51
52
53 was revealed by X-ray diffraction of 6c.16
54
55
Table 2. Synthesis of 4-Functionalized Imidazoles 6a
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2
3 R1
R1 EWG
4 K2CO3 R2 EWG
5 R 2
N Ts + R4NH2
DMF, air
6 100 oC or R4 N N
7 R3 rt 125 oC R3
8 4 5 6
9
10 entry 4 5 yield of 6
11 P(O)Ph2 P(O)Ph2
12
N Ts NH2 N N
13
14 Ph Ph
15 1 4a 5a 6a 87%
2b 4a 5a 6a 77%
16
17 P(O)Ph2

18 3 4a
NH2 N N
19
20 Ph
5b 6b 79%
21
P(O)Ph2
22
4 4a NH2
23 N N
24
Ph
25 5c 6c 86%
26 P(O)Ph2
27
NH2
28 5 4a N N
29 Ph
30 5d 6d 30%
31 P(O)Ph2
32 NH2
33 6 4a N N
34 Ph
35
36 5e 6e 53%
37 P(O)Ph2
38 NH2
7 4a N N
39
MeO MeO
40 Ph
41
5f 6f 47%
42
43 P(O)Ph2
44 8 4a PhNH2
Ph N N
45
46 Ph
5g 6g 40%
47
48 P(O)(OEt)2 P(O)(OEt)2
49
50 N Ts N N
9 5a
51 Ph Ph
52 4b 6h 62%
53
54 P(O)(OEt)2 P(O)(OEt)2
55
N Ts N N
56 10 5a
57 Ph Ph
58 4c 6i 58%
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1
2
3 P(O)(OEt)2 P(O)(OEt)2
4 NH2
5 11 N Ts Ph
N N
6 Ph Ph Ph
7 4d 5h 6j 28%
8
9 P(O)(OEt)2 P(O)(OEt)2
10
12 N Ts 5a N N
11
12 C6H4OMe-p C6H4OMe-p
13 4e 6k 48%
14
P(O)(OEt)2 P(O)(OEt)2
15 Ph
16 13 Ph N Ts 5a N N
17
Ph Ph
18
4f 6l 45%
19
20 CO2Pr CO2Pr
21 14c
5a
N Ts N N
22
23 Ph Ph
24 4g 6m 60%
25 CO2Pr
26
15c 4g 5c N N
27
28 Ph
29 6n 65%
30 CO2Pr
31 c
16 4g 5h N N
32
33 Ph Ph
34 6o 57%
35 CO2Pr
CO2Pr
36 17c 5c
37 N Ts N N
38 Ph
Ph
39 4h 6p 73%
40
a
41 Unless otherwise specified, the reaction was carried out using 4 (1.0 equiv), 5 (2.0 equiv) and
42 K2CO3 (3.0 equiv) in DMF at 100 oC under air for 2-9 h. bYield of gram-scale reaction (4a 5.0
43
mmol, 2.498 g). cThe reaction was carried out under air at rt for 1 h and then 125 oC for 4-9 h.
44
45
46 The reaction of allenyl sulfonamide 4g with BnNH2 5i under standard conditions
47
48
afforded the expected imidazole-4-carboxylate 6q. Interestingly, a regioisomer
49
50
51 imidazole-5-carboxylate 7a was also found (Scheme 1).17 The corresponding
52
53
regioisomer was not detected in 1H NMR spectra of the crude reaction mixtures in
54
55
56 cases where other alkyl amines were employed (Table 2).
57
58 Scheme 1. Synthesis of Imidazoles 6q and 7a
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2
3 CO2Pr CO2Pr CO2Pr
4
K2CO3
5 N Ts + BnNH2 + N
DMF, air N N N
6
7 Ph rt, 1h; Ph Ph Ph Ph
8 125 oC, 7 h
9 4g 5i 6q 65% 7a 9%
10
11 Realizing that the substituents on the nitrogen atoms could play an important role
12
13
14 on the regioselectivity, we conducted the reactions of various amines with allenyl
15
16 sulfonamides in which R3 was an alkyl group. As shown in Table 3, N-propyl allenyl
17
18
19 sulfonamides 4i and 4j reacted with substituted benzyl amines 5i-5k to produce
20
21 imidazole-5-carboxylates 7b-7d and imidazol-5-ylphosphine oxide 7g.
22
23
24 2-Picolylamine 5l and allylamine 5m also gave the imidazoles products, albeit in
25
26 lower yields (entries 4 and 5). The structure was revealed by X-ray diffraction of 7g.18
27
28
29 In these cases, the regioisomers 4-functionalized imidazoles were not detected in 1H
30
31 NMR spectra of the crude reaction mixtures. Thus this reaction could regioselectively
32
33
34 construct two regioisomers respectively (e.g. 6a and 7g; 6m and 7b) just by
35
36 exchanging the substituents on the two nitrogen atoms. However, the reaction of
37
38
39 allenyl sulfonamide 4i with alkyl amine such as n-PrNH2 5a resulted in unidentified
40
41
mixture (entry 7), indicating that at least one Bn or allyl group on the nitrogen atoms
42
43
44 was necessary for this transformation.
45
46
Table 3. Synthesis of 5-Functionalized Imidazoles 7a
47
48 EWG EWG
49 K2CO3
50 N Ts + R5 NH2 N N
DMF, air
51 100 oC or
52 R5
rt 125 oC
53 4 5 7
54
55 entry 4 EWG 5 R5 Yield of 7 (%)
56
57 1 4i CO2Pr 5i Ph 7b 57
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2
3 2 4i CO2Pr 5j 4-ClC6H4 7c 53
4
5 3 4i CO2Pr 5k 3-MeOC6H4 7d 47
6 4 4i CO2Pr 5l 2-pyridinyl 7e 37
7
8 5 4i CO2Pr 5m vinyl 7f 20
9
6b 4j P(O)Ph2 5i Ph 7g 36
10
11 7 4i CO2Pr 5a Et unidentified mixture
12 a
13 Unless otherwise specified, the reaction was carried out using 4 (1.0 equiv), 5 (2.0 equiv) and
14 K2CO3 (3.0 equiv) in DMF under air at rt for 1 h and then 125 oC for 6-9 h. bThe reaction was
15 carried out at 100 oC for 3 h.
16
17
18 To gain more insight into the reaction mechanism, we attempted to isolate the
19
20 intermediate addition product of allenyl sulfonamides 4g and 4i with amines 5i and 5c
21
22
23 (Scheme 2). Without a base, the reaction at room temperature gave the addition
24
25 product 8a-8c19 (the structure was revealed by X-ray diffraction of 8a20) in high yield
26
27
28 and no imidazole was found. Under the standard conditions, 8a-8c were converted to
29
30 imidazoles 6 and/or 7. The regioselectivity was consistent with the results of the
31
32
33 one-pot reactions, indicating that 8 was the intermediate of this sequential reaction.
34
35 Scheme 2. Isolation of the Intermediate 8
36
R5
37
K2CO3 CO2Pr CO2Pr
38 CO2Pr
DMF HN CO2Pr
39 DMF, air
+ R5 NH2 N N + N N
40 N Ts rt, 1 h 125 oC
N Ts 5
41 5h R R3 R5 R3
42 R3 R3
43
4g R3 = Ph 5i R5 = Ph 8a 86% 6q 62% 7a 8%
44
4g R3 = Ph 5c R5 = i-Pr 8b 79% 6n 83% --
45 4i R3 = Et 5i R5 = Ph 8c 84% -- 7b 72%
46
47 On the basis of the above experimental observations, the following plausible
48
49
50 mechanism was proposed for this reaction as shown in Scheme 3. Initially, the
51
52 addition reaction of allenyl sulfonamide 4 with amine 5 affords the intermediate A. In
53
54
55 the presence of K2CO3, elimination of one molecule of 4-methylbenzenesulfinic
56
57 acid21 provides an unstable diimine B. Depending on the nature of substitutents R3
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2
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4 and R5, B could be further converted to either C or D via 1,5-H shift, followed by
5
6 concomitant ring closure. Imidazoles 6 or 7 are thus forged through oxidative
7
8
9 aromatization under open air condition. Roles of substituents R3 and R5 are extremely
10
11 important for the product distribution. (i) When either R3 or R5 is an aryl or vinyl
12
13
14 group, benzylic or allylic proton may facilitate 1,5-H shift, leading to intermediate C
15
16 or D respectively. (ii) Path a and path b coexist, if both R3 and R5 are aryl groups,
17
18
19 generating two sets of imidazoles. However, due to the electron withdrawing effect of
20
21 the attached ester group, the proton adjacent to R3 shows stronger acidity, resulting in
22
23
24 the predominance of intermediate C. (iii) In the case that neither R3 nor R5 is an aryl
25
26 group, 1,5-H shift process may be inhibited without an activated proton, therefore no
27
28
29 imidazole is produced.
30
31 Scheme 3. Possible Mechanism
32
33 EWG EWG EWG
34
K2CO3
35 N Ts NH N Ts N N
R 5
NH2 5 -TsH
36 R
37 5 R3 3 R5 R3
4 A R B
38
EWG EWG
39 oxidative
40 path a aromatization
NH N N NH 6
41 R3 = aryl R5 O2
5
42 R R3
1,5- R3
43 C E
44 H-shift
EWG EWG oxidative
45 path b aromatization
46 N HN HN N 7
R5 = aryl O2
47 R3
R5 R5 R3
48
49 D F
50
51 In conclusion, we have described a novel regioselective synthesis of highly
52
53
substituted imidazoles from electron-withdrawing group substituted allenyl
54
55
56 sulfonamides with amines. The imidazol-4- or imidazol-5-ylphosphonates, phosphine
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2
3
4 oxides and carboxylates were constructed regioselectively depending on the
5
6 substituents on the nitrogen atoms.
7
8
9
10
11 EXPERIMENTAL SECTION
12
13
14 General: All commercially available chemicals and reagents were used without any
15
16 further purification. NMR spectra were recorded on a 400 MHz or 500 MHz NMR
17
18
19 spectrometer using tetramethylsilane as the internal standard and CDCl3 as solvent.
20
21 Chemical shifts were expressed in ppm and J values were given in Hz. High
22
23
24 resolution mass spectrometry (HRMS) was obtained using the ESI- or EI- or
25
26 APCI-TOF method. Melting points were measured on a microscopic apparatus and
27
28
29 were uncorrected.
30
31 Preparation of the α-amino allenephosphonates and phosphine oxides was done
32
33
34 according to Rabasso’s method.12 Characterization of unreported α-amino allene
35
36 phosphine oxide is listed below.
37
38
39 N-(1-(Diphenylphosphoryl)propa-1,2-dienyl)-4-methyl-N-propylbenzenesulfona
40
mide (4j). Colorless solid (556.6 mg, 56%): mp 146-148 oC. 1H NMR (400 MHz,
41
42 CDCl3): δ 7.81-7.85 (m, 4H), 7.59-7.61 (m, 2H), 7.44-7.51 (m, 6H), 7.17-7.19 (m,
43
44 2H), 5.07 (s, 1H), 5.05 (s, 1H), 3.33 (t, J = 8.0 Hz, 2H), 2.34 (s, 3H), 1.45-1.55 (m,
45
46 2H), 0.73 (t, J = 8.0 Hz, 3H); 13C NMR (100 MHz, CDCl3): δ 214.0 (d, J = 22.0 Hz),
47
48 143.6, 135.7, 132.1, 131.9, 130.8, 129.3, 128.3, 128.0, 103.9 (d, J = 124.0 Hz), 84.0
49
50 (d, J = 9.6 Hz), 52.2, 21.5, 21.2, 11.0; IR (KBr): ν (cm−1) 3060, 2980, 1384, 1197,
51
52 1157, 555, 524; HRMS (EI-TOF) m/z: M+ Calcd for C25H26NO3PS 451.1371; Found
53
54 451.1363.
55
56 Propyl 2-(N-benzyl-4-methylphenylsulfonamido)buta-2,3-dienoate (4g). Typical
57
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2
3
4 Procedure.
5
6 Ts CO2Pr
Pd(PPh3)4
7 N
Bn CO,PrOH
8 PrO2CO N Ts
rt
9 Bn
10
11 To a flame-dried Schlenk flask were added 3-(N-benzyl-4-methylphenylsulfonamido)
12
13
14 prop-2-ynyl propyl carbonate14 (200.8 mg, 0.5 mmol) and Pd(PPh3)4 (28.9 mg, 0.025
15
16 mmol). After addition of each chemical, the flask was degassed and refilled with CO
17
18
19 by a balloon of CO (about 1 L) for three times. Then PrOH (1 mL) was added and the
20
21 resulting mixture was stirred at rt for 24 h. After that, the resulting mixture was
22
23
24 filtered through a short pad of silica gel, eluted with EtOAc (20 mL), and
25
26 concentrated. The residue was purified by column chromatography on silica gel with
27
28
29 hexane/EtOAc (9:1, v:v) as the eluent to get 4g (48.0 mg, 25%) as a yellow oil. 1H
30
31 NMR (400 MHz, CDCl3): δ 7.80 (d, J = 8.4 Hz, 2H), 7.32 (d, J = 8.4 Hz, 2H),
32
33
34 7.24-7.26 (m, 5H), 5.21 (s, 2H), 4.44 (s, 2H), 4.03 (t, J = 6.8 Hz, 2H), 2.44 (s, 3H),
35
36 1.57-1.62 (m, 2H), 0.89 (t, J = 7.2 Hz, 3H); 13C NMR (100 MHz, CDCl3): δ 214.8,
37
38
39 163.9, 143.8, 135.5, 135.4, 129.5, 128.6, 128.4, 128.0, 127.8, 104.6, 84.5, 67.1, 53.2,
40
41
21.9, 21.6, 10.3; IR (neat): ν (cm−1) 2968, 1719, 1349, 1268, 1161, 1090, 666; HRMS
42
43
44 (ESI-TOF) m/z: [M + H]+ Calcd for C21H24NO4S 386.1421; Found 386.1420.
45
46 Propyl 2-(N-benzyl-4-methylphenylsulfonamido)penta-2,3-dienoate (4h). Yellow
47
48 oil (61.9 mg, 33%). 1H NMR (400 MHz, CDCl3): δ 7.79 (d, J = 8.0 Hz, 2H),
49
50 7.22-7.33 (m, 7H), 5.59 (q, J = 7.6 Hz, 1H), 4.44 (s, 2H), 4.02 (t, J = 6.8 Hz, 2H),
51
52 2.43 (s, 3H), 1.58-1.62 (m, 2H), 1.50 (d, J = 7.6 Hz, 3H), 0.89 (t, J = 7.6 Hz, 3H); 13C
53
54 NMR (100 MHz, CDCl3): δ 211.1, 164.3, 143.7, 135.7, 135.6, 129.5, 128.5, 128.3,
55
56 128.0, 127.7, 103.3, 96.0, 66.9, 52.9, 21.9, 21.6, 12.9, 10.3; IR (neat): ν (cm−1) 2967,
57
1718, 1349, 1270, 1161, 1091, 665; HRMS (ESI-TOF) m/z: [M + H]+ Calcd for
58
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2
3 C22H26NO4S 400.1577; Found 400.1573.
4
5 Propyl 2-(4-methyl-N-propylphenylsulfonamido)buta-2,3-dienoate (4i). Yellow oil
6
7 (37.7 mg, 22%). 1H NMR (400 MHz, CDCl3): δ 7.73 (d, J = 8.0 Hz, 2H), 7.29 (d, J =
8
9 8.0 Hz, 2H), 5.35 (s, 2H), 4.11 (t, J = 6.8 Hz, 2H), 3.21 (t, J = 7.2 Hz, 2H), 2.42 (s,
10
11 3H), 1.49-1.68 (m, 4H), 0.87-0.96 (m, 6H); 13C NMR (125 MHz, CDCl3): δ 214.4,
12
13 164.2, 143.5, 135.5, 129.3, 127.9, 104.7, 84.4, 67.2, 51.2, 21.9, 21.5, 21.4; IR (neat): ν
14
15 (cm−1) 2967, 1722, 1347, 1267, 1154, 1088, 1010; HRMS (APCI-TOF) m/z: [M +
16
17 H]+ Calcd for C17H24NO4S 338.1421; Found 338.1434.
18
19
4-(Diphenylphosphoryl)-5-methyl-2-phenyl-1-propyl-1H-imidazole (6a). Typical
20 Procedure. To the solution of α-amino allenephosphine oxides 4a (99.9 mg, 0.2
21
22 mmol) in DMF (2 mL) was added amine 5a (23.6 mg, 0.4 mmol) and K2CO3 (82.8 mg,
23
24 0.6 mmol) and the solution was stirred at 100 oC under air. Upon reaction completion
25
26 (2 h, TLC, eluent: hexane-EtOAc, 1:1), the mixture was filtered over a plug of silica
27
28 gel (washed with 50 mL EtOAc), and the filtrate was washed with brine, dried over
29
30 Na2SO4, filtered and concentrated. The residue was purified by column
31
32 chromatography on silica gel with hexane/EtOAc (1:1~1:2, v:v) as the eluent to get 6a
33
34 (69.7 mg, 87%) as a colorless solid, mp 142-144 oC. 1H NMR (400 MHz, CDCl3): δ
35
7.94-7.98 (m, 4H), 7.51-7.52 (m, 2H), 7.35-7.46 (m, 9H), 3.84 (t, J = 7.6 Hz, 2H),
36
37 2.64 (s, 3H), 1.61-1.63 (m, 2H), 0.80 (t, J = 7.2 Hz, 3H); 13C NMR (100 MHz,
38
39 CDCl3): δ 149.0 (d, J = 18.5 Hz), 139.7 (d, J = 27.2 Hz), 134.6 (d, J = 106.5 Hz),
40
41 131.7 (d, J = 9.7 Hz), 131.3, 131.0, 129.11, 129.07, 128.6, 128.1 (d, J = 12.1 Hz),
42
43 126.7, 46.0, 23.9, 11.1, 10.2; IR (KBr): ν (cm−1) 2969, 1438, 1176, 699, 568, 529;
44
45 HRMS (EI-TOF) m/z: M+ Calcd for C25H25N2OP 400.1705; Found 400.1709.
46
47 1-Butyl-4-(diphenylphosphoryl)-5-methyl-2-phenyl-1H-imidazole (6b). Colorless
48
49 solid (81.5 mg, 79%): mp 155-157 oC. 1H NMR (400 MHz, CDCl3): δ 7.93-7.98 (m,
50
51
4H), 7.51-7.53 (m, 2H), 7.38-7.45 (m, 9H), 3.89 (t, J = 8.0 Hz, 2H), 2.64 (s, 3H),
52
1.58-1.62 (m, 2H), 1.19-1.25 (m, 2H), 0.83 (t, J = 7.2 Hz, 3H); 13C NMR (100 MHz,
53
54 CDCl3): δ 148.9 (d, J = 18.6 Hz), 139.6 (d, J = 27.0 Hz), 134.9 (d, J = 106.5 Hz),
55
56 131.7 (d, J = 9.9 Hz), 131.2 (d, J = 2.7 Hz), 131.1, 129.1, 129.0, 128.6, 128.1 (d, J =
57
58 12.0 Hz), 127.7 (d, J = 157.9 Hz), 44.2, 32.5, 19.8, 13.5, 10.2; IR (KBr): ν (cm−1)
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3 2967, 1541, 1436, 1366, 1171, 1117, 697; HRMS (ESI-TOF) m/z: [M + H]+ Calcd for
4
5 C26H28N2OP 415.1934; Found 415.1924.
6
7 4-(Diphenylphosphoryl)-1-isobutyl-5-methyl-2-phenyl-1H-imidazole (6c).
8
9 Colorless solid (88.6 mg, 86%): mp 161-163 oC. 1H NMR (400 MHz, CDCl3): δ
10
11 7.91-7.97 (m, 4H), 7.50-7.52 (m, 2H), 7.38-7.44 (m, 9H), 3.81 (d, J = 7.6 Hz, 2H),
12
13 2.63 (s, 3H), 1.77-1.81 (m, 1H), 0.68 (d, J = 6.8 Hz, 6H); 13C NMR (100 MHz,
14
15 CDCl3): δ 149.2 (d, J = 18.3 Hz), 139.9 (d, J = 26.9 Hz), 134.9 (d, J = 106.4 Hz),
16
17 131.7 (d, J = 9.7 Hz), 131.6, 131.2 (d, J = 2.5 Hz), 129.3, 128.9, 128.5, 128.1 (d, J =
18
12.2 Hz), 127.7 (d, J = 148.3 Hz), 51.3, 29.1, 19.7, 10.6; IR (KBr): ν (cm−1) 2970,
19
20 1542, 1436, 1261, 1181, 1117, 780, 698; HRMS (ESI-TOF) m/z: [M + H]+ Calcd for
21
22 C26H28N2OP 415.1934; Found 415.1927.
23
24 4-(Diphenylphosphoryl)-1-isopropyl-5-methyl-2-phenyl-1H-imidazole (6d).
25
26 Colorless solid (51.3 mg, 30%): mp 193-195 oC. 1H NMR (500 MHz, CDCl3): δ
27
28 7.95-7.99 (m, 4H), 7.41-7.48 (m, 11H), 4.57-4.61 (m, 1H), 2.79 (s, 3H), 1.48 (d, J =
29
30 7.0 Hz, 6H); 13C NMR (125 MHz, CDCl3): δ 149.3 (d, J = 18.9 Hz), 139.1 (d, J =
31
32 27.5 Hz), 134.9 (d, J = 106.4 Hz), 131.8, 131.7, 131.2, 129.8, 129.1, 128.4, 128.5 (d,
33
34 J = 147.2 Hz), 128.1 (d, J = 11.9 Hz), 48.9, 22.0, 11.8; IR (KBr): ν (cm−1) 3049, 2967,
35
1368, 1166, 1135, 703, 535; HRMS (EI-TOF) m/z: M+ Calcd for C25H25N2OP
36
37 400.1705; Found: 400.1697.
38
39 1-Cyclohexyl-4-(diphenylphosphoryl)-5-methyl-2-phenyl-1H-imidazole (6e).
40
41 Yellow oil (70.0 mg, 53%). 1H NMR (400 MHz, CDCl3): δ 7.82-7.88 (m, 4H),
42
43 7.28-7.33 (m, 11H), 4.00-4.02 (m, 1H), 2.68 (s, 3H), 1.71-1.84 (m, 6H), 1.53-1.56 (m,
44
45 1H), 1.03-1.12 (m, 3H); 13C NMR (100 MHz, CDCl3): δ 149.5 (d, J = 18.8 Hz), 139.2
46
47 (d, J = 27.1 Hz), 134.8 (d, J = 106.3 Hz), 131.8, 131.7, 131.2 (d, J = 2.7 Hz), 129.7,
48
49 129.1, 128.4, 128.3 (d, J = 151.0 Hz), 128.1 (d, J = 12.0 Hz), 57.8, 32.1, 26.1, 25.1,
50
51
12.1; IR (neat): ν (cm−1) 3051, 2965, 1344, 1159, 1130, 704; HRMS (ESI-TOF) m/z:
52
[M + H]+ Calcd for C28H30N2OP 441.2090; Found: 441.2091.
53
54 4-(Diphenylphosphoryl)-1-(4-methoxyphenyl)-5-methyl-2-phenyl-1H-imidazole
55
56 (6f). Yellow oil (65.9 mg, 47%). 1H NMR (400 MHz, CDCl3): δ 8.02-8.07 (m, 4H),
57
58 7.43-7.46 (m, 6H), 7.34-7.36 (m, 2H), 7.18-7.20 (m, 3H), 7.08 (d, J = 8.8 Hz, 2H),
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3 6.93 (d, J = 8.8 Hz, 2H), 3.81 (s, 3H), 2.38 (s, 3H); 13C NMR (125 MHz, CDCl3): δ
4
5 159.9, 148.3 (d, J = 17.7 Hz), 141.5 (d, J = 26.9 Hz), 134.7 (d, J = 106.5 Hz), 131.8,
6
7 131.7, 131.3 (d, J = 2.4 Hz), 130.3, 129.2, 129.0, 128.4, 128.2, 128.1 (d, J = 3.7 Hz),
8
9 128.0 (d, J = 147.9 Hz), 114.9, 55.5, 10.7; IR (neat): ν (cm−1) 3029, 1513, 1437, 1250,
10
11 1170, 1120, 692; HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C29H26N2O2P 465.1726;
12
13 Found: 465.1730.
14
15 4-(Diphenylphosphoryl)-5-methyl-1,2-diphenyl-1H-imidazole (6g). Yellow oil
16
17 (51.9 mg, 40%). 1H NMR (400 MHz, CDCl3): δ 7.94-8.00 (m, 4H), 7.36-7.41 (m, 9H),
18
7.22-7.25 (m, 2H), 7.09-7.14 (m, 5H), 2.32 (s, 3H); 13C NMR (100 MHz, CDCl3): δ
19
20 148.1 (d, J = 17.8 Hz), 141.1 (d, J = 26.9 Hz), 136.7, 134.7 (d, J = 106.6 Hz), 131.8,
21
22 131.7, 131.3 (d, J = 2.6 Hz), 130.2, 129.8, 129.2, 128.4, 128.3, 128.2 (d, J = 147.4
23
24 Hz), 128.1, 128.0 (d, J = 13.1 Hz), 10.7; IR (neat): ν (cm−1) 3027, 1510, 1435, 1244,
25
26 1169, 690; HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C28H24N2OP 435.1621; Found:
27
28 435.1614.
29
30 Diethyl 5-methyl-2-phenyl-1-propyl-1H-imidazol-4-ylphosphonate (6h). Yellow
31
32 oil (52.0 mg, 62%). 1H NMR (400 MHz, CDCl3): δ 7.52-7.54 (m, 2H), 7.43-7.45 (m,
33
34 3H), 4.15-4.23 (m, 4H), 3.87 (t, J = 7.6 Hz, 2H), 2.58 (s, 3H), 1.61-1.67 (m, 2H), 1.35
35
(t, J = 7.5 Hz, 6H), 0.82 (t, J = 7.2 Hz, 3H); 13C NMR (100 MHz, CDCl3): δ 149.1 (d,
36
37 J = 22.1 Hz), 138.8 (d, J = 38.7 Hz), 130.8, 129.1, 129.0, 128.5, 125.2 (d, J = 243.8
38
39 Hz), 62.0 (d, J = 5.6 Hz), 46.1, 23.7, 16.2 (d, J = 6.5 Hz), 10.9, 10.1; IR (neat): ν
40
41 (cm−1) 3010, 1470, 1277, 1235, 1023, 957, 784; HRMS (ESI-TOF) m/z: [M + H]+
42
43 Calcd for C17H26N2O3P 337.1676; Found: 337.1657.
44
45 Diethyl 5-ethyl-2-phenyl-1-propyl-1H-imidazol-4-ylphosphonate (6i). Yellow oil
46
47 (201.5 mg, 58%). 1H NMR (400 MHz, CDCl3): δ 7.54-7.56 (m, 2H), 7.41-7.45 (m,
48
49 3H), 4.14-4.25 (m, 4H), 3.90 (t, J = 8.0 Hz, 2H), 3.01 (q, J = 7.6 Hz, 2H), 1.57-1.63
50
51
(m, 2H), 1.26-1.36 (m, 9H), 0.80 (t, J = 7.6 Hz, 3H); 13C NMR (100 MHz, CDCl3): δ
52
148.8 (d, J = 22.2 Hz), 144.6 (d, J = 39.0 Hz), 130.9, 129.0, 128.9, 128.4, 124.5 (d, J
53
54 = 243.1 Hz), 61.8 (d, J = 5.6 Hz), 45.9, 24.1, 17.4, 16.2 (d, J = 6.4 Hz), 15.1, 10.8; IR
55
56 (neat): ν (cm−1) 2968, 1476, 1237, 1025, 948, 762; HRMS (ESI-TOF) m/z: [M + H]+
57
58 Calcd for C18H28N2O3P 351.1832; Found: 351.1839.
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3
Diethyl 5-isopropyl-1-phenethyl-2-phenyl-1H-imidazol-4-ylphosphonate (6j).
4
5 Colorless solid (59.2 mg, 28%): mp 230-232 oC. 1H NMR (500 MHz, CDCl3): δ
6
7 7.44-7.48 (m, 5H), 7,21-7.22 (m, 3H), 6.87 (d, J = 10.0 Hz, 2H), 4.15-4.24 (m, 6H),
8
9 3.55-3.58 (m, 1H), 2.78 (t, J = 8.0 Hz, 2H), 1.50 (d, J = 7.5 Hz, 6H), 1.36 (t, J = 7.0
10
11 Hz, 6H); 13C NMR (125 MHz, CDCl3): δ 148.6 (d, J = 22.4 Hz), 147.6 (d, J = 39.5
12
13 Hz), 136.9, 131.0, 129.4, 129.2, 128.2, 128.5, 128.4, 127.0, 124.6 (d, J = 242.5 Hz),
14
15 62.1 (d, J = 5.5 Hz), 46.4, 37.2, 25.3, 21.9, 16.4 (d, J = 6.5 Hz); IR (KBr): ν (cm−1)
16
17 3031, 2927, 1263, 1227, 1055, 1027, 973; HRMS (EI-TOF) m/z: M+ Calcd for
18
C24H31N2O3P 426.2072; Found: 426.2068.
19
20 Diethyl 5-isopropyl-2-(4-methoxyphenyl)-1-propyl-1H-imidazol-4-ylphosphonate
21
22 (6k). Yellow oil (144.3 mg, 48%). 1H NMR (500 MHz, CDCl3): δ 7.45 (d, J = 8.5 Hz,
23
24 2H), 6.96 (d, J = 8.5 Hz, 2H), 4.13-4.22 (m, 4H), 3.85-3.89 (m, 5H), 3.42-3.46 (m,
25
26 1H), 1.58-1.63 (m, 2H), 1.50 (d, J = 9.5 Hz, 6H), 1.35 (t, J = 7.0 Hz, 6H), 0.83 (t, J =
27
28 7.5 Hz, 3H); 13C NMR (125 MHz, CDCl3): δ 160.2, 148.3 (d, J = 22.1 Hz), 147.6 (d,
29
30 J = 39.0 Hz), 130.7, 124.1 (d, J = 243.1 Hz), 123.6, 113.9, 62.0 (d, J = 5.5 Hz), 55.3,
31
32 46.5, 25.2, 24.4, 21.8, 16.3 (d, J = 6.5 Hz), 11.0; IR (neat): ν (cm−1) 2926, 1456, 1266,
33
34 1050, 1022, 966; HRMS (EI-TOF) m/z: M+ Calcd for C20H31N2O4P 394.2021; Found:
35
394.2014.
36
37 Diethyl 2-phenyl-5-(1-phenylethyl)-1-propyl-1H-imidazol-4-ylphosphonate (6l).
38
39 Yellow oil (47.7 mg, 45%). 1H NMR (500 MHz, CDCl3): δ 7.51 (d, J = 4.0 Hz, 2H),
40
41 7.28-7.39 (m, 7H), 7.19-7.22 (m, 1H), 5.42 (q, J = 7.5 Hz, 1H), 4.18-4.29 (4H, m),
42
43 3.63 (t, J = 8.5 Hz, 2H), 1.80 (d, J = 7.5 Hz, 3H), 1.34-1.40 (m, 6H), 1.03-1.07 (m,
44
45 1H), 0.62-0.66 (m, 1H), 0.37 (t, J = 7.5 Hz, 3H); 13C NMR (100 MHz, CDCl3): δ
46
47 149.6 (d, J = 22.2 Hz), 145.3 (d, J = 38.9 Hz), 141.9, 131.0, 129.1, 128.9, 128.5,
48
49 127.3, 124.6, 125.7 (d, J = 242.3 Hz), 62.2, 46.8, 33.6, 23.0, 18.3, 16.4, 10.8; IR
50
51
(neat): ν (cm−1) 2973, 1226, 1023, 961, 779, 762, 699; HRMS (EI-TOF) m/z: M+
52
Calcd for C24H31N2O3P 426.2072; Found: 426.2068.
53
54 5-(Diphenylphosphoryl)-4-methyl-2-phenyl-1-propyl-1H-imidazole (7g).
55
56 Colorless solid (36.0 mg, 36%): mp 152-154 oC. 1H NMR (500 MHz, CDCl3): δ
57
58 7.68-7.73 (m, 4H), 7.42-7.57 (m, 11H), 4.24 (t, J = 7.0 Hz, 2H), 1.60 (s, 3H),
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3 1.38-1.42 (m, 2H), 0.52 (t, J = 7.0 Hz, 3H); 13C NMR (125 MHz, CDCl3): δ 152.1 (d,
4
5 J = 11.1 Hz), 147.6 (d, J = 15.2 Hz), 133.0 (d, J = 110.1 Hz), 132.3 (d, J = 2.6 Hz),
6
7 131.9 (d, J = 10.5 Hz), 130.5, 129.3, 129.1, 128.8 (d, J = 12.4 Hz), 128.6, 117.6 (d, J
8
9 = 123.0 Hz), 48.1, 24.6, 15.4, 10.7; IR (KBr): ν (cm−1) 2981, 2870, 1245, 724, 700,
10
11 559, 530; HRMS (EI-TOF) m/z: M+ Calcd for C25H25N2OP 400.1705; Found:
12
13 400.1702.
14
15 Propyl 5-methyl-2-phenyl-1-propyl-1H-imidazole-4-carboxylate (6m). Typical
16
17 Procedure. To the solution of α-amino allene carboxylate 4g (119.3 mg, 0.3 mmol) in
18
19
DMF (2 mL) was added amine 5a (35.5 mg, 0.6 mmol) and K2CO3 (124.4 mg, 0.9
20 mmol) and the solution was stirred at room temperature for 1 h and then 125 oC under
21
22 air. Upon reaction completion (7 h, TLC, eluent: hexane-EtOAc, 1:1), the mixture
23
24 was filtered over a plug of silica gel (washed with 50 mL EtOAc), and the filtrate was
25
26 washed with brine, dried over Na2SO4, filtered and concentrated. The residue was
27
28 purified by column chromatography on silica gel with hexane/EtOAc (1:1~1:2, v:v) as
29
30 the eluent to get 6m (51.6 mg, 60%) as a yellow oil. 1H NMR (400 MHz, CDCl3): δ
31
32 7.44-7.46 (m, 2H), 7.33-7.35 (m, 3H), 4.20 (t, J = 6.8 Hz, 2H), 3.79 (t, J = 7.6 Hz,
33
34 2H), 2.52 (s, 3H), 1.69-1.75 (m, 2H), 1.51-1.56 (m, 2H), 0.91 (t, J = 7.2 Hz, 3H), 0.72
35
(t, J = 7.6 Hz, 3H); 13C NMR (100 MHz, CDCl3): δ 164.1, 147.4, 136.3, 130.7, 129.3,
36
37 129.1, 128.8, 128.4, 65.8, 46.0, 23.7, 22.2, 10.9, 10.5, 10.4; IR (neat): ν (cm−1) 2950,
38
39 1699, 1570, 1199, 1153, 1066, 711; HRMS (ESI-TOF) m/z: [M + H]+ Calcd for
40
41 C17H23N2O2 287.1754; Found: 287.1745.
42
43 Propyl 1-isobutyl-5-methyl-2-phenyl-1H-imidazole-4-carboxylate (6n). Colorless
44
45 solid (92.0 mg, 65%): mp 112-114 oC. 1H NMR (400 MHz, CDCl3): δ 7.52-7.54 (m,
46
47 2H), 7.41-7.42 (m, 3H), 4.29 (t, J = 7.2 Hz, 2H), 3.80 (d, J = 7.6 Hz, 2H), 2.60 (s, 3H),
48
49 1.78-1.84 (m, 3H), 0.99 (t, J = 7.2 Hz, 3H), 0.69 (d, J = 6.4 Hz, 6H); 13C NMR (125
50
51
MHz, CDCl3): δ 164.2, 147.7, 136.6, 131.1, 129.5, 129.0, 128.7, 128.4, 65.8, 51.4,
52
29.1, 22.2, 19.6, 10.8, 10.4; IR (KBr): ν (cm−1) 2972, 1689, 1332, 1205, 1070, 785;
53
54 HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C18H25N2O2 301.1911; Found: 301.1900.
55
56 Propyl 5-methyl-1-phenethyl-2-phenyl-1H-imidazole-4-carboxylate (6o).
57
58 Colorless solid (59.5 mg, 57%): mp 94-96 oC. 1H NMR (400 MHz, CDCl3): δ
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3 7.40-7.45 (m, 5H), 7.19-7.20 (m, 3H), 6.86-6.88 (m, 2H), 4.28 (t, J = 7.2 Hz, 2H),
4
5 4.13 (t, J = 7.6 Hz, 2H), 2.79 (t, J = 7.2 Hz, 2H), 2.49 (s, 3H), 1.78-1.83 (m, 2H), 0.99
6
7 (d, J = 7.6 Hz, 3H); 13C NMR (125 MHz, CDCl3): δ 164.1, 147.4, 136.8, 136.4, 130.6,
8
9 129.3, 129.2, 128.8, 128.7, 128.6, 128.4, 127.0, 65.8, 45.8, 36.6, 22.2, 10.5, 10.4; IR
10
11 (KBr): ν (cm−1) 2969, 1710, 1405, 1335, 1166, 1104, 1074; HRMS (ESI-TOF) m/z:
12
13 [M + H]+ Calcd for C22H25N2O2 349.1911; Found: 349.1907.
14
15 Propyl 5-ethyl-1-isobutyl-2-phenyl-1H-imidazole-4-carboxylate (6p). Colorless
16
17 solid (115.0 mg, 73%): mp 71-73 oC. 1H NMR (400 MHz, CDCl3): δ 7.45-7.46 (m,
18
2H), 7.30-7.36 (m, 3H), 4.21 (t, J = 6.8 Hz, 2H), 3.73 (d, J = 7.2 Hz, 2H), 2.95 (q, J =
19
20 7.6 Hz, 2H), 1.71-1.74 (m, 3H), 1.18 (t, J = 7.2 Hz, 3H), 0.92 (t, J = 7.2 Hz, 3H), 0.60
21
22 (d, J = 6.0 Hz, 6H); 13C NMR (100 MHz, CDCl3): δ 163.9, 147.6, 142.5, 131.2, 129.4,
23
24 129.0, 128.4, 128.1, 65.8, 51.4, 29.4, 22.2, 19.6, 18.0, 14.0, 10.4; IR (KBr): ν (cm−1)
25
26 2971, 1692, 1336, 1199, 1090, 1009, 784; HRMS (ESI-TOF) m/z: [M + H]+ Calcd for
27
28 C19H27N2O2 315.2067; Found: 315.2060.
29
30 Propyl 1-benzyl-5-methyl-2-phenyl-1H-imidazole-4-carboxylate (6q). Colorless
31
32 solid (138.1 mg, 65%): mp 96-98 oC. 1H NMR (400 MHz, CDCl3): δ 7.49-7.52 (m,
33
34 2H), 7.28-7.36 (m, 6H), 6.96 (d, J = 7.2 Hz, 2H), 5.18 (s, 2H), 4.30 (t, J = 6.8 Hz, 2H),
35
2.45 (s, 3H), 1.78-1.84 (m, 2H), 1.00 (t, J = 7.6 Hz, 3H); 13C NMR (125 MHz,
36
37 CDCl3): δ 164.1, 148.1, 136.9, 136.0, 130.0, 129.27, 129.24, 129.1, 128.5, 127.8,
38
39 125.5, 65.9, 48.0, 22.2, 10.5, 10.4; IR (KBr): ν (cm−1) 2960, 1692, 1572, 1404, 1326,
40
41 1206, 1068; HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C21H23N2O2 335.1754;
42
43 Found: 335.1750.
44
45 Propyl 1-benzyl-4-methyl-2-phenyl-1H-imidazole-5-carboxylate (7a). Yellow oil
46
47 (19.8 mg, 9%). 1H NMR (400 MHz, CDCl3): δ 7.49-7.52 (m, 2H), 7.23-7.41 (m, 6H),
48
49 6.95 (d, J = 7.2 Hz, 2H), 5.58 (s, 2H), 4.14 (t, J = 6.4 Hz, 2H), 2.60 (s, 3H), 1.62-1.68
50
51
(m, 2H), 0.94 (t, J = 7.2 Hz, 3H); 13C NMR (125 MHz, CDCl3): δ 161.1, 151.4, 148.2,
52
138.1, 129.8, 129.6, 129.2, 128.7, 128.6, 127.2, 125.6, 119.6, 65.9, 49.7, 22.0, 16.1,
53
54 10.6; IR (neat): ν (cm−1) 2957, 1697, 1452, 1416, 1274, 1163, 1098; HRMS (ESI-TOF)
55
56 m/z: [M + H]+ Calcd for C21H23N2O2 335.1754; Found: 335.1757.
57
58 Propyl 4-methyl-2-phenyl-1-propyl-1H-imidazole-5-carboxylate (7b). Yellow oil
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3 (83.0 mg, 57%). 1H NMR (400 MHz, CDCl3): δ 7.53-7.55 (m, 2H), 7.46-7.48 (m, 3H),
4
5 4.23-4.28 (m, 4H), 2.55 (s, 3H), 1.68-1.83 (m, 4H), 1.05 (t, J = 7.6 Hz, 3H), 0.78 (t, J
6
7 = 7.6 Hz, 3H); 13C NMR (100 MHz, CDCl3): δ 161.5, 150.9, 148.0, 130.4, 129.4,
8
9 129.3, 128.6, 119.1, 65.9, 47.9, 24.7, 22.2, 16.1, 10.9, 10.7; IR (neat): ν (cm−1) 2965,
10
11 1696, 1420, 1268, 1189, 1118, 1093; HRMS (ESI-TOF) m/z: [M + H]+ Calcd for
12
13 C17H23N2O2 287.1754; Found: 287.1737.
14
15 Propyl 2-(4-chlorophenyl)-4-methyl-1-propyl-1H-imidazole-5-carboxylate (7c).
16
17 Colorless solid (68.4 mg, 53%): mp 57-59 oC. 1H NMR (400 MHz, CDCl3): δ
18
7.44-7.51 (m, 4H), 4.21-4.28 (m, 4H), 2.54 (s, 3H), 1.67-1.83 (m, 4H), 1.05 (t, J = 7.6
19
20 Hz, 3H), 0.79 (t, J = 7.2 Hz, 3H); 13C NMR (100 MHz, CDCl3): δ 161.3, 149.7, 148.0,
21
22 135.6, 130.6, 128.9, 119.4, 66.0, 47.9, 24.7, 22.1, 16.1, 10.9, 10.7; IR (KBr): ν (cm−1)
23
24 2970, 1698, 1468, 1407, 1267, 1189, 1127, 842; HRMS (ESI-TOF) m/z: [M + H]+
25
26 Calcd for C17H22ClN2O2 321.1364; Found: 321.1355.
27
28 Propyl 2-(3-methoxyphenyl)-4-methyl-1-propyl-1H-imidazole-5-carboxylate (7d).
29
30 Yellow oil (60.0 mg, 47%). 1H NMR (400 MHz, CDCl3): δ 7.27-7.31 (m, 1H),
31
32 7.01-7.03 (m, 2H), 6.92 (d, J = 8.4 Hz, 1H), 4.15-4.20 (m, 4H), 3.77 (s, 3H), 2.47 (s,
33
34 3H), 1.60-1.75 (m, 4H), 0.97 (t, J = 7.2 Hz, 3H), 0.71 (t, J = 7.6 Hz, 3H); 13C NMR
35
(100 MHz, CDCl3): δ 161.4, 159.2, 150.7, 147.9, 131.5, 129.6, 121.5, 119.1, 115.5,
36
37 114.6, 65.9, 55.4, 47.9, 24.8, 22.1, 16.2, 10.9, 10.7; IR (neat): ν (cm−1) 2965, 1679,
38
39 1472, 1414, 1268, 1168, 1119; HRMS (ESI-TOF) m/z: [M + H]+ Calcd for
40
41 C18H25N2O3 317.1860; Found: 317.1855.
42
43 Propyl 4-methyl-1-propyl-2-(pyridin-2-yl)-1H-imidazole-5-carboxylate (7e).
44
45 Colorless solid (43.0 mg, 37%): mp 44-46 oC. 1H NMR (400 MHz, CDCl3): δ 8.55 (d,
46
47 J = 4.4 Hz, 1H), 8.02 (d, J = 8.0 Hz, 1H), 7.67-7.71 (m, 1H), 7.18-7.21 (m, 1H), 4.79
48
49 (t, J = 7.6 Hz, 2H), 4.19 (t, J = 6.4 Hz, 2H), 2.47 (s, 3H), 1.69-1.75 (m, 4H), 0.97 (t, J
50
51
= 7.6 Hz, 3H), 0.78 (t, J = 7.6 Hz, 3H); 13C NMR (100 MHz, CDCl3): δ 161.3, 150.2,
52
148.6, 147.5, 147.1, 136.6, 124.5, 123.2, 120.5, 65.9, 48.0, 24.6, 22.1, 16.3, 10.9, 10.7;
53
54 IR (KBr): ν (cm−1) 2964, 1697, 1586, 1410, 1267, 1203, 1124; HRMS (ESI-TOF) m/z:
55
56 [M + H]+ Calcd for C16H22N3O2 288.1707; Found: 288.1700.
57
58 Propyl 4-methyl-1-propyl-2-vinyl-1H-imidazole-5-carboxylate (7f). Yellow oil
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3 (18.7 mg, 20%). 1H NMR (400 MHz, CDCl3): δ 6.52 (dd, J1 = 16.8 Hz, J2 = 11.2 Hz,
4
5 1H), 6.28 (d, J = 16.8 Hz, 1H), 5.49 (t, J = 11.2 Hz, 1H), 4.14-4.21 (m, 4H), 2.43 (s,
6
7 3H), 1.65-1.71 (m, 4H), 0.96 (t, J = 7.2 Hz, 3H), 0.85 (t, J = 7.6 Hz, 3H); 13C NMR
8
9 (100 MHz, CDCl3): δ 161.3, 148.0, 147.5, 122.1, 121.5, 118.7, 65.9, 46.3, 24.6, 22.1,
10
11 16.2, 11.0, 10.7; IR (neat): ν (cm−1) 2966, 1696, 1405, 1270, 1156, 1119, 759; HRMS
12
13 (ESI-TOF) m/z: [M + H]+ Calcd for C13H21N2O2 237.1598; Found: 237.1590.
14
15 (E)-propyl 2-(N-benzyl-4-methylphenylsulfonamido)-3-(benzylamino)
16
17 but-2-enoate (8a). Typical Procedure. To the solution of α-amino allene carboxylate
18
19
4g (242.9 mg, 0.63 mmol) in DMF (2 mL) was added amine 5g (135.0 mg, 1.26 mmol)
20 and the solution was stirred at room temperature. Upon reaction completion (1 h, TLC,
21
22 eluent: hexane-EtOAc, 1:1), the mixture was diluted with 50 mL EtOAc and washed
23
24 with brine, dried over Na2SO4, filtered and concentrated. The residue was purified by
25
26 column chromatography on silica gel with hexane/EtOAc (1:1~1:2, v:v) as the eluent
27
28 to get 8a (268.4 mg, 86%) as a colorless solid, mp 115-117 oC. 1H NMR (400 MHz,
29
30 CDCl3): δ 9.76 (br, 1H), 7.72 (d, J = 8.4 Hz, 2H), 7.23-7.32 (m, 10H), 7.06 (d, J = 7.2
31
32 Hz, 2H), 5.04 (d, J = 13.2 Hz, 1H), 4.29-4.32 (m, 2H), 4.09 (d, J = 13.2 Hz, 1H),
33
34 3.90-3.93 (m, 1H), 3.10-3.13 (m, 1H), 2.42 (s, 3H), 1.56 (s, 3H), 1.11-1.17 (m, 2H),
35
0.73 (t, J = 7.6 Hz, 3H); 13C NMR (125 MHz, CDCl3): δ 168.5, 168.2, 142.5, 138.3,
36
37 137.8, 136.3, 130.4, 129.1, 128.8, 128.2, 127.70, 127.68, 127.4, 126.6, 93.7, 64.5,
38
39 53.6, 47.2, 21.6, 21.4, 15.6, 10.6; IR (KBr): ν (cm−1) 2949, 1636, 1594, 1452, 1276,
40
41 1236, 1152, 1073; HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C28H33N2O4S
42
43 493.2156; Found: 493.2155.
44
45 (E)-propyl 2-(N-benzyl-4-methylphenylsulfonamido)-3-(isobutylamino)
46
47 but-2-enoate (8b). Colorless solid (217.4 mg, 79%): mp 80-82 oC. 1H NMR (400
48
49 MHz, CDCl3): δ 9.54 (br, 1H), 7.70 (d, J = 8.4 Hz, 2H), 7.25-7.31 (m, 7H), 5.02 (d, J
50
51
= 13.2 Hz, 1H), 4.06 (d, J = 13.2 Hz, 1H), 3.88-3.94 (m, 1H), 3.05-3.11 (m, 1H),
52
2.84-2.91 (m, 2H), 2.41 (s, 3H), 1.67-1.71 (m, 1H), 1.51 (s, 3H), 1.09-1.15 (m, 2H),
53
54 0.87 (t, J = 6.4 Hz, 6H), 0.73 (t, J = 7.2 Hz, 3H); 13C NMR (100 MHz, CDCl3): δ
55
56 168.5, 168.2, 142.4, 138.3, 136.5, 130.4, 129.0, 128.1, 127.6, 92.7, 64.3, 53.7, 51.1,
57
58 29.0, 21.6, 21.4, 20.0, 15.6, 10.6; IR (KBr): ν (cm−1) 2951, 1634, 1590, 1449, 1269,
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3 1155; HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C25H35N2O4S 459.2312; Found:
4
5 459.2311.
6
7 (E)-propyl 3-(benzylamino)-2-(4-methyl-N-propylphenylsulfonamido)
8
9 but-2-enoate (8c). Colorless solid (261.4 mg, 84%): mp 60-62 oC. 1H NMR (400
10
11 MHz, CDCl3): δ 9.81 (br, 1H), 7.65 (d, J = 8.4 Hz, 2H), 7.22-7.38 (m, 7H), 4.47-4.49
12
13 (m, 2H), 3.79-3.85 (m, 1H), 3.60-3.67 (m, 1H), 3.00-3.09 (m, 2H), 2.39 (s, 3H), 2.24
14
15 (s, 3H), 1.47-1.61 (m, 2H), 1.04-1.07 (m, 2H), 0.88 (t, J = 7.2 Hz, 3H), 0.66 (t, J = 7.2
16
17 Hz, 3H); 13C NMR (100 MHz, CDCl3): δ 168.7, 167.0, 142.3, 137.9, 137.7, 129.0,
18
128.9, 127.7, 127.6, 127.0, 95.0, 64.4, 52.3, 47.7, 22.0, 21.5, 21.4, 16.5, 11.4, 10.4; IR
19
20 (KBr): ν (cm−1) 2968, 1650, 1329, 1273, 1155, 662; HRMS (ESI-TOF) m/z: [M + H]+
21
22 Calcd for C24H33N2O4S 445.2156; Found: 445.2163.
23
24
25
26 ACKNOWLEDGMENT We are grateful to the National Natural Science Foundation
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28
29 of China (Project No. 21102029) and Zhejiang Provincial Natural Science Foundation
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31 of China (Project No. LY14B020013) for financial support.
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33
34
35
36 SUPPORTING INFORMATION 1H and 13C NMR spectra of all new compounds
37
38
39 and crystal structure and data of 6c, 7g and 8a. This material is available free of
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41
charge via the Internet at http://pubs.acs.org.
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43
44
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46
REFERENCES:
47
48
49 (1) (a) Grimmett, M. R. In Science of Synthesis; Neier, R., Ed.; Georg Thieme Verlag:
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Stuttgart, 2002; Vol. 12, pp 325-528. (b) Iinuma, Y.; Kozawa, S.; Ishiyama H.; Tsuda,
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26 Smith, T. W.; Zhao, M.; Yang, F.; Smith, D.; Cebe; P. Macromolecules, 2013, 46,
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31 (6) (a) Herrmann, W. A. Angew. Chem., Int. Ed. 2002, 41, 1290. (b) Gupta, S. K.;
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36 Abboud, K. A.; Aponick, A. J. Am. Chem. Soc., 2013, 135, 14548.
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39 (7) For examples, see: (a) Pusch, S.; Opatz, T. Org. Lett. 2014, 16, 5430. (b) Pooi, B.;
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Lee, J.; Choi, K.; Hirao, H.; Hong, S. H. J. Org. Chem. 2014, 79, 9231. (c) Yamauchi,
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44 T.; Shibahara, F.; Murai, T. J. Org. Chem. 2014, 79, 7185. (d) Chen, C.; Hu, W.; Yan,
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P.; Senadi, G. C.; Wang, J. Org. Lett. 2013, 15, 6116.
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49 (8) For recent reviews on the chemistry of allenamides, see: (a) Wei, L.-L.; Xiong, H.;
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Hsung, R. P. Acc. Chem. Res. 2003, 36, 773. (b) Lu, T.; Lu, Z.; Ma, Z.; Zhang, Y.;
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54 Hsung, R. P. Chem. Rev. 2013, 113, 4862.
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4 Lohse, A. G.; Hayashi, R.; Lu, Z.; Zhang, Y.; Hsung, R. P. Chem. Rev. 2010, 110, 5064.
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6 (b) Evano, G.; Coste, A.; Jouvin, K. Angew. Chem., Int. Ed. 2010, 49, 2840. (c) Evano,
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9 G.; Jouvin, K.; Coste, A. Synthesis 2013, 45, 17. (d) Wang, X.; Yeom, H.; Fang, L.; He,
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11 S.; Ma, Z.; Kedrowski, B. L.; Hsung, R. P. Acc. Chem. Res. 2014, 47, 560.
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14 (10) For examples on allenamides, see: (a) Lohse, A. G.; Hsung, R. P. Org. Lett. 2009,
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16 11, 3430. (b) Persson, A. K. Å.; Bäckvall, J. E. Angew. Chem., Int. Ed. 2010, 49, 4624.
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19 (c) Skucas, E.; Zbieg, J. R.; Krische, M. J. J. Am. Chem. Soc. 2009, 131, 5054. (d)
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21 Feltenberger, J. B.; Hsung, R. P. Org. Lett. 2011, 13, 3114. (e) Krenske, E. H.; He, S.;
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24 Huang, J.; Du, Y.; Houk, K. N.; Hsung, R. P. J. Am. Chem. Soc. 2013, 135, 5242.
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26 (11) For examples on ynamides, see: (a) Fadel, A.; Legrand, F.; Evano, G.; Rabasso, N.
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29 Adv. Synth. Catal. 2011, 353, 263. (b) Gati, W.; Rammah, M. M.; Rammah, M. B.;
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31 Couty, F.; Evano, G. J. Am. Chem. Soc. 2012, 134, 9078. (c) Gati, W.; Couty, F.;
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34 Boubaker, T.; Rammah, M. M.; Rammah, M. B.; Evano, G. Org. Lett. 2013, 15, 3122.
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36 (d) Brioche, J; Meyer, C.; Cossy, J. Org. Lett. 2013, 15, 1626. (e) Yao, P.-Y.; Zhang, Y.;
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39 Hsung, R. P.; Zhao, K. Org. Lett. 2008, 10, 4275.
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44 (13) Adler, P.; Gomes, F.; Fadel, A.; Rabasso, N. Eur. J. Org. Chem. 2013, 7546.
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49 2012, 10, 9556.
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(15) (a) Kong, Y.; Jiang, K.; Cao, J.; Fu, L.; Yu, L.; Lai, G.; Cui, Y.; Hu, Z.; Wang, G.
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54 Org. Lett. 2013, 15, 422. (b) Kong, Y.; Yu, L.; Fu, L.; Cao, J.; Lai, G.; Cui, Y.; Hu, Z.;
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Wang, G. Synthesis 2013, 45, 1975. (c) Kong, Y.; Yu, L.; Cui, Y.; Cao, J. Synthesis
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4 2014, 46, 183. (d) Yu, L.; Cao, J. Org. Biomol. Chem. 2014, 12, 3986. (e) Yu, L.;
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6 Deng, Y.; Cao, J. Synthesis 2015, 47, 783.
7
8
9 (16) CCDC 1043496.
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11 (17) 7a was transferred to corresponding ethyl ester with NaOEt/EtOH, and its 1H
12
13
14 NMR data was in accordance to reported data, see: Preti, L.; Attanasi, O. A.; Caselli,
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16 E.; Favi, G.; Ori, C.; Davoli, P.; Felluga, F.; Prati, F. Eur. J. Org. Chem. 2010, 4312.
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18
19 (18) CCDC 1043494.
20
21 (19) 1H NMR spectra of the crude reaction mixtures showed mixtures of Z/E (about
22
23
24 1:2) stereoisomers. The Z-isomer was converted to E-isomer spontaneously during the
25
26 course of flash chromatography on silica gel.
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29 (20) CCDC 1043495.
30
31 (21) Similar elimination reaction of 4-methylbenzenesulfinic acid was observed in
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33
34 ours previous work, see: Cao, J.; Xu, Y.; Kong, Y.; Cui, Y.; Hu, Z.; Wang, G.; Deng, Y.;
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36 Lai, G. Org. Lett. 2012, 14, 38.
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39 (22) (a) Cao, J.; Yang, X.; Hua, X.; Deng, Y.; Lai, G. Org. Lett. 2011, 13, 478. (b)
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Murarka, S.; Deb, I.; Zhang, C.; Seidel, D. J. Am. Chem. Soc. 2009, 131, 13226. (c)
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44 Barluenga, J.; Fananas-Mastral, M.; Aznar, F.; Valdes, C. Angew. Chem., Int. Ed. 2008,
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47, 6594. (d) Mori, K.; Kawasaki, T.; Sueoka, S.; Akiyama, T. Org. Lett. 2010, 12,
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49 1732.
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