HETEROCYCLES

Paper | Special issue | Vol. 77, No. 1, 2009, pp. 493-505
Received, 17th July, 2008, Accepted, 22nd August, 2008, Published online, 25th August, 2008.
DOI: 10.3987/COM-08-S(F)48

■ Synthesis of 6Z-Pandanamine by Regioselective Cyclization Reaction of 2-En-4-ynoic Acid Derivatives Promoted by Weak Base

Kou Hiroya,* Kazuya Takuma, Kiyofum Inamoto, and Takao Sakamoto

Graduate School of Pharmaceutical Science, Tohoku University, Aramaki, Aoba-ku, Sendai 980-8578, Japan

Abstract

The stereoselective synthesis of 6Z-pandanamine by base-promoted 5-exo-dig-selective cyclization reaction of bis-2-en-4-ynoic acid derivative as a key step is described.

INTRODUCTION
The intramolecular cyclization reaction by nucleophilic addition to the carbon−carbon triple bond is a useful methodology for constructing heterocyclic compounds, and significant efforts have been made to develop reagents that promote such reactions.1 We have previously reported effective methods for the synthesis of substituted heterocyclic compounds catalyzed by Cu(II) salts,2 Pd(PPh3)4-methyl propiolate complex,3 or PtCl4 in ethanol.4
We have also reported regiocontrolled intramolecular annulation reactions between carbon−carbon triple bonds and carboxylic acid, promoted by acid or base.5,6 Acid- and base-promoted cyclization gave isocoumarin 2 and phthalide 3, respectively, from carboxylic acid 1 (Figure 1). This method was also successfully applied to aliphatic (Z)-5-phenylpent-2-en-4-ynoic acid (4), which gave pyran-2(2H)-one 5 and furan-2(2H)-one 6, respectively. In this paper, we present the total synthesis of 6Z-pandanamine (11) using base-promoted cyclization as a key step.

In 2000, Takayama and co-workers reported the isolation of pandamarilactonine A (7) and B (8) (Figure 2) from the leaves of Pandanus amaryllifolius Roxb. from the Philippines, Thailand, and Indonesia, where it is used as a traditional medicine for toothache, heart problems and other conditions.7 Subsequently, pandamarilactonine C (9) and D (10), isomers of 7 and 8, respectively, were isolated from the plant,8 and the structure for the other congeners that contained 6E-pandanamine (12) were also determined.9 The biomimetic total synthesis of racemic 7 and 8 was reported by Takayama’s research group,7,8 and synthetic attempts at optically active forms were also reported.10 The first asymmetric total synthesis and determination of absolute configuration of 7 was achieved by Takayama and co-workers in 2005.11
6Z-Pandanamine (11) was isolated from the same plant in 2001,12 although the secondary amine 11 was a nameless precursor molecule for the total synthesis of 7 and 8 in 2000.7 Takayama reported that the optical purity of the isolated 7 was low (26% e.e.), and 8 was isolated as racemate. Later, Craik and co-workers suggested that both 7 and 8, which were not isolated using a solvent partitioned method, were artifacts formed during the acid-base extraction.9 Meanwhile, Takayama concluded that 7 was formed enzymatically with high optical purity and racemized during the isolation process, and that 8 was an artifact from 11, which were demonstrated by NMR experiments using 7 synthesized as an optically active form.11

RESULTS AND DISCUSSION
The synthetic strategy for 11 is shown in Figure 3. Briefly, the enol-lactone moieties of 11 are constructed from the symmetrical bis-carboxylic acid 13 by the base-promoted cyclization reaction. The stereochemistry of the enol moiety can be expected as “Z” from our previous results.5 Since 14, which is the precursor of the target natural product(s), has a symmetrical structure, it can be synthesized from the amide 15 and the iodide 16. Both 15 and 16 will be synthesized from the common intermediate 17, which will be synthesized by Pd-catalyzed coupling reaction between 4-hexyn-1-ol (18) and the vinyl iodide 19.

Along with the strategy shown above, we started synthesizing the common intermediate 17. The vinyl iodide 21 was selectively synthesized from propargyl alcohol (20) according to the literature,13 and it was converted to the TBDMS ether 22 by standard reaction conditions (Scheme 1). The Sonogashira coupling reaction between 22 and 18 was carried out in the presence of Pd(PPh3)4 and CuI in piperidine, which afforded the desired alcohol 23 in good yield. Treatment of 23 with N-tert-butoxycarbonyl-2- nitorobenzensulfonamide (24) under Mitsunobu reaction condition gave 25 in 95% yield.14 Attempts at selective removal of the Boc group of 25 using either Lewis acid or protonic acid were unsuccessful. However, the amide 26 was successfully obtained under thermal condition (diphenyl ether at 180 ˚C, 85%).15 On the other hand, the iodide 27 was synthesized from 23 by standard reaction conditions (I2, PPh3, imidazole, 92%).

As we could establish an efficient pathway to synthesize both fragments 26 and 27, the next task was the coupling reaction of them. The sodium salt of 26, which was prepared from 26 with NaH, was reacted with the iodide 27 in DMF at 80 ˚C, affording the desired alkylated product 28 in 90% yield. Next, 28 was converted to the bis-carboxylic acid 29, which is the substrate for the key reaction, by removal of the TBDMS group (TBAF) and oxidation of the allylic alcohol (Dess-Martin periodinane; DMP), followed by oxidation of the formyl group with NaClO2 in the presence of NaH2PO4･H2O (Pinnick oxidation). The cyclization reaction of the bis-carboxylic acid 29 was carried out by refluxing with the excess amount of DMAP in toluene to afford the expected bis-lactone 30 as a sole product, in 9% overall yield from 28. The stereochemistry of the cyclized product was determined as “Z” by comparing the chemical shift of the olefinic protons with those of 11 and 129,12 (Table 1). Consequently, 5-exo-dig reaction was far superior to 6-endo-dig mode in base-promoted cyclization reaction for this substrate, which is identical to our previous observation (Figure 1).5 We encountered trouble with the last stage, removal of the 2-nitorobenzensulfonamide (Ns) group. The lactone moiety decomposed before elimination of the Ns group due to instability of the vinylogous lactone, even under mild reaction condition [(A) PhSH, Cs2CO3, DMF, rt or (B) 2-mercaptoethanol, DBU, MeCN, rt] (Scheme 2).14

Having learned that the Ns group has to be removed before cyclization reaction, we decided to replace the protecting group before cyclization. Removal of the Ns group was carried out with ethanethiol and DBU in MeCN at room temperature, and the resulting secondary amine was treated with (Boc)2O in the presence of pyridine to afford the carbamate 31. The following three-step sequence was carried out as described above. Desilylation of 31 with TBAF, DMP oxidation, and Pinnick oxidation gave bis-2-en-4-ynoic acid derivative 32. Et3N was a much better base than DMAP for the stereoselective cyclization reaction of 32, and 33 was obtained as a single isomer in 37% overall yield from 28. The stereochemistry of 33 was confirmed as “Z” by comparing with 11 and 30 as described before (Table 1). The synthesis was completed by removal of the Boc group with formic acid in THF, which provided 11 (Scheme 3).

In summary, we demonstrated the application of base-promoted 5-exo-dig–selective cyclization reaction of bis-2-en-4-ynoic acid derivatives 29 and 32 to the enol-lactones 30 and 33. Although the bis-lactone 30 could not be converted to the target natural product, the synthesis of 6Z-pandanamine (11) was achieved from 33.

EXPERIMENTAL
(Z)-3-Iodo-2-methylprop-2-en-1-ol (21).13 Under Ar atmosphere, propargyl alcohol (20) (2.66 mL, 45.0 mmol) was added to a suspension of CuI (857 mg, 4.5 mmol) in anhydrous THF (50 mL) at 0 °C and stirred for 1 h, then a solution of MeMgBr (3.0 M solution in Et2O, 30 mL, 90 mmol) was added to a reaction mixture over 10 min and the stirring was continued for 90 min at the same temperature. A solution of I2 (17.1 g, 67.5 mmol) in anhydrous Et2O (80 mL) was added to a reaction mixture over 10 min, then stirred at rt for 90 min. The reaction mixture was treated with saturated aqueous NH4Cl solution and the aqueous solution was extracted with Et2O (40 mL x 3). The combined organic solution was washed with saturated aqueous NaCl solution, dried over anhydrous MgSO4, and the solvent was removed under reduced pressure. The residue was purified by silica gel column chromatography [hexane-AcOEt (3:1)] to afford 21 (7.27 g, 82%) as a yellow oil: IR (neat) cm-1 3329, 3053, 1435, 1013; 1H-NMR (400 MHz, CDCl3) δ 1.96 (3H, s), 3.40 (1H, br), 4.21 (2H, s), 5.96 (1H, s); 13C-NMR (100 MHz, CDCl3) δ 21.6, 67.8, 74.6, 145.9; MS m/z (relative intensity) 198 (100, M+), 149 (84), 71 (86); HRMS Calcd for C4H7IO: 197.9542. Found: 197.9536.

tert-Butyl-[(Z)-3-iodo-2-methylallyloxy]dimethylsilane (22). Imidazole (210 mg, 3.1 mmol), DMAP (12 mg, 0.15 mmol), and TBDMSCl (465 mg, 3.1 mmol) were added to a solution of (Z)-3-iodo-2-methylprop-2-en-1-ol (21) (309 mg, 1.5 mmol) in DMF (10 mL) and the mixture was allowed to react at rt for 25 min. The reaction mixture was extracted with Et2O (10 mL x 3). The combined organic solution was washed with saturated aqueous NaCl solution, dried over anhydrous MgSO4, and the solvent was removed under reduced pressure. The residue was purified by silica gel column chromatography [hexane-AcOEt (1:1)] to afford 22 (472 mg, 98%) as a colorless oil: IR (neat) cm-1 2955, 2930, 2856, 1472, 1097, 839; 1H-NMR (400 MHz, CDCl3) δ 0.10 (6H, s), 0.91 (9H, s), 1.91 (3H, s), 4.24 (2H, s), 5.85 (1H, s); 13C-NMR (100 MHz, CDCl3) δ −5.1, 18.3, 21.5, 25.9, 68.7, 72.4, 146.6; FAB-MS m/z 311 (M+). Anal. Calcd for C10H21IOSi: C, 38.46; H, 6.78. Found: C, 38.30; H, 6.60.

(Z)-8-(tert-Butyldimethylsilanyloxy)-7-methyloct-6-en-4-yn-1-ol (23). Under Ar atmosphere, CuI (10 mg, 0.05 mmol) and Pd(PPh3)4 (58 mg, 0.05 mmol) were added to a solution of tert-butyl-[(Z)-3-iodo-2-methylallyloxy]dimethylsilane (22) (312 mg, 1.0 mmol) in anhydrous piperidine (5 mL) and the mixture was stirred at 80 °C. After being stirred for 1 h, pentyn-1-ol (18) (138 mg, 1.5 mmol) was added to a reaction mixture and stirring was continued for 13 h. The reaction mixture was extracted with AcOEt (5 mL x 3). The combined organic solution was washed with saturated aqueous NaCl solution, dried over anhydrous MgSO4, and the solvent was removed under reduced pressure. The residue was subjected to silica gel column chromatography [hexane-AcOEt (9:1)] to afford 23 (207 mg, 77%) as a brown oil: IR (neat) cm-1 3354, 2953, 2930, 2856, 2361, 1251, 1074, 837; 1H-NMR (600 MHz, CDCl3) δ 0.09 (6H, s), 0.91 (9H, s), 1.79 (2H, quint, J = 6.6 Hz), 1.82 (3H, s), 2.46 (2H, td, J = 6.6, 2.2 Hz), 3.77 (2H, t, J = 6.6 Hz), 4.36 (2H, s), 5.28 (1H, brs); 13C-NMR (100 MHz, CDCl3) δ −5.2, 16.1, 18.3, 19.7, 25.9, 31.6, 61.6, 63.9, 77.6, 92.6, 105.5, 149.2; MS m/z: (relative intensity) 268 (4, M+), 211 (68), 183 (64), 75 (100); HRMS Calcd for C15H28O2Si: 268.1859. Found: 268.1844.

N-[(Z)-8-(tert-Butyldimethylsilanyloxy)-7-methyloct-6-en-4-ynyl]-N-(tert-butoxycarbonyl)-2-nitro-
benzenesulfonamide (25). Under Ar atmosphere, a solution of (Z)-8-(tert-butyldimethylsilanyloxy)- 7-methyloct-6-en-4-yn-1-ol (23) (1.34 g, 5.0 mmol) in anhydrous THF (5 mL) was added to a mixture of PPh3 (1.44 g, 5.5 mmol) and N-tert-butoxycarbonyl-2-nitrobenzenesulfonamide (24) (2.27 g, 7.5 mmol) in anhydrous THF (10 mL). Diethyl azodicarboxylate (40 w/v% toluene solution, 2.42 mL, 5.5 mmol) was added to a reaction mixture at 0 °C. After being stirred for 6 h, the reaction mixture was extracted with AcOEt (10 mL x 3). The combined organic solution was washed with saturated aqueous NaCl solution, dried over anhydrous MgSO4, and the solvent was removed under reduced pressure. The residue was purified by silica gel column chromatography [hexane-AcOEt (5:1)] to afford 25 (2.62 g, 95%) as a yellow oil: IR (neat) cm-1 2928, 2856, 2361, 1732, 1545, 1367, 1153; 1H-NMR (600 MHz, CDCl3) δ 0.09 (6H, s), 0.91 (9H, s), 1.37 (9H, s), 1.82 (3H, s), 1.99 (2H, quint, J = 7.2 Hz), 2.44 (2H, td, J = 7.2, 1.8 Hz), 3.86 (2H, t, J = 7.2 Hz), 4.38 (2H, s), 5.29 (1H, brs), 7.73-7.76 (3H, m), 8.30-8.32 (1H, m); 13C-NMR (100 MHz, CDCl3) δ −5.2, 17.2, 18.4, 19.8, 26.0, 27.4, 27.9, 29.5, 30.9, 47.4, 63.9, 77.7, 85.0, 91.9, 105.4, 124.2, 131.6, 133.2, 134.0, 149.4, 150.2; MS m/z (relative intensity) 552 (0.5, M+), 439 (24), 395 (46), 253 (64), 209 (100); HRMS Calcd for C26H40N2O7SSi: 552.2326. Found: 552.2323.

N-[(Z)-8-(tert-Butyldimethylsilanyloxy)-7-methyloct-6-en-4-ynyl]-2-nitrobenzenesulfonamide (26). A solution of N-[(Z)-8-(tert-butyldimethylsilanyloxy)-7-methyloct-6-en-4-ynyl]-N-(tert-butoxycarbonyl)- 2-nitrobenzenesulfonamide (25) (1.35 g, 2.45 mmol) in diphenyl ether (5 mL) was stirred at 180 °C for 20 min. The reaction mixture was subjected to silica gel column chromatography [hexane-AcOEt (3:1)] to afford 26 (937 mg, 85%) as a yellow oil: IR (neat) cm-1 3344, 2930, 2856, 2359, 1541, 1361, 1167, 1084; 1H-NMR (600 MHz, CDCl3) δ 0.06 (6H, s), 0.90 (9H, s), 1.77 (2H, quint, J = 6.6 Hz), 1.81 (3H, s), 2.40 (2H, td, J = 6.6, 2.0 Hz), 3.23 (2H, q, J = 6.6 Hz), 4.32 (2H, s), 5.24 (1H, brs), 5.40 (1H, t, J = 6.6 Hz), 7.73-7.76 (2H, m), 7.86-7.88 (1H, m), 8.14-8.15 (1H, m); 13C-NMR (100 MHz, CDCl3) δ −5.2, 16.8, 18.4, 19.8, 25.9, 28.8, 42.8, 63.9, 78.3, 91.2, 105.2, 125.3, 131.0, 132.7, 133.5, 133.6, 147.9, 149.7; MS m/z (relative intensity) 452 (0.7, M+), 395 (69), 209 (100); HRMS Calcd for C21H32N2O5SSi: 452.1801. Found: 452.1807.

tert-Butyl-[(Z)-8-iodo-2-methyloct-2-en-4-ynyloxy]dimethylsilane (27). Imidazole (544 mg, 8.0 mmol), PPh3 (1.57 g, 6.0 mmol), and I2 (1.52 g, 6.0 mmol) were successively added to a solution of (Z)-8-(tert-butyldimethylsilanyloxy)-7-methyloct-6-en-4-yn-1-ol (23) (1.08 g, 4.0 mmol) in CH2Cl2 (10 mL) at 0 °C. The reaction mixture was refluxed for 30 min and extracted with CHCl3 (10 mL x 3). The combined organic solution was washed with saturated aqueous NaCl solution, dried over anhydrous MgSO4, and the solvent was removed under reduced pressure. The residue was purified by silica gel column chromatography [hexane-AcOEt (9:1)] to afford 27 (1.39 g, 92%) as a yellow oil: IR (neat) cm-1 2955, 2928, 2856, 2360, 1252, 1086, 837; 1H-NMR (600 MHz, CDCl3) δ 0.09 (6H, s), 0.91 (9H, s), 1.82 (3H, s), 2.00 (2H, quint, J = 6.5 Hz), 2.48 (2H, td, J = 6.5, 2.2 Hz), 3.31 (2H, t, J = 6.5 Hz), 4.34 (2H, s), 5.28 (1H, brs); 13C-NMR (100 MHz, CDCl3) δ −5.1, 5.5, 18.4, 19.8, 20.6, 26.0, 32.3, 63.9, 78.3, 91.0, 105.3, 149.7; FAB-MS m/z 377 (M+−1).

N,N-Bis-[(Z)-8-(tert-butyldimethylsilanyloxy)-7-methyloct-6-en-4-ynyl]-2-nitrobenzenesulfonamide
(28). Under Ar atmosphere, a solution of N-[(Z)-8-(tert-butyldimethylsilanyloxy)-7-methyloct-6-en-4- ynyl]-2-nitrobenzenesulfonamide (26) (804 mg, 1.77 mmol) in anhydrous DMF (6 mL) was added to a suspension of NaH (85 mg, 2.12 mmol) in anhydrous THF (5 mL) at 0 °C. After being stirred for 1 h, a solution of tert-butyl-[(Z)-8-iodo-2-methyloct-2-en-4-ynyloxy]dimethylsilane (27) (1.34 g, 3.54 mmol) in anhydrous DMF (6 mL) was added to the reaction mixture. After being stirred for another 3 h at 80 °C, the reaction mixture was extracted with Et2O (30 mL x 3). The combined organic solution was washed with saturated aqueous NaCl solution, dried over anhydrous MgSO4, and the solvent was removed under reduced pressure. The residue was purified by silica gel column chromatography [hexane-AcOEt (9:1)] to afford 28 (1.12 g, 90%) as a brown oil: IR (neat) cm-1 2930, 2856, 1547, 1360, 1252, 1163, 1084, 837, 775; 1H-NMR (600 MHz, CDCl3) δ 0.07 (12H, s), 0.90 (18H, s), 1.79 (4H, quint, J = 7.2 Hz), 1.82 (6H, s), 2.33 (4H, td, J = 7.2, 1.8 Hz), 4.00 (4H, t, J = 7.2 Hz), 4.33 (4H, s), 5.25 (2H, s), 7.62 (1H, dd, J = 7.7, 1.8 Hz), 7.64-7.72 (2H, m), 8.03 (1H, dd, J = 7.7, 1.8 Hz); 13C-NMR (150 MHz, CDCl3) δ −5.2, 16.9, 18.3, 19.8, 25.9, 27.6, 46.8, 63.8, 78.0, 91.6, 105.3, 124.1, 130.9, 131.5, 133.2, 133.3, 147.9, 150.0; MS m/z (relative intensity) 702 (3, M+), 645 (68), 459 (100); HRMS Calcd for C36H58N2O6SSi2: 702.3554. Found: 702.3562.

N-Ns-Pandanamine (30). TBAF (1.0 M solution in THF, 11.4 mL, 11.4 mmol) was added to a solution of N,N-bis-[(Z)-8-(tert-butyldimethylsilanyloxy)-7-methyloct-6-en-4-ynyl]-2-nitrobenzenesulfonamide (28) (1.0 g, 1.43 mmol) in THF (5 mL) at rt. After being stirred for 20 min, the reaction mixture was extracted with AcOEt (10 mL x 3). The combined organic solution was washed with saturated aqueous NaCl solution, dried over anhydrous MgSO4, and the solvent was removed under reduced pressure to afford the crude alcohol, which was used to the next reaction without further purification.
Dess-Martin periodinane (DMP) (705 mg, 1.66 mmol) was added to a solution of the crude alcohol in CH2Cl2 (7 mL) at rt. After being stirred for 11 h, the reaction mixture was neutralized with saturated aqueous NaHCO3 solution and the aqueous solution was extracted with AcOEt (10 mL x 3). The combined organic solution was washed with saturated aqueous NaCl solution, dried over anhydrous MgSO4, and the solvent was removed under reduced pressure to afford the crude α,β-unsaturated aldehyde, which was used to the next reaction without further purification.
NaClO2 (360 mg, 3.32 mmol), NaH2PO4･H2O (518 mg, 3.32 mmol), and 2-methyl-2-butene (2 M solution in THF, 3.3 mL, 6.64 mmol) were added to a solution of the crude α,β-unsaturated aldehyde (156 mg) in a mixture of tert-BuOH-H2O (4:1, 5 mL) at rt. After being stirred for 30 min, 3N HCl was added and the aqueous solution was extracted with AcOEt (10 mL x 3) and the combined organic solution was washed with saturated aqueous NaCl solution, dried over anhydrous MgSO4, and the solvent was removed under reduced pressure to afford the crude carboxylic acid (29), which was used to the next reaction with out further purification.
DMAP (41 mg, 0.33 mmol) was added to a solution of the crude carboxylic acid (29) in toluene (5 mL) at 90 °C. After being stirred for 3.5 h, the reaction mixture was extracted with AcOEt (5 mL x 3). The combined organic solution was washed with saturated aqueous NaCl solution, dried over anhydrous MgSO4, and the solvent was removed under reduced pressure. The residue was purified by silica gel column chromatography [hexane-AcOEt (3:1)] to afford N-Ns-pandanamine (30) (65 mg, 9% overall yield from 28) as a brown oil: IR (neat) cm-1: 2926, 2855, 1767, 1543, 1346, 1161; 1H-NMR (600 MHz, CDCl3) δ 1.75 (4H, quint, J = 7.5 Hz), 2.00 (6H, s), 2.34 (4H, td, J = 7.8, 7.5 Hz), 3.31 (4H, t, J = 7.5 Hz), 5.15 (2H, t, J = 7.8 Hz), 7.00 (2H, s), 7.61 (1H, m), 7.69-7.70 (2H, m), 7.97-7.99 (1H, m); 13C-NMR (150 MHz, CDCl3) δ −0.02, 10.5, 23.3, 28.0, 29.7, 47.4, 112.2, 124.2, 129.5, 130.6, 131.7, 133.6, 137.7, 149.0, 170.9; MS m/z (relative intensity) 502 (29, M+), 180 (100); HRMS Calcd for C24H26N2O8S: 502.1410, Found: 502.1415.

N-Boc-Pandanamine (33). DBU (0.55 mL, 3.65 mmol) and EtSH (0.27 mL, 3.65 mmol) were added to a solution of N,N-bis[(Z)-8-(tert-butyldimethylsilanyloxy)-7-methyloct-6-en-4-ynyl]-2-nitrobenzenesulfon- amide (28) (512 mg, 0.73 mmol) in MeCN (5 mL) at rt. After being stirred for 1 h, the solvent was removed under reduced pressure to afford the crude amine, which was used to the next reaction without further purification.
Pyridine (0.29 mL, 3.65 mmol) and (Boc)2O (0.8 mg, 3.65 mmol) were added to a solution of the crude amine in MeOH (5 mL) at rt. After being stirred for 3 h, the reaction mixture was extracted with AcOEt (10 mL x 3). The combined organic solution was washed with saturated aqueous NaCl solution, dried over anhydrous MgSO4, and the solvent was removed under reduced pressure to afford the crude 31, which was used to the next reaction without further purification.
TBAF (1 M solution in THF, 3.65 mL, 3.65 mmol) was added to a solution of the crude 31 in THF (5
mL) at rt. After being stirred for 30 min, the reaction mixture was extracted with AcOEt (10 mL x 3). The combined organic solution was washed with saturated aqueous NaCl solution, dried over anhydrous MgSO4, and the solvent was removed under reduced pressure to afford the crude alcohol, which was used to the next reaction without further purification.
DMP (2.5 g, 5.84 mmol) was added to a solution of the crude alcohol in CH2Cl2 (8 mL) at rt. After being stirred for 7 h, the reaction mixture was neutralized with saturated aqueous NaHCO3 solution and the aqueous solution was extracted with AcOEt (10 mL x 3). The combined organic solution was washed with saturated aqueous NaCl solution, dried over anhydrous MgSO4, and the solvent was removed under reduced pressure to afford the crude α,β-unsaturated aldehyde, which was used to the next reaction without further purification.
NaClO2 (528 mg, 5.84 mmol), NaH2PO4･H2O (911 mg, 5.84 mmol), and 2-methyl-2-butene (2 M solution in THF, 5.8 mL, 11.7 mmol) were added to a solution of the crude α,β-unsaturated aldehyde in tert-BuOH-H2O (4:1, 5 mL) at rt. After being stirred for 3.5 h, 3N HCl was added and the aqueous solution was extracted with AcOEt (10 mL x 3). The combined organic solution was washed with saturated aqueous NaCl solution, dried over anhydrous MgSO4, and the solvent was removed under reduced pressure to afford the crude carboxylic acid 32, which was used to the next reaction without further purification.
Et3N (1.0 mL, 7.3 mmol) was added to a solution of the crude carboxylic acid 32 in toluene (5 mL) at 90 °C. After being stirred for 4.5 h, the reaction mixture was extracted with AcOEt (5 mL x 3). The combined organic solution was washed with saturated aqueous NaCl solution, dried over anhydrous MgSO4, and the solvent was removed under reduced pressure. The residue was chromatographed on silica gel [hexane-AcOEt (3:1)] to give N-Boc-pandanamine (33) (109 mg, 37% overall yield from 28) as a brown oil. Since 33 was decomposed on standing, the product was immediately used to the next reaction; 1H-NMR (400 MHz, CDCl3) δ 1.46 (9H, s), 1.70 (4H, t, J = 7.2 Hz), 2.00 (6H, s), 2.37 (4H, td, J = 7.5, 7.2 Hz), 3.20 (4H, brs), 5.16 (2H, brs), 6.99 (2H, s); MS m/z 317 (100).

6Z-Pandanamine (11). Formic acid (0.9 mL) was added to a solution of N-Boc-pandanamine (33) (2.4 mg, 0.06 mmol) in THF (0.3 mL) and stirred at rt for 12 h. The reaction mixture was neutralized with saturated aqueous NaHCO3 solution and the aqueous solution was extracted with CHCl3 (5 mL x 3). The combined organic solution was washed with saturated aqueous NaCl solution, dried over anhydrous MgSO4, and the solvent was removed under reduced pressure to afford 6Z-Pandanamine (11); 1H-NMR (600 MHz, CDCl3) δ 2.00 (6H, s), 2.00-2.06 (4H, m), 2.45 (4H, m), 2.85 (4H, m), 5.14 (2H, t, J = 7.8 Hz), 7.01 (2H, d, J = 1.8 Hz).

ACKNOWLEDGEMENTS
This work was partly supported by a Grant-in-Aid for Scientific Research (B) from Japan Society for the Promotion of Science (JSPS).

This paper is dedicated to Professor Emeritus Keiichiro Fukumoto at Tohoku University on the occasion of his 75th birthday.

References

1. Recent review, see: (a) N. T. Patil and Y. Yamamoto, Chem. Rev., 108, 3395. ; CrossRef (b) I. Larrosa, P. Romea, and F. Urpí, Tetrahedron, 2008, 64, 2683; CrossRef (c) F. Alonso, I. P. Beletskaya, and M. Yus, Chem. Rev., 2004, 104, 3079; CrossRef (d) G. Zeni and R. C. Larock, Chem. Rev., 2004, 104, 2285; CrossRef (e) I. Nakamura and Y. Yamamoto, Chem. Rev., 2004, 104, 2127; CrossRef (f) S. Doye, Synlett, 2004, 1653; CrossRef (g) F. Pohlki and S. Doye, Chem. Soc. Rev., 2003, 32, 104; CrossRef (h) T. Hosokawa, In Handbook of Organopalladium Chemistry for Organic Synthesis, ed. by E.-i. Negishi, A John Wiley & Sons, Inc.: New York, 2002; Vol. 2, p 2211-2244.
2. (a) K. Hiroya, S. Itoh, and T. Sakamoto, J. Org. Chem., 2004, 69, 1126; CrossRef (b) K. Hiroya, S. Itoh, M. Ozawa, Y. Kanamori, and T. Sakamoto, Tetrahedron Lett., 2002, 43, 1277; CrossRef (c) K. Hiroya, S. Itoh, and T. Sakamoto, Tetrahedron, 2005, 61, 10958. CrossRef
3. (a) K. Hiroya, S. Matsumoto, and T. Sakamoto, Org. Lett., 2004, 6, 2953 ; CrossRef (b) K. Hiroya, S. Matsumoto, M. Ashikawa, H. Kida, and T. Sakamoto, Tetrahedron, 2005, 61, 12330. CrossRef
4. K. Hiroya, S. Matsumoto, M. Ashikawa, K. Ogiwara, and T. Sakamoto, Org. Lett., 2006, 8, 5349. CrossRef
5. M. Uchiyama, H. Ozawa, K. Takuma, Y. Matsumoto, M. Yonehara, K. Hiroya, and T. Sakamoto, Org. Lett., 2006, 8, 5517. CrossRef
6. Recent related examples, see: (a) G. Le Bras, A. Hamze, S. Messaoudi, O. Provot, P.-B. Le Calvez, J.-D. Brion, and M. Alami, Synthesis, 2008, 1607; CrossRef (b) E. Marchal, P. Uriac, B. Legouin, L. Toupet, and P. van de Weghe, Tetrahedron, 2007, 63, 9979; CrossRef (c) L. Zhou and H.-F. Jiang, Tetrahedron Lett., 2007, 48, 8449; CrossRef (d) M. Terada, C. Kanazawa, and M. Yamanaka, Heterocycles, 2007, 74, 819; CrossRef (e) C. Kanazawa and M. Terada, Tetrahedron Lett., 2007, 48, 933; CrossRef (f) E. C. Woon, A. Dhami, M. F. Mahon, and M. D. Threadgill, Tetrahedron, 2006, 62, 4829; CrossRef (g) K. Cherry, J.-L. Parrain, J. Thibonnet, A. Duchêne, and M. Abarbri, J. Org. Chem., 2005, 70, 6669; CrossRef (h) V. Subramanian, V. R. Batchu, D. Barange, and M. Pal, J. Org. Chem., 2005, 70, 4778 and references cited therein. CrossRef
7. H. Takayama, T. Ichikawa, T. Kuwajima, M. Kitajima, H. Seki, N. Aimi, and M. G. Nonato, J. Am. Chem. Soc., 2000, 122, 8635. CrossRef
8. H. Takayama, T. Ichikawa, M. Kitajima, M. G. Nonato, and N. Aimi, Chem. Pharm. Bull., 2002, 50, 1303. CrossRef
9. A. A. Salim, M. J. Garson, and D. J. Craik, J. Nat. Prod., 2004, 67, 54. CrossRef
10. (a) P. Blanco, F. Busqué, P. de March, M. Figueredo, J. Font, and E. Sanfeliu, Eur. J. Org. Chem., 2004, 48; CrossRef (b) P. Blanco, P. de March, M. Figueredo, J. Font, and E. Sanfeliu, Tetrahedron Lett., 2002, 43, 5583. CrossRef
11. H. Takayama, R. Sudo, and M. Kitajima, Tetrahedron Lett., 2005, 46, 5795. CrossRef
12. H. Takayama, T. Ichikawa, M. Kitajima, N. Aimi, D. Lopez, and M. G. Nonato, Tetrahedron Lett., 2001, 42, 2995. CrossRef
13. (a) N. Hénaff and A. Whiting, Org. Lett., 1999, 1, 1137; CrossRef (b) J. G. Duboudin and B. Jousseaume, J. Organomet. Chem., 1979, 168, 1; CrossRef (c) J. G. Duboudin, B. Jousseaume, and A. Bonakdar, J. Organomet. Chem., 1979, 168, 227. CrossRef
14. T. Fukuyama, M. Cheung, and T. Kan, Synlett, 1999, 1301. CrossRef
15. (a) V. H. Rawal, R. J. Jones, and M. P. Cava, J. Org. Chem., 1987, 52, 19; CrossRef (b) H. H. Wasserman, G. D. Berger, and K. R. Cho, Tetrahedron Lett., 1982, 23, 465. CrossRef