Download PDF
Synlett 2012(3): 393-396  
DOI: 10.1055/s-0031-1290311
LETTER
© Georg Thieme Verlag Stuttgart ˙ New York

Rh(I)-Catalyzed Cyclocarbonylation of Enynes with Glyceraldehyde: An Available Carbonyl Source Derived from Sugar Alcohols

Keiichi Ikeda, Tsumoru Morimoto*, Takayuki Tsumagari, Hiroki Tanimoto, Yasuhiro Nishiyama, Kiyomi Kakiuchi
Graduate School of Materials Science, Nara Institute of Science and Technology (NAIST), Takayama, Ikoma, Nara 630-0192, Japan
Fax: +81(743)726081; e-Mail: morimoto@ms.naist.jp;

Further Information

Publication History

Received 20 October 2011
Publication Date:
19 January 2012 (online)

 PDF Download Permissions and Reprints All articles of this category

Abstract

Catalytic cyclocarbonylation reactions using a glyceraldehyde derivative as a carbonyl source are described. The rhodium(I)-catalyzed reaction of enynes with glyceraldehyde acetonide gave bicyclic cyclopentenones as the products. This presents an interesting use of a sugar alcohol derived carbon resource as well as a convenient procedure for the cyclocarbonylation of enynes.

Key words

rhodium - cyclocarbonylation - enyne - glyceraldehyde - sugar alcohol

The transition-metal-catalyzed cyclocarbonylation of enynes is an attractive research area, in that it provides easy access to the construction of bicyclic cyclopentenone frameworks from open-chain compounds. [¹] Because of its synthetic usefulness, considerable efforts have been focused on identifying an easy-to-handle carbonyl source that can be substituted for carbon monoxide in such reactions. Recent studies by us and others have demonstrated that formyl compounds, such as aldehydes [²] and a formate, [³] could be utilized as a carbonyl source using a strategy based on the catalytic decarbonylation of the formyl group. Quite recently, it was found that readily available carbon resources, including aldoses, can be used as a carbonyl source in such reactions. Chung et al. reported on rhodium(I)-catalyzed reactions of an enyne with d-glucose as a carbonyl source. [4] Independently, we reported on the use of aldose derivatives as a carbonyl source in cyclocarbonylation reactions. [5] We next targeted on the use of sugar alcohols or their derivatives as a new carbonyl source in the transformation. Sugar alcohols as well as carbohydrates represent readily available carbon resources that occur widely in nature. Chung’s report revealed that xylitol is also applicable as a carbonyl source through a dehydrogenation-decarbonylation sequence of the alcohol moiety in the presence of a catalyst. [4] Herein we report on the highly efficient cyclocarbonylation of enynes using glyceraldehyde acetonide, which is simply prepared from glycerol [6] and d-mannitol, as a carbonyl source. [7]

Racemic and chiral glyceraldehyde acetonide, rac- and (R)-1, were synthesized in two steps from glycerol [8] and d-mannitol, [9] respectively. We first examined the cyclocarbonylation of enyne 2a with rac-1. Under catalytic conditions consisting of 2.5 mol% of [RhCl(cod)]2 and 5 mol% of dppp [1,3-bis(diphenylphosphino)propane], the reaction of 2a with two equivalents of rac-1 in toluene at reflux resulted in the complete consumption of 2a in two hours to give the desired product 3a in 82% yield (Scheme  [¹] ). Chiral (R)-1 also reacted smoothly to afford the racemic product in high yield, however, the chirality of (R)-1 appeared to have no effect on the enantioselectivity during the synthesis of 3a. As a result, it was found that the multifunctionalized aldehyde 1, which is derived from a sugar alcohol, such as glycerol and d-mannitol, also can be utilized as an effective carbonyl source in the cyclocarbonylation of enynes. [¹0]

Scheme 1 Use of glyceraldehyde as a carbonyl source in cyclocarbonylation of enyne

Table 1 Rh(I)-Catalyzed Cyclocarbonylation Reactions of Various Enynes Using (R)-1 as a Carbonyl Source
Entry Enyne
 Conditionsa Time (h) Product
 Yield (%)b
 1
 2
 3

2a2b2c R = Ph
R = Bu
R = t-Bu 		A
A
B 		 2
 5
30

3a3b3c 87
82
73
 4
 5

2d2e R = Ph
R = Bu 		A
B 		 6
30

3d3e 87
61
 6

(E/Z = 93:7) 		2f B 22

3f 74
(single diastereomer)c
 7
 8
 9

2g2h2i R = Ph
R = Bu
R = Me 		A
B
A 		 5
 2
 4

3g3h3i 98
77
90
10
11
12
13

2j2k2l2m R = Ph
R = Bu
R = Me
R = H 		B
B
B
B 		40
36
17
 4

3j3k3l3m 87
93
93
69
14

2n B 24

3n 69
15

2o B 22

3o 44 (33)d
16

2p B 50

3p 26
17

2q B 22

3q 76
(cis/trans = 97:3)c
18

2r B  6

3r 58
(single diastereomer)c
19

2s B 48

3s 37
(single diastereomer)c
a Conditions A: enyne (0.5 mmol), (R)-1 (1 mmol), [RhCl(cod)]2 (0.0125 mmol), and dppp (0.025 mmol) in toluene (1 mL) at reflux under N2; conditions B: enyne (0.5 mmol), (R)-1 (1 mmol), [RhCl(cod)]2 (0.025 mmol), and dppp (0.05 mmol) in xylene (1 mL) at 130 ˚C under N2.
b Isolated yield.
c Diastereomeric ratios were determined by GC analysis.
d The value in parentheses is the yield of the recovered enyne.

Using (R)-1 as a carbonyl source, we examined the reactions of various enynes, which were different with respect to the substituents on the alkyne terminus and the alkene moiety, and the atom linking the two (Table  [¹] ). [¹¹] All the reactions of enynes were conducted in the presence of 2.5 mol% of [RhCl(cod)]2 and 5 mol% of dppp, in refluxing toluene (conditions A). In the case of reactions that did not proceed smoothly under these conditions, conditions B, 5 mol% of [RhCl(cod)]2, 10 mol% of dppp, and xylene at 130 ˚C were used. Alkyl-substituted O-linking enynes 2b and 2c also reacted with aldehyde (R)-1 to furnish the corresponding carbonyl compounds (Table  [¹] , entries 2 and 3). Reactions involving enynes 2d-f containing 1,1-di­substituted and 1,2-disubstituted alkene moieties proceeded smoothly to give the corresponding products 3d-f in moderate to high yields (Table  [¹] , entries 4-6). Enynes 2g-i, linked by tosylamide underwent cyclocarbonylation in excellent yields (Table  [¹] , entries 7-9). In most cases of C-linked enynes 2j-n, more severe conditions (B) were required to achieve the maximum yield (Table  [¹] , entries 10-14). Although the 1,7-enynes 2o and 2p were applicable to this transformation, the yields were low (Table  [¹] , entries 15 and 16). For substrates 2q-s where two groups, the alkyne and alkene units, were positioned on contiguous carbons of a ring system, the cyclocarbonylation proceeded diastereoselectively, resulting in the formation of tricyclic cyclopentenones 3q-s (Table  [¹] , entries 17-19). In general, reactions with aldehyde (R)-1 produced the desired carbonylated compounds not only in higher yields than those with acetylated aldose derivatives as a carbonyl source, [5] but in yields comparable to those with simple aldehydes. [²]

In the next series of experiments, the efficiency of the carbonyl transfer from the decarbonylation process to the cyclocarbonylation process was examined. The reaction of 2a with cyclohexylidene analogue 4 [¹²] under similar catalytic conditions in xylene at 130 ˚C gave the carbonylated product 3a in 82% yield, along with 135% of 5 (Scheme  [²] ). Based on the amount of the decarbonylated residue 5, the abstracted carbonyl moiety from aldehyde 4 was partially consumed in the cyclocarbonylation step. Thus, the decarbonylation of 4 proceeded catalytically, and independent of the cyclocarbonylation process, resulting in a partial release of free carbon monoxide. [²a]

Scheme 2 Efficiency of carbonyl-transfer from aldehyde 4 to 2a

Table 2 Asymmetric Cyclocarbonylation Reactions Using (R)-1 as a Carbonyl Sourcea

Entry Enyne 2 Time (h) Product 3 Yield (%)b ee (%)c
1 2a  2 3a 65 80 (S)
2 2b 18 3b 87 88 (S)
3 2g  3 3g 90 61 (S)
4 2h  4 3h 95 74 (S)
5 2j 22 3j 88 47 (R)
6 2k 24 3k 75 70 (R)
a The reaction was carried out with enyne (0.5 mmol), (R)-1 (1 mmol), [RhCl(cod)]2 (0.025 mmol), and dppp (0.05 mmol) at 130 ˚C under N2.
b Isolated yield.
c The ee and the absolute configuration were determined by HPLC ­using chiral stationary columns and specific optical rotation using a polarimeter, respectively.

We next examined the use of the sugar alcohol based aldehyde (R)-1 in the asymmetric cyclocarbonylation. As shown in Scheme  [¹] , the use of chiral (R)-1 did not result in an enantioselective transformation. The reaction of 2a with (R)-1 using (S)- and (R)-BINAP as a ligand, instead of dppp, was then carried out to give the carbonylated product 3a in lower yield and lower enantioselectivity: 46% yield [50% ee (S)] and 54% yield [46% ee (R)], respectively. From the results of screening various ligands and solvents, the use of (S)-tolBINAP as a ligand in the solvent-free system afforded the best results from the viewpoints of chemical yield and enantioselectivity. [²b] [c] The results are summarized in Table  [²] . The asymmetric conditions led to the formation of high yields of the carbonylated products with moderate to high enantioselectivities. When enyne 2a (0.5 mmol) was reacted with (R)-1 (1.0 mmol) in the presence of [RhCl(cod)]2 (0.0125 mmol) and (S)-tolBINAP (0.025 mmol) at 130 ˚C, 2a was completely consumed within two hours to give the carbonylated product 3a in 65% with 80% ee (S; Table  [²] , entry 1). [¹³] The use of rac-1 instead of (R)-1 afforded similar results: 70% yield and 79% ee. The reaction of enyne 2b in which the phenyl group in 2a is replaced with a butyl group also resulted in the formation of the carbonylated product 3b in higher yield and ee (Table  [²] , entry 2). Similar tendencies were observed in the reactions of other enynes 2g,h,j,k, which are linked by nitrogen and carbon atoms (Table  [²] , entries 3-6).

Finally, we investigated the effect of the chirality of ­tolBINAP on the efficiency of the reaction under the above asymmetric catalytic conditions using (R)-1. There was no difference in isolated chemical yields and ee values between the reactions using (S)- or (R)-tolBINAP (65% yield, 80%ee; Scheme  [³] ). At an early stage of each reaction, at which point the carbonylation is linearly dependent on the reaction time, the rate of formation of the product 3a is slightly, but clearly, different: the turnover frequency (TOF) is 5.20˙10-¹ h-¹ for (S)-tolBINAP compared with 3.23˙10-¹ h-¹ for (R)-tolBINAP (Figure  [¹] ). Thus, these results would issue from the diastereotopic combination of the chirality of (R)-1 with that of the ligand, S or R, thus implying that the rate-determining step of the reaction is involved in the decarbonylation process of the aldehyde.

Scheme 3 Asymmetric reaction of 2a using (S)- and (R)-tolBINAP

Figure 1 Profile of asymmetric reaction of 2a with (R)-1

In conclusion, we report here on the use of a sugar alcohol derived aldehyde as a carbonyl source in the cyclocarbonylation of enynes. The racemic and chiral sugar alcohol derived aldehydes used in this study are readily prepared in two steps from glycerol and d-mannitol, respectively. Various enynes can be carbonylated using these derivatives. The present study provides a demonstration showing that such carbonyl sources can be conveniently used in the cyclocarbonylation of enynes.

Supporting Information for this article is available online at http://www.thieme-connect.com.accesdistant.sorbonne-universite.fr/ejournals/toc/synlett.

Acknowledgment

This work was financially supported, in part, by a Grant-in-Aid for Scientific Research on Innovative Area ‘Molecular Activation ­Directed toward Straightforward Synthesis’ from MEXT. T.M. ac­knowledges the grant for Mitsui Chemicals Inc. Award in Synthetic Organic Chemistry to the Society of Synthetic Organic Chemistry, Japan. We also thank Ms. Mika Yamamura and Ms. Yuriko ­Nishiyama for assistance in obtaining HRMS.

10

Under identical reaction conditions, the use of glycerol itself as a carbonyl source gave 3a only in 11% yield, along with 13% of the hydrogen adduct of 2a and 30% of a mixture of dimers of 2a.

11

Typical Procedure for the Rhodium-Catalyzed Cyclocarbonylation Reaction of Enyne 2a with Glyceraldehyde Acetonide ( R )-1 (Conditions A) To a suspension of [RhCl(cod)]2 (6.16 mg, 0.0125 mmol), dppp (10.63 mg, 0.025 mmol), and (R)-1 (131.0 mg, 1.0 mmol) in anhyd toluene (1 mL) was added enyne 2a (86.1 mg, 0.5 mmol) under N2. After degassing the mixture through three freeze-pump-thaw cycles, the solution was stirred at reflux for an appropriate time. The reaction mixture was evaporated under reduced pressure. The residue was purified by column chromatography on silica gel with hexane-EtOAc (v/v = 2:1) as the eluent.
Compound 3a
Yield: 87%; colorless oil; R f = 0.31 (hexane-EtOAc, 2:1). ¹H NMR (500 MHz, CDCl3): δ = 2.31 (dd, J = 17.5, 2.4 Hz, 1 H), 2.82 (dd, J = 17.5, 6.4 Hz, 1 H), 3.27-3.32 (m, 1 H), 3.19-3.23 (m, 1 H), 4.35 (t, J = 7.6 Hz, 1 H), 4.56 (d, J = 16.2 Hz, 1 H), 4.91 (d, J = 16.2 Hz, 1 H), 7.33-7.38 (m, 3 H), 7.49 (d, J = 6.7 Hz, 2 H). ¹³C NMR (125 MHz, CDCl3): δ = 40.3, 43.2, 66.2, 71.3, 128.0, 128.5, 128.6, 130.5, 134.6, 177.4, 206.8.²a

13

Using a combination of [IrCl(cod)]2 and (S)-tolBINAP, the reaction of 2a with (R)-1 in 1,4-dioxane at 120 ˚C resulted in the more enantioselective formation of (S)-3a (89% ee), although the chemical yield was much lower (31%).

10

Under identical reaction conditions, the use of glycerol itself as a carbonyl source gave 3a only in 11% yield, along with 13% of the hydrogen adduct of 2a and 30% of a mixture of dimers of 2a.

11

Typical Procedure for the Rhodium-Catalyzed Cyclocarbonylation Reaction of Enyne 2a with Glyceraldehyde Acetonide ( R )-1 (Conditions A) To a suspension of [RhCl(cod)]2 (6.16 mg, 0.0125 mmol), dppp (10.63 mg, 0.025 mmol), and (R)-1 (131.0 mg, 1.0 mmol) in anhyd toluene (1 mL) was added enyne 2a (86.1 mg, 0.5 mmol) under N2. After degassing the mixture through three freeze-pump-thaw cycles, the solution was stirred at reflux for an appropriate time. The reaction mixture was evaporated under reduced pressure. The residue was purified by column chromatography on silica gel with hexane-EtOAc (v/v = 2:1) as the eluent.
Compound 3a
Yield: 87%; colorless oil; R f = 0.31 (hexane-EtOAc, 2:1). ¹H NMR (500 MHz, CDCl3): δ = 2.31 (dd, J = 17.5, 2.4 Hz, 1 H), 2.82 (dd, J = 17.5, 6.4 Hz, 1 H), 3.27-3.32 (m, 1 H), 3.19-3.23 (m, 1 H), 4.35 (t, J = 7.6 Hz, 1 H), 4.56 (d, J = 16.2 Hz, 1 H), 4.91 (d, J = 16.2 Hz, 1 H), 7.33-7.38 (m, 3 H), 7.49 (d, J = 6.7 Hz, 2 H). ¹³C NMR (125 MHz, CDCl3): δ = 40.3, 43.2, 66.2, 71.3, 128.0, 128.5, 128.6, 130.5, 134.6, 177.4, 206.8.²a

13

Using a combination of [IrCl(cod)]2 and (S)-tolBINAP, the reaction of 2a with (R)-1 in 1,4-dioxane at 120 ˚C resulted in the more enantioselective formation of (S)-3a (89% ee), although the chemical yield was much lower (31%).

   Permissions and Reprints All articles of this category

Scheme 1 Use of glyceraldehyde as a carbonyl source in cyclocarbonylation of enyne

Scheme 2 Efficiency of carbonyl-transfer from aldehyde 4 to 2a

Scheme 3 Asymmetric reaction of 2a using (S)- and (R)-tolBINAP

Figure 1 Profile of asymmetric reaction of 2a with (R)-1