Stereocontrol in Radical Processes through the Exocyclic Effect:

Dual Role of Triethylboron as Radical Initiator and In Situ

Derivatization Agent
Jean-Pierre Bouvier, Grace Jung, Ziping Liu, Brigitte Guérin, and Yvan Guindon*
Institut de recherches cliniques de Montréal(IRCM), Bio-organic Chemistry Laboratory, 110
avenue des Pins Ouest, Montréal QC, Canada H2W 1R7;
Department of Chemistry and Department of Pharmacology, Université de Montréal,
Montréal QC, Canada H3C 3J7;

SUPPORTING INFORMATION
TABLE OF CONTENTS

A. Experimental procedures and characterization data for compounds 1, 10-12, 13 and

14, boronates 2’ and 3’ (derivatives of 2 and 3, respectively), and lactone 1’

(derivatized from 1).

B. Determination of relative configuration for compounds 1-3, 11, and 12.

C. NMR spectra for compounds 2, 3, 11, 12, 2’ and 3’ and lactone 1’; X-ray structure of
lactone 19.

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A. Experimental procedures and characterization data for compounds 1-3, 10-12,

13 and 14, boronates 2’ and 3’, and lactone 1’.

General Methods. All reactions requiring anhydrous conditions were conducted

under a positive nitrogen atmosphere in oven-dried glassware using standard syringe

techniques. The anhydrous solvents were purchased from Aldrich and used as received. i-

Pr2NH and Et3N were freshly distilled from CaH2 under N2 atmosphere. n-Butyllithium

(1.6 M solution in hexane) was purchased from Aldrich and titrated prior to use

(diphenylacetic acid end-point in dry THF). Tributyltin hydride, triethylborane (1 M

solution in hexane), t-butyl 2-bromoacetate, and 2,2-dimethoxypropane were also

purchased from Aldrich and used as received. 1,1,2-trimethoxyethane and 1,1,3-

trimethoxypropane were purchased from Aldrich and distilled prior to use. Flash

chromatography was performed on Merck silica gel 60 (0.040-0.063 mm) using nitrogen

pressure. Analytical thin-layer chromatography (TLC) was carried out on precoated (0.25

mm) Merck silica gel F-254 plates. Melting points were determined on an electrothermal

melting point apparatus and are uncorrected.

The preparation and characterization data of 4-9 have been reported previously.1

Compound 1: To a 0.1 M solution of tert-butyl 2-phenylselenopropionate2 in THF at

0 °C were successively added TBAF (5 equiv) and acetic acid (2 equiv). After being

allowed to warm to room temperature, the reaction mixture was stirred until all of the

substrate was consumed (2 h). The reaction mixture was diluted with EtOAc, quenched

(1) Guindon, Y.; Yoakim, C.; Gorys, V.; Ogilvie, W.W.; Delorme, D.; Renaud, J.; Robinson, G.; Lavallée, J.-
F.; Slassi, A.; Jung, G.; Rancourt, J.; Durkin, K.; Liotta, D. J. Org. Chem. 1994, 59, 1166
(2) Guindon, Y.; Faucher, A.-M.; Bourque, É.; Caron, V.; Jung, G.; Landry, S. R. J. Org. Chem. 1997, 62,
9276.

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with a phosphate buffer (pH 7.2) solution, and then extracted twice with EtOAc. The

combined organic extracts were washed with a saturated aqueous solution of NaHCO3 and

brine, dried with MgSO4, filtered, and concentrated under reduced pressure. The crude oil

was purified by flash column chromatography to afford 1 as a white solid (81%): mp 70-71

°C, Rf 0.12 (hexanes-EtOAC, 6:4); IR (neat) υmax 3550, 3500, 1720 cm-1; MS (FAB) 360

(19, MH), 287 (49), 230 (28), 157 (19), 57 (100); 1H NMR (400 MHz, CDCl3) δ 1.35 (s,

3H), 1.46 (s, 9H), 1.68-1.77 (m, 1H), 2.09-2.13 (m, 1H), 2.50 (dd, J = 7.2, 3.6 Hz, 1H),

3.37 (d, J = 5.2 Hz, 1H), 3.81-3.88 (m, 2H), 4.03-4.08 (m, 1H), 7.32 (t, J = 7.2 Hz, 2H),

7.40 (t, J = 7.2 Hz, 1H), 7.60 (d, J = 6.8 Hz, 2H); 13C NMR (50 MHz, CDCl3) δ 18.8, 28.0,

33.3, 54.5, 61.9, 75.6, 82.4, 126.5, 128.8, 129.4, 138.1, 173.1; HRMS (FAB) calcd for

C16H25O480Se: 361.0918, found: 361.0933 (-4.2 ppm). Anal. calcd for C16H24O4Se: C

53.48, H 6.73; found: C 53.29, H 6.81.

Compound 10: To a cold (0 °C) stirred solution of iPr2NH (1.3 equiv) in THF under

a N2 atmosphere was added a solution of n-butyllithium (1.2 equiv) in hexanes. The

resultant mixture was stirred for 30 min and then cooled to -78 °C before tert-butyl 2-

phenylselenopropionate2 (9.4 g, 33 mmol) in THF was added. After the reaction mixture

was stirred at -78 °C for 30 min, 3-(N-tert-butoxycarbonyl-N-ethylamino)-1-propanal3 (6.0

g, 30 mmol) was added, and the resultant solution was stirred at -78 °C until all of the

substrate was consumed (4 h). The cold bath was removed, and the reaction mixture was

quenched with a saturated aq NH4Cl. The mixture was then extracted successively with

Et2O (1X) and CH2Cl2 (2X), dried with anhydrous MgSO4, filtered, and concentrated under

(3) Chaubet, F.; Nguyen Van Duong, M.; Courtieu, J.; Gaudemer, A. Can. J. Chem. 1991, 69, 1107.

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reduced pressure. Purification of the crude material by flash column chromatography

(CH2Cl2:EtOAc, 10:1) afforded two diastereomers (12.0 g, 82%). To a solution of the less

polar syn isomer (Rf 0.33; CH2Cl2-EtOAc, 10:1) in CH2Cl2 was added a solution of 4M

HCl in dioxane (4 equiv) at room temperature. The mixture was stirred until the starting

material was no longer evident by TLC (1h). After concentration of the solvent, the residue

was dissolved in water and extracted twice with ether. The cold (0 °C) aqueous solution

was treated with a 1M aq solution of NaOH until a neutral pH was achieved and the

resultant solution was extracted thrice with CH2Cl2. The combined CH2Cl2 extracts were

washed with brine and dried with Na2SO4. Removal of the solvent gave the desired amino

ester 10 (syn) as a yellow oil: Rf 0.19 (CH2Cl2-MeOH, 30:1; Al2O3); IR (neat) υmax 1705

cm-1; MS (FAB) 388 (100, MH), 386 (52), 332 (21), 230 (7), 174 (16); 1H NMR (400

MHz, CDCl3) δ 1.10 (t, J = 7.3 Hz, 3H), 1.35 (s, 9H), 1.43 (s, 3H), 1.45-1.52 (m, 1H), 1.57-

1.68 (m, 1H), 2.62 (dq, J = 11.4, 7.0 Hz, 1H), 2.71 (dq, J = 11.4, 7.0 Hz, 1H), 2.76 (ddd, J

= 12.4, 10.8, 3.6 Hz, 1H), 2.97 (td, J = 12.1, 4.1 Hz, 1H), 4.15 (dd, J = 10.2, 1.9 Hz, 1H),

7.26-7.37 (m, 5H); 13C NMR (100 MHz, CDCl3) δ 15.1, 17.3, 27.8, 28.2, 30.2, 43.7, 48.6,

56.3, 75.0, 81.0, 127.3, 128.5, 128.9, 138.1, 138.2, 171.9; HRMS (FAB) calcd for

C18H30O3N80Se: 388.1391, found: 388.1375 (+4.1 ppm). Anal. calcd for C18H29O3NSe: C

55.95, H 7.57, N 3.62; found: C 55.94, H 7.59, N 3.67.

General procedure for reduction with in situ derivatization or Lewis acid: To a

solution of 1 in CH2Cl2 (0.1 M) at room temperature was added either Et3B (1.3 equiv)/air,

DIEA (1.8 equiv)/Bu2BOTf (1.3 equiv), or DIEA (2.2 equiv)/Me2SiCl2 (1.8 equiv). The

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resultant mixture was stirred for 1-2 h, cooled to 0 oC, and subjected to reduction as

described below.

General procedure for radical reduction in the absence of Lewis acid: To a

cooled (0 oC) stirred solution of 1 in CH2Cl2 (0.1 M) were added Bu3SnH (2 equiv) and

either Et3B (0.2 equiv) or AIBN (0.2 equiv; initiation by sunlamp irradiation). The

resultant solution was stirred for 1-2 h, after which 0.2 equiv of Et3B was added every 30

min until all of the substrate was consumed. 1,3-Dinitrobenzene (0.2 equiv) was then

added, and the resultant mixture was stirred at 0 oC for 15 min before being allowed to

warm to room temperature. After concentration under reduced pressure, the crude residue

was analyzed by 1H NMR to determine the anti:syn ratio. The crude mixture of anti and

syn products was derivatized as boronates, for which ratios were determined by 1H NMR

and GC. The boronate mixture was then treated with silica gel and MeOH (25 mL) to

regenerate the diol products, which were separated by flash column chromatography.

Compound 2: colorless oil; Rf 0.12 (hexanes-EtOAc, 1:1); IR (neat) υmax 3400, 1715

cm-1; MS (FAB) 205 (10, MH), 149 (76), 131 (52), 89(9); 1H NMR (400 MHz, CDCl3) δ:

1.18 (d, J = 6.8 Hz, 3H), 1.47 (s, 9H), 1.69-1.76 (m, 2H), 2.44 (quint, J = 7.2 Hz, 1H), 2.63

(dd, J = 6.0, 4.8 Hz, 1H), 3.42 (d, J = 5.6 Hz, 1H), 3.84-3.91 (m, 3H); 13C NMR (100 MHz,

CDCl3) δ: 14.2, 28.1, 36.0, 46.1, 61.5, 73.7, 81.4, 175.4 ; HRMS (FAB) calcd for

C10H21O4: 205.1440, found: 205.1446. (-3.0 ppm).

Compound 3: white solid; mp 48-49 °C, Rf 0.12 (hexanes-EtOAc, 1:1); IR (CDCl3)

υmax 3400, 1715 cm-1; MS (FAB) m/z 205 (21, MH+), 149 (100), 131 (66), 113 (19), 77

(16); 1H NMR (400 MHz, CDCl3) δ: 1.17 (d, J = 7.2 Hz, 3H), 1.46 (s, 9H), 1.53-1.60 (m,

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1H), 1.72-1.81 (m, 1H), 2.43 (qd, J = 7.2, 4.0 Hz, 1H), 2.55 (t, J = 5.2 Hz, 1H), 3.29 (d, J =

3.6 Hz, 1H), 3.85 (q, J = 4.8 Hz, 2H), 4.07-4.12 (m, 1H); 13C NMR (100 MHz, CDCl3) δ:

11.4, 28.0, 35.3, 45.4, 61.5, 71.8, 81.2, 175.4; HRMS (FAB) calcd for C10H21O4: 205.1440,

found: 205.1448 (-4.0 ppm).

Compounds 11 (anti) and 12 (syn) were obtained from the radical reduction of

phenylselenoester 10. After the anti:syn ratio of the crude reduced products was

determined by 1H NMR, the mixture was treated with di-tert-butyl dicarbonate (2.1 equiv)

in THF (0.02M) for 12 h at room temperature. After concentration, the residue was

purified by flash chromatography to afford a mixture of N-Boc derivatives as a colorless

oil: Rf 0.21 (hexanes-EtOAc, 8:2); MS (FAB) 332 (51, MH), 298 (8), 232 (62), 176 (100);

1
H NMR (400 MHz, CDCl3, 3:1 mixture of diastereomers) δ 1.10 (t, J = 7.2 Hz, 3H), 1.17

(d, J = 7.2 Hz, 3H), 1.44 (s, 9H), 1.45 (s, 9H), 1.58-1.68 (m, 2H), 2.33-2.42 (m, 1H), 2.98-
13
3.17 (m, 2H), 3.21-3.30 (m, 1H), 3.63-3.73 (m, 1H), 4.08-4.14 (m, 1H); C NMR (100

MHz, CDCl3, 3:1 mixture of diastereomers) δ 12.7, 13.7, 28.1, 28.5, 29.1, 33.2, 42.2, 43.3,

46.0, 69.0, 79.7, 80.5, 156.4, 175.1; HRMS (FAB) calcd for C17H34O5N: 332.2437, found:

332.2427 (3.1 ppm).

Compound 13 was isolated as a yellow oil: Rf 0.53 (hexanes-EtOAc, 1:1); IR (neat)

υmax 1725 cm-1; MS (FAB) 398 (45, MH), 343 (90), 297 (37), 241 (91), 133 (100); 1H

NMR (400 MHz, CDCl3) δ 0.62 (q, J = 7.6 Hz, 2H), 0.81 (t, J = 7.6 Hz, 3H), 1.36 (s, 3H),

1.39 (s, 9H), 1.82 (qd, J = 12.4, 5.2 Hz, 1H), 2.34 (dd, J = 13.6, 2.0 Hz, 1H), 3.97 (td, J =

12.4, 2.8 Hz, 1H), 4.06-4.10 (m, 1H), 4.43 (dd, J = 11.6, 2.8 Hz, 1H), 7.30 (t, J = 7.2, 2H),

7.39 (t, J = 7.6 Hz, 1H), 7.60 (d, J = 8.0 Hz, 2H); 13C NMR (100 MHz, CDCl3) δ 7.6, 16.6,

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27.6, 27.8, 53.0, 61.8, 74.4, 81.2, 126.5, 128.8, 129.3, 138.0, 171.6; 11B NMR (400 MHz,

CDCl3) δ 31 ppm; HRMS (EI) calcd for C18H27O411B80Se: 398.1168, found: 398.1157 (2.7

ppm). Anal. calcd for C18H27O4BSe: C 54.48, H 6.85; found: C 54.58, H 7.20.

Compound 14 was isolated as a yellow oil: Rf 0.74 (hexanes-EtOAc, 1:1); IR (neat)

υmax 1730 cm-1; MS (FAB) 426 (MH, 11), 371 (22), 241 (29), 167 (19), 57 (100); 1H NMR

(400 MHz, CDCl3) δ 0.63 (t, J = 6.4 Hz, 2H), 0.82 (t, J = 7.2 Hz, 3H), 0.88-1.34 (m, 1H),

1.35 (s, 3H), 1.38 (s, 9H), 1.76-1.87 (m, 1H), 2.34 (dd, J = 14.0, 1.6 Hz, 1H), 3.96 (td, J =

12.4, 2.8 Hz, 1H), 4.06-4.10 (m, 1H), 4.43 (dd, J = 11.6, 2.4 Hz, 1H), 7.30 (t, J = 6.8, 2H),

7.39 (t, J = 7.2 Hz, 1H), 7.56 (d, J = 8.0 Hz, 2H); 13
C NMR (100 MHz, CDCl3) δ 13.9,
11
16.7, 25.3, 26.2, 27.7, 27.8, 53.1, 61.8, 74.4, 81.2, 126.5, 128.8, 129.3, 138.0, 171.6; B

NMR (400 MHz, CDCl3) δ 31 ppm; HRMS (FAB) calcd for C20H31O411B80Se: 426.1481,

found: 426.1462 (+4.4 ppm). Anal. calcd for C20H31O4BSe: C 56.49, H 7.35; found: C

56.77, H 7.65.

Ethylboronate 2’ (anti) was prepared from reduced product 2 (anti) and isolated as a

colorless oil. Capillary GC analyses were performed on a Hewlett Packard 6890 instrument

using a 0.25 mm × 30 m SE-30 column. GC tR 7.77 min (tinj. 280 °C, tFID 280 °C, split

method, 83:1, 0.5 mL/min, program 150 °C/8min, 20 °C/min, 280/ 5min). Rf 0.58

(hexanes-EtOAc, 40:60); IR (neat) υmax 1735 cm-1; 1H NMR (400 MHz, CDCl3) δ 0.65 (q,

J = 7.8 Hz, 2H), 0.85 (t, J = 7.8 Hz, 3H), 1.08 (d, J = 7.1 Hz, 3H), 1.46 (s, 9H), 1.63-1.75

(m, 1H), 1.90 (qd, J = 11.0, 2.9 Hz, 1H), 2.45 (quint, J = 7.1 Hz, 1H), 3.92 (td, J = 11.1, 3.1

Hz, 1H), 3.99-4.04 (m, 1H), 4.07-4.12 (m, 1H); 13C NMR (100 MHz, CDCl3) δ 7.7, 12.5,

28.1, 29.3, 47.0, 61.0, 72.7, 173.9.

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 Ethylboronate 3’ (syn) was prepared from reduced product 3 (syn) and isolated as a

colorless oil. GC tR 7.40 min (tinj. 280 °C, tFID 280 °C, split method, 83:1, 0.5 mL/min,

program 150 °C/8min, 20 °C/min, 280/ 5min). Rf 0.58 (hexanes-EtOAc, 40:60); IR (neat)

υmax 1730 cm-1; 1H NMR (400 MHz, CDCl3) δ 0.66 (q, J = 7.9 Hz, 2H), 0.86 (t, J = 7.9 Hz,

3H), 1.22 (d, J = 7.0 Hz, 3H), 1.45 (s, 9H), 1.74-1.82 (m, 1H), 1.90 (qd, J = 10.8, 3.2 Hz,

1H), 2.40 (quint, J = 7.1 Hz, 1H), 3.93 (td, J = 11.0, 3.3 Hz, 1H), 3.99-4.07 (m, 2H); 13C

NMR (100 MHz, CDCl3) δ 7.7,

Scheme 1. Lactone derivatization.

OH OH OH O 12.9, 28.1, 30.4, 46.8, 61.1, 72.2,

1) Bu2BOTf, CH2Cl2,
CO2tBu0 °C, 2 min, O SePh
Me SePh then DIEA H3 80.6, 173.6.
Me
1 1’
Me
B. Determination of relative
OH OH
1) Bu2BOTf, CH2Cl2, O
CO2tBu 0 °C, 2 min, O SePh
OH configuration for compounds 1-
Me SePh then DIEA
X-ray structure
19 19’ 3, 11, and 12.

A rigorous stereochemical assignment was performed for compound 1 and its syn

counterpart 19 (not presented in the present work), which were then transformed into

lactones. For lactone 19’, X-ray structure was elucidated. The 1H NMR spectra of lactones

derivatized from reduced products 2 and 3 were identical to those reported previously.2

Compound 19, yellow oil (83%). Rf 0.12 (hexanes-EtOAc, 6:4); IR (neat) υmax

3450, 1710 cm-1; MS (FAB) 360 (19, MH), 287 (49), 230 (28), 157 (19), 57 (100); 1H

NMR (400 MHz, CDCl3) δ 1.32 (s, 3H), 1.38 (s, 9H), 1.61-1.64 (m, 1H), 1.86-1.92 (m,

1H), 2.66 (t, J = 5.2 Hz, 1H), 3.57 (s, 1H), 3.78-3.88 (m, 2H), 4.07 (d, J = 10.2 Hz, 1H),

7.32 (t, J = 8 Hz, 2H), 7.40 (t, J = 8 Hz, 1H), 7.63 (d, J = 8 Hz, 2H); 13C NMR (100 MHz,

CDCl3) δ 17.4, 27.8, 33.4, 57.1, 61.7, 73.3, 81.9, 126.4, 128.9, 129.4, 138.2, 172.4; HRMS

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(FAB) calcd for C16H25O480Se: 361.0918, found: 361.0929 (-3.1 ppm); Anal. Calcd for

C16H24O4Se: C, 53.48; H, 6.73. Found: C, 53.31; H, 6.65.

Lactone 19’. To a solution of the syn phenylseleno ester 19 (120 mg, 0.33 mmol) in

CH2Cl2 (3.4 mL) at 0 °C was added Bu2BOTf (440 µL, 0.44 mmol). The reaction mixture

was stirred 1 min at the same temperature, and N,N-diisopropylethylamine (200 µL, 1.15

mmol) ) was added. After an additional 2 min, the solvent was removed, and the crude

residue was purified by flash chromatography to give the desired product 19’ as a white

solid (42 mg, 43%). Mp = 105-106 °C, Rf 0.28 (hexanes-EtOAc, 1:1); IR (CDCl3) υmax

3620, 1715 cm-1; MS (FAB) m/z 287 (100, MH+), 157 (62), 136 (63), 107 (31), 89 (36), 77

(47); 1H NMR (400 MHz, CDCl3) δ 1.52 (s,3H), 1.95 (qd, J = 14.6, 4.8 Hz, 1H), 2.33 (s,

1H), 2.47-2.56 (m, 1H), 4.22-4.30 (m, 1H), 4.35-4.40 (m, 1H), 4.63 (td, J = 10.8, 4.4 Hz,

1H), 7.34 (t, J = 7.6 Hz, 2H), 7.43 (t, J = 7.6 Hz, 1H), 7.61 (d, J = 8.4 Hz, 2H); 13C NMR

(100 MHz, CDCl3) δ 21.0, 27.9, 49.9, 65.5, 71.5, 126.3, 129.2, 130.0, 138.0, 172.3; HRMS

(FAB) calcd for C12H14O380Se: 287.0186, found: 287.0179 (2.6 ppm); Anal. Calcd for

C12H14O3Se: C, 50.54; H, 4.95. Found: C, 50.88; H, 4.90.

Lactone 1’, prepared from 1 (anti), was obtained as a yellow oil: Rf 0.19 (hexanes-

EtOAc, 1:1); MS (FAB) m/z 287 (44, MH+), 154 (100), 136 (88), 107 (32), 89 (35), 77

(40); 1H NMR (400 MHz, CDCl3) δ 1.59 (s,3H), 2.12-2.18 (m, 2H), 2.83 (d, J = 6.8, 1H),

3.79 (q, J = 6.4 Hz, 1H), 4.23-4.29 (m, 1H), 4.50-4.59 (m, 1H), 7.35 (t, J = 7.2 Hz, 2H),

7.44 (t, J = 6.8 Hz, 1H), 7.61 (d, J = 8.0 Hz, 2H); 13
C NMR (100 MHz, CDCl3) δ 23.3,

29.1, 56.8, 65.4, 71.1, 125.0, 129.2, 130.0, 138.3, 171.9.

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 The relative stereochemistry of the reduced products 11 and 12 was elucidated from

NMR studies of their corresponding benzylidene acetals 20 and 21. Acetal 20, which is

derivatized from anti product 11, is characterized by two large coupling constants (11Hz)

between Ha-Hc and Hc-Hd. The small coupling constants (2.5 Hz) between Ha-Hc and Hb-

Hc confirmed the syn relative stereochemistry between Me at C-2 and the hydroxyl group

at C-3 for acetal 21 and product 12.

Scheme 2. Benzylidene acetal derivatization.

Boc Boc
NH OH N OH N OH OH
Boc2O, THF, DIBAL,CH2Cl2
CO2tBu 25 °C CO2tBu -78 °C
Me Me Me
11:12, (3:1) (3:1)
Ph Hd Ph
Ha Ha
PhCH(OMe)2, p-TsOH O O O O
Me R O
O
Ph HRc
O
O
Ph
CH2Cl2, rt, 3 h H H
R 20, major b R 21, minor b
Hc Me
Me R = EtN(Boc)CH2CH2- Me R = EtN(Boc)CH2CH2-
JHaHb= 11.0 Hz; JHaHc= 11.0 Hz; JHaHb= 11.0 Hz; JHaHc= 2.5 Hz;
JHbHc= 4.5 Hz; JHcHd= 11.0 Hz; JHbHc= 2.5 Hz

Benzylidene acetal (20 and 21). To an inseparable (3:1) mixture of reduced products

11 and 12 (33.9 mg, 0.088 mmol) in THF (5 mL) was added di-tert-butyl dicarbonate

(Boc2O, 42 mg, 0.19 mmol). The reaction mixture was stirred at room temperature until

judged complete by TLC (12 h). After concentration, the two diastereoisomers were

separated by flash chromatography to afford N-Boc derivatives. Major: White solid, mp 48

° C; Rf 0.21 (CH2Cl2-EtOAc, 10:1); IR (CCl4) υmax 3430, 2975, 1720, 1695, 1480 cm-1;

MS (FAB) m/z 488 (12, MH+), 388 (16), 332(23), 258 (100); 1H NMR (400 MHz, CDCl3)

δ 1.12 (t, J = 7.0 Hz, 3H), 1.35 (s,3H), 1.41 (s, 9H), 1.46 (s, 9H), 2.17-2.24 (m, 2H), 3.22-

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3.37 (m, 4H), 3.90 (bs, 1H), 7.30 (t, J = 7.2 Hz, 2H), 7.44 (t, J = 6.8 Hz, 1H), 7.61 (d, J =

8.0 Hz, 2H); 13C NMR (100 MHz, CDCl3) δ 13.6, 18.0, 27.9, 28.5, 30.2, 42.3, 43.5, 54.6,

71.7, 79.3, 81.4, 128.7, 129.1, 138.0, 156.2, 172.9; HRMS (FAB) calcd for C23H38NO580Se:

488.1915, found: 488.1889; Anal. Calcd for C23H37NO5Se: C, 56.78; H, 7.67; N, 2.88.

Found: C, 56.62; H, 7.60; N, 2.89. Minor: light yellow oil; Rf 0.33 (CH2Cl2-EtOAc, 10:1);

IR (CCl4) υmax 3420, 2970, 1720, 1690, 1475 cm-1; MS (FAB) m/z 488 (20, MH+), 388

(38), 332(76), 176 (100); 1H NMR (400 MHz, CDCl3) δ 1.27 (t, J = 7.3 Hz, 3H), 1.37

(s,12H), 1.46 (s, 9H), 1.58-1.63 (m, 2H), 3.46-3.54 (m, 4H), 4.00 (bs, 1H), 7.30 (t, J = 7.2

Hz, 2H), 7.44 (t, J = 6.8 Hz, 1H), 7.61 (d, J = 8.0 Hz, 2H); 13C NMR (100 MHz, CDCl3) δ

13.5, 17.3, 27.7, 28.4, 30.5, 42.0, 43.6, 56.6, 70.2, 79.3 81.2, 128.7, 129.1, 138.1, 156.2,

171.9; HRMS (FAB) calcd for C23H38NO580Se: 488.1915, found: 488.1898; Anal. Calcd for

C23H37NO5Se: C, 56.78; H, 7.67; N, 2.88. Found: C, 56.62; H, 7.60; N, 2.89. To the

diastereoisomeric mixture (3:1) of N-Boc aminoesters (56.3mg, 0.17 mmol) in CH2Cl2 (2

mL) was added DIBAL (0.56 mL of 1M solution, 0.56 equiv) at –78 °C. The reaction

mixture was stirred 2 h at this temperature, quenched with MeOH (0.5 mL) and NH4Cl (2

mL) and then filtered through celite. The two phases were separated, and the aqueous layer

was extracted with CH2Cl2 (5 x 5 mL). The combined organic layers were washed with

brine (10 mL) and dried with Na2SO4, filtered, and concentrated under reduced pressure to

give 97% (43.2mg) of the diols, which were used for the next step without further

purification. To the CH2Cl2 solution (2 mL) of crude diols (43.2 mg, 0.165 mmol) were

added benzaldehyde dimethyl acetal (28 µL, 0.19 mmol) and a catalytic amount of p-

toluensulfonic acid. The resulting mixture was stirred 3 h at room temperature before being

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diluted with CH2Cl2 (20 mL), washed with saturated aq NaHCO3 (5 mL) and brine (5 mL),

and dried with Na2SO4. After filtration and evaporation of the solvent, the residue was

purified by flash chromatography (CH2Cl2:AcOEt, 20:1) to give 73% of desired

benzylidene acetals 20 and 21. The two diastereoisomers were separated by a second flash

chromatography (hexanes:EtOAc, 5:1). Major compound 20: oil; Rf 0.38

(Hexanes:EtOAc, 4:1); MS (FAB) m/z 350 (18, MH+), 292 (35), 250(59), 188 (71), 57

(100); 1H NMR (400 MHz, CDCl3) δ 0.81 (d, J = 6.7 Hz, 3H), 1.11 (t, J = 7.1 Hz, 3H), 1.47

(s, 9H), 1.67-1.72 (m, 1H), 1.88-1.93 (m, 1H), 2.09-2.15 (m, 1H) 3.26-3.34 (m, 5H), 3.36

(t, J = 11.1 Hz, 1H), 4.12 (dd, J = 11.1 and 4.5 Hz, 1H), 5.18 (s, 1H), 7.37-7.42 (m, 3H),

7.46-7.53 (m, 2H); 13C NMR (100 MHz, CDCl3) δ 12.4, 13.6, 28.5, 31.8, 33.8, 42.3, 43.3,

73.0, 79.0, 81.1, 100.9, 126.0, 128.2, 128.6, 138.6, 155.5; HRMS (FAB) calcd for

C20H32NO4: 350.2331, found: 350.2322; Anal. Calcd for C20H31NO4: C, 68.74; H, 8.94; N,

4.01. Found: C, 68.54; H, 8.90; N, 4.05. Minor compound 21: oil; Rf 0.25

(Hexanes:EtOAc, 4:1); MS (FAB) m/z 350 (17, MH+), 291 (27), 248(11), 188 (90), 57

(100); 1H NMR (400 MHz, CDCl3) δ 1.10 (d, J = 7.0 Hz, 3H), 1.21 (t, J = 7.0 Hz, 3H), 1.46

(s, 9H), 1.57-1.62 (m, 1H), 1.67-1.72 (m, 1H), 1.88-1.93 (m, 1H) 3.26-3.34 (m, 4H), 3.88-

3.93 (m, 1H), 4.03 (dd, J = 11.1 and 1.0 Hz, 1H), 4.10 (dd, J = 11.1 and 2.5 Hz, 1H), 5.49

(s, 1H), 7.37-7.42 (m, 3H), 7.46-7.53 (m, 2H); 13C NMR (100 MHz, CDCl3) δ 11.3, 12.4,

28.5, 32.0, 43.3, 73.8, 79.2, 101.7, 126.0, 128.2, 128.7, 153.9; HRMS (FAB) calcd for

C20H32NO4: 350.2331, found: 350.2326; Anal. Calcd for C20H31NO4: C, 68.74; H, 8.94; N,

4.01. Found: C, 68.54; H, 8.90; N, 4.05.

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