A stereodivergent approach to chiral nonracemic N-protected α,α-dialkylated amino acids

Article abstract of DOI:10.1021/ja037078a

Menthyl carboxaldehyde is used as a chiral auxiliary to make quaternary amino acids of either configuration via a stereodivergent approach that includes an S_N2′ displacement by a cuprate reagent and a Curtius rearrangement as key steps. Copyright

Full text of DOI:10.1021/ja037078a

S-1
Supporting Information
General: All reactions were performed under an inert atmosphere of argon in glassware that had
been oven or flame dried. Solvents were distilled from potassium/benzophenone ketyl (Et O,
THF, benzene, toluene) or from calcium hydride (CH Cl , triethylamine) prior to use. Reagents
2
2
2
were purchased from Aldrich and used without purification. Flash chromatography was
1
performed using Merck silica gel (230-400 Mesh ASTM) with solvents distilled prior to use. H
NMR spectra were recorded on a Bruker AC-300 (300 MHz) spectrometer. The following
abbreviations were used: s, singlet, d, doublet, q, quartet, qi, quintet, sx, sextet, sp, septet.
Chemical shifts are reported in ppm with the solvent resonance as the internal standard (CDCl
3
:
7
.26 ppm, DMSO-d : 2.49 ppm, acetone-d : 2.04 ppm). Infrared spectra were recorded on a
6
6
Perkin Elmer 1600 FTIR spectrometer with a thin layer of the product on a NaCl disk. High-
resolution spectrometry was performed on a ZAB-1F micromass spectrometer. Diastereomeric
and enantiomeric ratios were determined by gas chromatography (HP 5890 serie II, 25 m length,
2
5µ OD, capillary Stabiliwax-DB5 column) coupled with a mass spectrometer (HP 5971) or by
chiral HPLC (HP 1100, Chiralcel-OD and Chiralcel-OB columns).
Menthyl carboxyl chloride 1b.
Jones
(
ClCO)2
H
OH
Cl
DMF
O
O
O
1
a
1b
Aldehyde 1a (5.51 g, 32.7 mmol) was dissolved in acetone (130 mL) and cooled to 0 ºC,
whereupon an excess of Jones’ reagent was transferred dropwise via pipet until the reaction
solution remained orange coloured. This mixture was vigorously stirred at room temperature for
6
0 min. A few drops of 2-propanol were then added until the mixture remained green coloured
and the solvents were removed under reduced pressure. The green solid residue was dissolved in
water (50 mL) and this mixture was extracted with Et O (4 x 40 mL). The combined organic
2

S-2
layers were concentrated under reduced pressure until about 50 mL of solvent remained. Then it
was washed with 2N NaOH (3 x 50 mL), the combined basic layers were acidified at 0 ºC with
conc. HCl until the pH was adjusted to about 2. The white precipitate thus formed was extracted
with Et
2
O (3 x 40 mL), the combined ethereal layers were successively washed with one portion
of water and brine, dried over Na
2
SO
4
and concentrated under reduced pressure to afford 5.85 g
1
(
97 %) of white crystals. m.p. 57-58 ºC. H NMR (300 MHz, CDCl
3
): δ 12.08 (s, 1H), 2.30 (td,
J=11.6, 3.4 Hz, 1H), 1.92 (dq, J=12.5, 3.2 Hz, 1H), 1.81-1.65 (m, 3H), 1.50 (tt, J=11.4, 3.0 Hz,
H), 1.41-1.32 (m, 1H), 1.26-1.14 (m, 1H), 1.10-0.96 (m, 2H), 0.92 (d, J=6.8 Hz, 3H), 0.91 (d,
1
1
3
J=6.4 Hz, 3H), 0.81 (d, J=6.8 Hz, 3H). C NMR (75.5 MHz, CDCl ): δ 183.2 (s), 47.7 (d), 44.2
3
(
d), 38.8 (t), 34.5 (t), 32.0 (d), 29.3 (d), 23.8 (q), 22.3 (t), 21.3 (q), 16.0 (q). IR (neat): 3102,
+
2
951, 1706, 1445, 1294, 1198. LRMS (m/z): 184 (M , 25), 114 (90), 95 (100), 83 (45). HRMS
+
calcd. for C11
H
20
O
2
(M ): 184.1463, found: 184.1467.
The carboxylic acid (17.42 g, 94.5 mmol) and a catalytic amount of DMF (0.37 mL, 4.7 mmol)
was put in CH Cl (95 mL) and cooled to 0 ºC, followed by the slow addition of oxalyl chloride
9.9 mL, 113.4 mmol) over a 10 min period. When the reaction was completed (monitored by
2
2
(
NMR), the mixture was concentrated under reduced pressure to quantitatively afford an orange
oil, which was >95% pure as seen by NMR. The product could be distilled under vacuum (103-
1
1
11 ºC / 10 mmHg). In this way, 17.08 g (87 %) of colourless oil was isolated. H NMR (300
MHz, CDCl
3
): δ 2.73 (td, J=11.4, 3.4 Hz, 1H), 2.05 (dq, J=12.4, 2.9 Hz, 1H), 1.85-1.58 (m, 4H),
1
.45-1.35 (m, 1H), 1.30-1.18 (m, 1H), 1.10-0.89 (m, 2H), 0.94 (d, J=6.7 Hz, 6H), 0.82 (d, J=6.9
1
3
Hz, 3H). C NMR (75.5 MHz, CDCl
3
): δ 176.8 (s), 59.1 (d), 44.7 (d), 38.2 (t), 34.1 (t), 31.9 (d),
2
9.1 (d), 23.3 (t), 22.1 (q), 21.1 (q), 15.8 (q). IR (neat): 2959, 2873, 1793, 1454, 1006, 916, 849.
+
+
LRMS (m/z): 202 (M , 2), 166 ([M-HCl] , 30), 151 (55), 122 (80), 112 (80), 95 (90), 81 (100),
+
5
5 (85), 41 (70). HRMS calcd. for C11
H
19OCl (M ): 202.1124, found: 202.1129.

S-3
Alcohol 3a.
OH
TBSCl
OH
OTBDMS
H
O
AlMe3, Cp2ZrCl2
H
H
imidazole
OH
OH
CH Cl
2
2
1a
2
3a
Trimethyl aluminium (1.28 mL, 13.4 mmol) was added with caution to a solution of Cp
326 mg, 1.1 mmol) in CH Cl (8.9 mL) at room temperature. After stirring for 10 min. the
solution was cooled to 0 ºC and propargyl alcohol (250 mg, 4.5 mmol) in CH Cl (2.2 mL) is
2
ZrCl
2
(
2
2
2
2
added dropwise. The mixture was allowed to warm-up to room temperature and was stirred
overnight. Then, the solution was cooled down to –70 ºC and menthyl carboxaldehyde 1a (577
mg, 3.4 mmol) in THF (4.9 mL) was slowly added. The reaction mixture was stirred overnight
while allowing it to warm-up slowly to room temperature. The reaction was worked-up by
cooling to 0 ºC and adding slowly a saturated aqueous solution of potassium carbonate until the
evolution of gas stopped. The mixture was then acidified with 1N HCl at the same temperature
until all precipitate was dissolved. The organic phase was separated, washed with water, dried
over anhydrous MgSO
4
, filtered and reduced in vacuo. The resulting diol (636 mg) is unstable
1
and was used without further purification. H NMR analysis indicated a 10 : 1 ratio of the two
diastereomers.
The diol (636 mg, 2.6 mmol) was dissolved in CH
2
Cl (6.6 mL). At 0 ºC, imidazole (234 mg, 3.4
2
mmol) was added followed by TBDMSCl (479 mg, 3.2 mmol). The reaction was stirred for 4 h.
at room temperature. The mixture was then filtered through sintered glass to remove the salts and
brine was added. The organic phase was separated and dried over anhydrous MgSO , filtered,
4
and evaporated in vacuo. Flash chromatography of the resulting oil (hexanes : EtOAc, 9 : 1) gave
1
6
5
1
0
1
34 mg (68% for 2 steps) of alcohol 3a as a colourless oil. (3a): H NMR (300 MHz, CDCl
3
): δ
.63 (dq, J=8.2, 1.2 Hz, 1H), 4.71 (d, J=8.2 Hz, 1H), 4.03 (s, 2H), 2.19 (dsept, J=6.8, 1.5 Hz,
H), 1.72-1.60 (m, 3H), 1.64 (s, 3H), 1.43-1.19 (m, 4H), 0.94 (d, J=7.0 Hz, 3H), 0.92 (s, 9H),
1
3
.88 (d, J=6.5 Hz, 3H), 0.79 (d, J=6.9 Hz, 3H), 0.07 (s, 6H). C NMR (75.5 MHz, CDCl ): δ
3
35.8 (s), 126.2 (d), 67.9 (t), 67.3 (d), 44.8 (d), 43.1 (d), 35.1 (t), 34.1 (t), 32.8 (d), 26.3 (d), 25.9
+
(
q), 24.2 (t), 22.8 (q), 21.6 (q), 18.4 (s), 15.5 (q), 13.7 (q), -5.3 (q). LRMS (m/z): 366 ([M-H O] ,
2

S-4
+
2
3
), 145 (50), 131 (100), 75 (80). HRMS calcd. for C21
36.2838.
H
40OSi (M-H
2
O) : 336.2848, found :
Alcohol 3b.
Et BHLi
3
OTBDMS
OTBDMS
H
THF
H
O
OH
1
1
3b
Same procedure as per alcohol 5b via enone reduction (vide infra). Starting with 3.66 g (10.4
mmol) of enone 11, 3.04 g (82%) of colourless oil was isolated after purification by flash
chromatography (Et
2
O/hexanes, 20:80). GLC analysis of the crude residue indicated only one
1
diastereomer (>99% d.e.). (3b): H NMR (300 MHz, CDCl
3
): δ 5.63 (dq, J=9.4, 1.4 Hz, 1H),
4
.64 (dd, J=9.4, 4.1 Hz, 1H), 4.03 (s, 2H), 1.95 (dq, J=12.5, 3.0 Hz, 1H), 1.82 (dsept, J=6.9, 2.6
Hz, 1H), 1.73-1.59 (m, 4H), 1.68 (s, 3H), 1.36-1.27 (m, 1H), 1.25 (s, 1H), 1.03-0.93 (m, 3H),
.92 (s, 9H), 0.89 (d, J=6.6 Hz, 3H), 0.82 (d, J=6.9 Hz, 3H), 0.79 (d, J=7.0 Hz, 3H), 0.06 (s, 6H).
13C NMR (75.5 MHz, CDCl
): δ 139.1 (s), 122.0 (d), 67.8 (t), 67.4 (d), 44.5 (d), 43.9 (d), 35.2
t), 34.1 (t), 32.5 (d), 26.5 (d), 25.8 (q), 24.1 (t), 22.8 (q), 21.5 (q), 18.3 (s), 15.3 (q), 13.7 (q), -
0
3
(
5
.3 (q). IR (neat): 3617, 3368, 2929, 2854, 1676, 1460, 1253, 1109, 1025, 848. LRMS (m/z): 336
+
+
(
[M-H
2
O] , 5), 215 (75), 83 (100). HRMS calcd. for C21
H
40OSi (M-H
2
O) : 336.2848, found :
2
0
3
36.2845. [α]
D
= -15.0º (c 2.21, CHCl ).
3
Pivalate ester 4b.
PivCl
OTBDMS
OTBDMS
H
H
O
DMAP
OH
O
3
b
4b

S-5
Same procedure as per pivalate 7b (vide infra). Starting with 1.04 g (2.9 mmol) of alcohol 3b,
1
.23 g (95%) of colourless oil was isolated after purification by flash chromatography
1
(
Et
2
O/hexanes, 8:92). H NMR (300 MHz, CDCl
3
): δ 5.72 (dd, J=9.7, 4.0 Hz, 1H), 5.56 (dq,
J=9.6, 1.3 Hz, 1H), 4.01 (s, 2H), 1.91-1.79 (m, 2H), 1.74-1.55 (m, 3H), 1.64 (d, J=0.6 Hz, 3H),
.41-1.18 (m, 1H), 1.16 (s, 9H), 1.05-0.75 (m, 4H), 0.90 (s, 9H), 0.88 (d, J=6.5 Hz, 3H), 0.84 (d,
1
1
3
J=7.0 Hz, 3H), 0.82 (d, J=6.8 Hz, 3H), 0.04 (s, 6H). C NMR (75.5 MHz, CDCl
40.9 (s), 117.8 (d), 70.5 (d), 67.5 (t), 43.7 (d), 42.6 (d), 38.9 (s), 35.1 (t), 34.9 (t), 32.4 (d), 27.2
q), 26.7 (d), 25.8 (q), 23.9 (t), 22.8 (q), 21.4 (q), 18.4 (s), 15.3 (q), 14.0 (q), -5.3 (q). IR (neat):
3
): δ 177.6 (s),
1
(
2
7
954, 2858, 1723, 1459, 1283, 1155, 838. LRMS (m/z): 381 ([M-C
4
H
]+, 5), 205 (100), 159 (90),
9
+
4 (100). HRMS calcd. for C22
H
41
O
3
Si (M-C
4
H
9
) : 381.2825, found : 381.2816.
Pivalate ester 4a.
PivCl
OTBDMS
OTBDMS
H
H
DMAP
OH
O
O
3a
4a
Same procedure as per pivalate 7b (vide infra). Starting with 147 mg (0.4 mmol) of alcohol 3a,
1
59 mg (64%) of colourless oil was isolated after purification by flash chromatography
1
(
hexanes/EtOAc, 30:1). H NMR (300 MHz, CDCl
3
): δ 5.66 (dd, J=8.8, 2.3 Hz, 1H), 5.47 (dq,
J=8.8, 1.1 Hz, 1H), 4.02 (s, 2H), 2.02 (dt, J=6.8 and 2.8 Hz, 2H), 1.85-1.77 (m, 1H), 1.71-1.58
m, 3H), 1.49-1.37 (m, 1H), 1.28-1.10 (m, 3H), 1.17 (s, 9H), 1.01-0.91 (m, 4H), 0.90 (s, 9H),
(
0
3
.87 (d, J=6.9 Hz, 3H), 0.77 (d, J=7.3 Hz, 3H), 0.04 (s, 6H). IR (neat): 1727, 1461. LRMS (m/z):
81 ([M-C
]+, 5), 205 (100), 159 (70), 74 (100).
4
H
9

S-6
Alcohols 5a and 5b from the carbomagnesiation/addition.
OH
TBSCl
imidazole
H
PhMgCl, CuI
THF
H
H
O
OH
OH
OH
OTBDMS
1a
5a-b
2
.9 mL (50.0 mmol) of propargyl alcohol was dissolved in 100 mL THF containing 1.90 g (10.0
mmol) of CuI. This suspension was degassed and purged with argon atmosphere prior to the
dropwise addition of commercially available phenylmagnesium chloride (2.0M THF solution; 75
mL, 150.0 mmol). This suspension was heated under reflux until complete consumption of the
propargyl alcohol as seen by GLC analysis. The mixture was then cooled to 0°C and 26.92 g
(
160.0 mmol) of aldehyde 1a was slowly added as a THF solution (40 mL). The reaction mixture
was heated under reflux for 2 h and was quenched at 0°C with 250 mL of saturated aqueous
solution of NH Cl / NH OH (9:1). The layers were separated and the aqueous layer was
extracted with Et O (4 x 100 mL). The combined organic layers were washed with brine, dried
MgSO ) and concentrated under reduced pressure. As seen by H NMR, the crude residue
4
4
2
1
(
4
contained a 1.7:1 mixture of diastereomeric diols which could be easily separated by flash
chromatography eluting with hexanes/EtOAc, (80:20). In this way, 10.49 g (69%, combined
1
yield) of the mixture of diols was obtained as a colourless oil. major diol: H NMR (300 MHz,
CDCl
Hz, 1H), 4.51 (d, J=12.4 Hz, 1H), 2.19 (dsept, J=6.9, 2.9 Hz, 1H), 2.05 (s, 2H), 1.78-1.68 (m,
H), 1.48-1.29 (m, 3H), 1.09-0.82 (m, 3H), 0.97 (d, J=6.8 Hz, 3H), 0.89 (d, J=6.5 Hz, 3H), 0.82
3
): δ 7.48-7.45 (m, 2H), 7.38-7.29 (m, 3H), 4.92 (dd, J=7.2, 2.2 Hz, 1H), 4.64 (d, J=12.3
3
1
3
(
d, J=6.9 Hz, 3H). C NMR (75.5 MHz, CDCl ): δ 140.8 (s), 135.7 (s), 133.7 (d), 128.6 (d),
3
1
27.5 (d), 126.4 (d), 67.6 (d), 60.6 (t), 45.3 (d), 43.1 (d), 35.0 (t), 34.0 (t), 32.7 (d), 26.4 (d), 24.2
(
(
t), 22.8 (q), 21.6 (q), 15.6 (q). IR (neat): 3365, 2953, 2868, 1693, 1455, 1020, 759, 697. LRMS
+
m/z): 284 ([M-H
2
O] , 5), 163 (100), 145 (70), 117 (80), 83 (70). HRMS calcd. for C20
H28O (M-
+
1
H
2
O) : 284.2140, found: 284.2134. minor diol: H NMR (300 MHz, CDCl
3
): δ 7.44-7.41 (m,
2
1
2
H), 7.37-7.28 (m, 3H), 6.00 (d, J=8.5 Hz, 1H), 4.80 (dd, J=8.5, 4.2 Hz, 1H), 4.66 (d, J=12.2 Hz,
H), 4.41 (d, J=12.2 Hz, 1H), 3.57 (s, 2H), 2.01-1.97 (m, 1H), 1.83-1.64 (m, 4H), 1.39-1.27 (m,
H), 1.07-0.79 (m, 3H), 0.92 (d, J=6.5 Hz, 3H), 0.86 (d, J=6.8 Hz, 3H), 0.82 (d, J=7.0 Hz, 3H).

S-7
13C NMR (75.5 MHz, CDCl
): δ 143.2 (s), 141.2 (s), 129.7 (d), 128.4 (d), 127.5 (d), 126.4 (d),
3
6
7.4 (d), 60.2 (t), 44.4 (d), 44.0 (d), 35.0 (t), 33.9 (t), 32.4 (d), 26.6 (d), 24.1 (t), 22.7 (q), 21.5
(
q), 15.4 (q). IR (neat): 3371, 2948, 2865, 1651, 1457, 1260, 1018. LRMS (m/z): 284 ([M-H
2
O]+,
+
3
), 163 (100), 145 (60), 117 (85), 83 (80). HRMS calcd. for C H O (M-H O) : 284.2140,
2
0
28
2
found: 284.2148.
The mixture of diols (9.57g, 31.6 mmol) was dissolved in 315 mL CH
2
Cl
2
with 2.58 g (38.0
mmol) of imidazole. Then, 5.01 g (33.2 mmol) of t-butyldimethylsilyl chloride was added
portionwise. This mixture was stirred at room temperature for 6 h, and 150 mL of water was
added. The layers were separated, the aqueous layer was extracted with CH
and the combined organic layers were washed with brine, dried (MgSO ) and concentrated under
reduced pressure. The residue was purified by flash chromatography eluting with hexanes/Et
2
Cl
2
(3 x 100 mL)
4
2
1
O
(
85:15) to afford 13.19 g (100%, combined yield) of both alcohols as colourless oil. (5a): H
NMR (300 MHz, CDCl ): δ 7.42-7.39 (m, 2H), 7.35-7.27 (m, 3H), 5.98 (d, J=7.2 Hz, 1H), 4.90
3
(
d, J=7.2 Hz, 1H), 4.64 (d, J=12.1 Hz, 1H), 4.53 (d, J=12.1 Hz, 1H), 3.48 (s, 1H), 2.22 (dsept,
J=7.0, 1.9 Hz, 1H), 1.80-1.70 (m, 3H), 1.44-1.27 (m, 3H), 1.11-0.86 (m, 3H), 0.98 (d, J=6.8 Hz,
1
3
3
H), 0.90 (d, 6.4 Hz, 3H), 0.87 (s, 9H), 0.83 (d, J=7.0 Hz, 3H), 0.06 (s, 6H). C NMR (75.5
MHz, CDCl ): δ 141.7 (s), 140.0 (s), 134.2 (d), 128.1 (d), 127.1 (d), 126.7 (d), 67.4 (d), 61.2 (t),
5.2 (d), 43.1 (d), 35.1 (t), 34.1 (t), 32.8 (d), 26.3 (d), 25.8 (q), 24.3 (t), 22.8 (q), 21.6 (q), 18.2
3
4
(
(
s), 15.7 (q), -5.3 (q). IR (neat): 3434, 3024, 2956, 2853, 1599, 1463, 1255, 1075, 836. LRMS
+
42OSi (M-H
O)+:
m/z): 398 ([M-H
2
O] , 15), 277 (85), 145 (95), 74 (100). HRMS calcd. for C26
H
2
1
3
98.3005, found: 398.3013. (5b): H NMR (300 MHz, CDCl
3
): δ 7.39-7.26 (m, 5H), 6.04 (d,
J=8.2 Hz, 1H), 4.82 (dd, J=8.2, 4.3 Hz, 1H), 4.69 (d, J=12.1 Hz, 1H), 4.55 (d, J=12.1 Hz, 1H),
2
1
3
.81 (s, 1H), 2.04 (dq, J=12.6, 3.0 Hz, 1H), 1.86 (dsept, J=6.9, 1.7 Hz, 1H), 1.82-1.64 (m, 4H),
.44-1.32 (m, 1H), 1.12-0.80 (m, 3H), 0.91 (d, J=7.7 Hz, 3H), 0.90 (s, 9H), 0.87 (d, J=6.8 Hz,
1
3
H), 0.83 (d, J=6.9 Hz, 3H), 0.11 (s, 3H), 0.09 (s, 3H). C NMR (75.5 MHz, CDCl ): δ 143.2
3
(
(
(
s), 142.1 (s), 130.9 (d), 128.2 (d), 127.3 (d), 126.6 (d), 67.1 (d), 62.1 (t), 44.1 (d), 43.7 (d), 35.2
t), 33.9 (t), 32.5 (d), 26.6 (d), 25.8 (q), 24.3 (t), 22.8 (q), 21.6 (q), 18.2 (s), 15.4 (q), -5.4 (q), -5.5
q). IR (neat): 3411, 3023, 2948, 2852, 1599, 1462, 1253, 1093, 837. LRMS (m/z): 398 ([M-
+
H H42OSi (M-
]+, 5), 277 (90), 145 (85), 74 (100). HRMS calcd. for C26
H
H
2
O] , 10), 359 ([M-C
4
9
+
2
O) : 398.3005, found: 398.3013.

S-8
Alcohol 5b via reduction of the enone:
Swern
Et BHLi
3
H
H
THF
H
OH
O
OH
OTBDMS
OTBDMS
OTBDMS
5
a-b
5b
0
.48 mL (6.8 mmol) of dimethylsulfoxide was added to a solution of 0.30 mL (3.4 mmol) of
oxalyl chloride in 13.6 mL CH Cl . This solution was stirred at -78°C for 5 min, whereupon 1.29
g (3.1 mmol) of a mixture containing both alcohols 5a and 5b was added as a 6.2 mL CH
solution. This solution was stirred for 15 min at -78°C, and then 2.2 mL (15.4 mmol) of Et
2
2
2
Cl
2
3
N
was slowly added. The reaction solution was then allowed to warm slowly to room temperature
over 2 h, after which time 15.0 mL of water was poured and the mixture was extracted with
CH
2
Cl
2
(3 x 10 mL) The combined organic layers were washed with brine, dried (MgSO
4
),
concentrated under reduced pressure and was used as such for the next step. A pure sample was
obtained as colourless oil after purification by flash chromatography (Et
2
O/hexanes, 2:98).
1
Enone : H NMR (300 MHz, CDCl
3
): δ 7.49-7.43 (m, 2H), 7.37-7.32 (m, 3H), 6.43 (s, 1H), 5.12
(
(
(
d, J=1.0 Hz, 2H), 2.53 (dt, J=11.5, 3.2 Hz, 1H), 1.83-1.58 (m, 5H), 1.43-1.34 (m,1H), 1.11-0.82
1
3
m, 3H), 0.89 (d, J=7.1 Hz, 6H), 0.78 (d, J=6.8 Hz, 3H), 0.72 (s, 9H), -0.05 (s, 6H). C NMR
75.5 MHz, CDCl ): δ 205.2 (s), 158.6 (s), 139.4 (s), 128.6 (d), 128.0 (d), 127.9 (d), 124.3 (d),
0.4 (t), 55.5 (d), 44.4 (d), 38.8 (t), 34.6 (t), 32.4 (d), 29.0 (d), 25.6 (q), 24.0 (t), 22.4 (q), 21.4
3
6
(
q), 18.0 (s), 16.2 (q), -5.5 (q). IR (neat): 2952, 2857, 1677, 1596, 1470, 1368, 1255, 1098, 843.
+
H
]+, 70), 105 (35), 74 (100). HRMS calcd. for
LRMS (m/z): 414 (M , 20), 357 ([M-C
4
9
+
C
26
H
42
O
2
Si (M) : 414.2954, found: 414.2957.
The crude enone was dissolved in 62 mL THF and cooled at -78°C, whereupon 3.3 mL (1.0M
THF solution; 3.3 mmol) of lithium triethylborohydride was slowly added. The reaction was
completed in 5 min and was quenched with 30 mL of a saturated solution of ammonium
chloride. The mixture was allowed to warm to room temperature and was concentrated under
reduced pressure. The ammonium salts were dissolved with additional water (15 mL), the
resulting homogeneous solution was cooled to 0°C and 4.6 mL of H
2
2
O (30% in water) was

S-9
added. This mixture was vigorously stirred for 1 h at 0°C after which time it was poured into a
cold saturated solution of sodium bicarbonate and was extracted with Et
2
O (3 x 25 mL), the
combined organic extracts were washed with brine, dried (MgSO ) and concentrated in vacuo.
4
GLC analysis of the crude residue indicated only one diastereomer (>99% d.e.), which was
purified by flash chromatography eluting with hexanes/EtOAc, (92:8) to afford 994 mg (77%, 2
steps) of alcohol 5b.
Alcohols 6a and 6b from the carbomagnesiation/addition.
OH
TBSCl
OMe
OMe
OTBDMS
H
m-MeO-PhMgBr
CuI, THF
H
imidazole
H
O
OH
OH
OH
1
a
6a-b
Same procedure as per alcohols 5a and 5b. 0.12 mL (2.0 mmol) of propargyl alcohol afforded
3
56 mg (54%, combined yield) of the diastereomeric diols after purification by flash
chromatography (hexanes/EtOAc, 80:20). As seen by 1H NMR of the crude, the
1
diastereoselectivity was 1.4:1. major diol: H NMR (300 MHz, CDCl
3
): δ 7.27 (dd, J=8.3 Hz,
1
H), 7.04 (d, J=7.7 Hz, 1H), 7.00 (d, J=2.2 Hz, 1H), 6.84 (dd, J=8.3, 2.8 Hz, 1H), 6.02 (d, J=7.2
Hz, 1H), 4.91 (dd, J=7.2, 2.2 Hz, 1H), 4.62 (d, J=12.7 Hz, 1H), 4.48 (d, J=12.1 Hz, 1H), 3.83 (s,
3
0
H), 2.17 (dsept, J=7.2, 2.8 Hz, 1H), 2.15 (s, 1H), 1.76-1.68 (m, 4H), 1.47-1.25 (m, 3H), 1.08-
1
3
.92 (m, 2H), 0.96 (d, J=6.6 Hz, 3H), 0.89 (d, J=6.6 Hz, 3H), 0.81 (d, J=6.6 Hz, 3H). C NMR
): δ 159.7 (s), 142.3 (s), 140.6 (s), 133.9 (d), 129.5 (d), 118.9 (d), 112.8 (d),
12.3 (d), 67.6 (d), 60.6 (t), 55.3 (q), 45.3 (d), 43.1 (d), 35.0 (t), 34.0 (t), 32.7 (d), 26.4 (d), 24.2
(75.5 MHz, CDCl
3
1
(
t), 22.8 (q), 21.6 (q), 15.6 (q). IR (neat): 3382, 2953, 2872, 1599, 1577, 1452, 1285, 1024.
+
LRMS (m/z): 314 ([M-H
2
O] , 10), 193 (100), 175 (80), 147 (95), 83 (80). HRMS calcd. for
+
1
C H O (M-H O) : 314.2246, found: 314.2240. minor diol: H NMR (300 MHz, CDCl ): δ
2
1
30
2
2
3
7
6
1
1
.30-7.24 (m, 1H), 7.01 (d, J=8.3 Hz, 1H), 6.97 (t, J=2.2 Hz, 1H), 6.85 (dd, J=8.3, 2.8 Hz, 1H),
.01 (d, J=8.3 Hz, 1H), 4.81 (dd, J=8.3, 4.4 Hz, 1H), 4.68 (d, J=12.1 Hz, 1H), 4.46 (d, J=12.1 Hz,
H), 3.82 (s, 3H), 2.77 (s, 2H), 1.95 (dq, J=12.6, 2.8 Hz, 1H), 1.84 (sept, J=6.6 Hz, 1H), 1.75-
.61 (m, 4H), 1.36-1.25 (m, 1H), 1.07-0.94 (m, 3H), 0.91 (d, J=6.6 Hz, 3H), 0.85 (d, J=7.1 Hz,

S-10
1
3
3
1
3
2
8
H), 0.82 (d, J=7.2 Hz, 3H). C NMR (75.5 MHz, CDCl ): δ 159.6 (s), 143.8 (s), 142.8 (s),
3
29.9 (d), 129.5 (d), 118.9 (d), 112.6 (d), 112.5 (d), 67.6 (d), 60.8 (t), 55.3 (q), 44.5 (d), 44.1 (d),
5.1 (t), 33.9 (t), 32.5 (t), 26.7 (d), 24.2 (t), 22.7 (q), 21.6 (q), 15.4 (q). IR (neat): 3397, 2954,
+
869, 1644, 1604, 1455, 1286. LRMS (m/z): 314 ([M-H
2
O] , 10), 193 (100), 175 (65), 147 (70),
+
3 (75). HRMS calcd. for C21
H
30
O
2
(M-H
2
O) : 314.2246, found: 314.2243.
A mixture of 310 mg (0.9 mmol) of diols were treated as above. The reaction afforded 372 mg
(
89%, combined yield) of a mixture of silyl ethers 6a and 6b as a colourless oil after purification
1
by flash chromatography (Et
2
O/hexanes, 10:90). (6a): H NMR (300 MHz, CDCl
3
): δ 7.24 (t,
J=7.7 Hz, 1H), 6.99 (d, J=7.7 Hz, 1H), 6.96 (d, J=2.2 Hz, 1H), 6.82 (dd, J=8.3, 2.2 Hz, 1H), 5.99
(
(
d, J=7.2 Hz, 1H), 4.89 (d, J=7.2 Hz, 1H), 4.61 (d, J=11.8 Hz, 1H), 4.50 (d, J=11.8 Hz, 1H), 3.82
s, 3H), 2.35 (s, 1H), 2.20 (sp, J=6.6, 0.6 Hz, 1H), 1.79-1.67 (m, 4H), 1.47-1.26 (m, 3H), 1.09-
0
3
1
3
.86 (m, 2H), 0.97 (d, J=6.6 Hz, 3H), 0.89 (d, J=6.1 Hz, 3H), 0.88 (s, 9H), 0.83 (d, J=6.6 Hz,
1
3
H), 0.07 (s, 6H). C NMR (75.5 MHz, CDCl ): δ 159.4 (s), 143.3 (s), 139.8 (s), 134.5 (d),
3
29.1 (d), 119.2 (d), 112.5 (d), 112.4 (d), 67.4 (d), 61.3 (t), 55.2 (q), 45.1 (d), 43.1 (d), 35.1 (t),
4.1 (t), 32.8 (d), 26.3 (d), 25.8 (q), 24.3 (t), 22.8 (q), 21.6 (q), 18.2 (s), 15.7 (q), -5.3 (q). IR
+
(
(
(
neat): 3449, 2952, 2852, 1598, 1463, 1252, 1058, 834. LRMS (m/z): 418 ([M-H
2
O] , 2), 389
+
[M-C
4
H
9
] , 10), 307 (100), 175 (95), 159 (80), 139 (50), 74 (90). HRMS calcd. for C23
H
37
O
3
Si
): δ 7.28-7.23 (m, 1H),
.95-6.90 (m, 2H), 6.83 (dd, J=8.3, 2.8 Hz, 1H), 6.05 (d, J=8.3 Hz, 1H), 4.82 (dd, J=8.3, 4.4 Hz,
+
1
M-C
4
H
9
) : 389.2512, found: 389.2509. (6b): H NMR (300 MHz, CDCl
3
6
1
2
3
H), 4.67 (d, J=11,8 Hz, 1H), 4.52 (d, J=11.8 Hz, 1H), 3.82 (s, 3H), 2.83 (s, 1H), 2.03 (dq, J=9.9,
.5 Hz, 1H), 1.86 (sp, J=6.6, 0.6 Hz, 1H), 1.80-1.65 (m, 3H), 1.43-1.33 (m, 2H), 1.11-0.79 (m,
1
3
H), 0.90 (s, 9H), 0.87 (d, J=6.6 Hz, 6H), 0.83 (d, J=7.2 Hz, 3H), 0.12 (s, 3H), 0.10 (s, 3H). C
): δ 159.4 (s), 143.8 (s), 143.1 (s), 131.2 (d), 129.2 (d), 119.1 (d), 112.6
d), 112.4 (d), 67.1 (d), 62.2 (t), 55.2 (q), 44.1 (d), 43.7 (d), 35.2 (t), 33.9 (t), 32.5 (d), 26.7 (d),
NMR (75.5 MHz, CDCl
3
(
2
2
5.8 (q), 24.3 (t), 22.7 (q), 21.6 (q), 18.2 (s), 15.4 (q), -5.4 (q), -5.5 (q). IR (neat): 3447, 2952,
855, 1597, 1463, 1253, 1050, 836. LRMS (m/z): 389 ([M-C
4
H
]+, 5), 307 (100), 175 (90), 74
9
+
(
100). HRMS calcd. for C23
H
37
O
3
Si (M-C
4
H
9
) : 389.2512, found: 389.2509.

S-11
Alcohol 6b via reduction of the enone:
OMe
OMe
OMe
Swern
Et BHLi
3
H
H
THF
H
OH
a-b
OH
OH
OTBDMS
OTBDMS
OTBDMS
6
6b
Same procedure as above for alcohol 5b. Starting with 1.14 g (2.6 mmol) of a mixture of
alcohols 6a and 6b afforded 846 mg (74%, 2 steps) of 6b after purification by flash
chromatography (EtOAc/hexanes, 8:92). GLC analysis of the crude residue indicated only one
1
diastereomer (>99% d.e.) corresponding to alcohol 6b. Enone: H NMR (300 MHz, CDCl
3
): δ
7
2
.27 (t, J=8.0 Hz, 1H), 7.07-7.03 (m, 2H), 6.89 (dd, J=8.0, 2.5 Hz, 1H), 6.43 (s, 1H), 5.09 (s,
H), 3.83 (s, 3H), 2.52 (td, J=11.7, 3.1 Hz, 1H), 1.81-1.58 (m, 5H), 1.46-1.32 (m, 1H), 1.10-0.94
(
m, 3H), 0.90 (d, J=6.60 Hz, 3H), 0.89 (d, J=7.2 Hz, 3H), 0.78 (d, J=7.2 Hz, 3H), 0.73 (s, 9H), -
1
3
0
1
3
2
.04 (s, 6H). C NMR (75.5 MHz, CDCl ): δ 205.2 (s), 159.2 (s), 158.0 (s), 141.1 (s), 128.8 (d),
3
24.5 (d), 120.4 (d), 114.0 (d), 113.7 (d), 60.3 (t), 55.5 (d), 55.3 (q), 44.4 (d), 38.8 (t), 34.6 (t),
2.4 (d), 29.0 (d), 25.6 (q), 23.9 (t), 22.3 (q), 21.4 (q), 18.1 (s), 16.1 (q), -5.4 (q). IR (neat): 2952,
+
H
]+, 100), 74 (55).
854, 1674, 1597, 1465, 1252. LRMS (m/z): 444 (M , 20), 387 ([M-C
4
9
+
HRMS calcd. for C27
H
44
O
3
Si (M) : 444.3060, found: 444.3062.
Pivalate ester 7a.
PivCl
H
H
DMAP
OH
O
OTBDMS
OTBDMS
O
5
a
7a
Same procedure as per ester 7b (vide infra). Starting with 3.04 g (7.3 mmol) of alcohol 5a, we
obtained 3.65 g (100%) of a colourless oil. The crude residue was used as such in the next
reaction.

S-12
Pivalate ester 7b.
PivCl
H
H
DMAP
OH
O
OTBDMS
OTBDMS
O
5
b
7b
9
60 mg (2.3 mmol) of alcohol 5b was dissolved in 23 mL CH
2
Cl
2
with 42.2 mg (0.3 mmol) of 4-
dimethylaminopyridine and 1.3 mL (9.2 mmol) of Et
3
N. Then 0.60 mL (4.6 mmol) of
trimethylacetyl chloride was added dropwise over 10 min. The reaction solution was stirred at
room temperature until completion as seen by TLC. Then a saturated solution of ammonium
chloride (15 mL) was poured, the layers were separated and the aqueous phase was extracted
with CH
2
Cl
2
(3 x 10 mL). The combined organic layers were washed with brine, dried (MgSO
4
)
and the solvents were removed under reduced pressure to afford an oil which could be used as
such for the next step. The crude residue was purified by flash chromatography (Et
2
O/hexanes,
1
2
:98) and 1.00 g (87%) of colourless oil was isolated. H NMR (300 MHz, CDCl
3
): δ 7.43-7.40
(
m, 2H), 7.36-7.27 (m, 3H), 5.91 (dd, J=9.7, 3.8 Hz, 1H), 5.81 (d, J=9.6 Hz, 1H), 4.69 (d, J=12.3
Hz, 1H), 4.55 (d, J=12.3 Hz, 1H), 2.03 (dsept, J=6.8, 2.3 Hz, 1H), 1.91-1.63 (m, 4H), 1.34-1.24
(
m, 1H), 1.22 (s, 9H), 1.09-0.83 (m, 4H), 0.92 (d, J=7.1 Hz, 3H), 0.89 (d, J=7.0 Hz, 6H), 0.80 (s,
1
3
9
1
3
H), 0.02 (s, 3H), -0.02 (s, 3H). C NMR (75.5 MHz, CDCl ): δ 177.5 (s), 144.5 (s), 141.3 (s),
3
27.9 (d), 127.2 (d), 124.5 (d), 70.5 (d), 60.2 (t), 44.1 (d), 42.8 (d), 38.9 (s), 35.4 (t), 35.1 (t),
2.5 (d), 27.2 (q), 26.7 (d), 25.7 (q), 24.0 (t), 22.8 (q), 21.7 (q), 18.1 (s), 15.3 (q), -5.5 (q). IR
(
neat): 3025, 2929, 1723, 1477, 1388, 1282, 1254, 1077, 774. LRMS (m/z): 443 ([M-C
4
H
9
]+, 5),
) : 443.2981,
+
3
98 (20), 267 (75), 159 (100), 74 (85). HRMS calcd. for C27
H
43
O
3
Si (M-C
4
H
9
found: 443.2976.48

S-13
Pivalate ester 8a.
PivCl
OMe
OTBDMS
OMe
OTBDMS
H
H
DMAP
OH
O
O
6
a
8a
Same procedure as per ester 7b. Starting with 1.88 g (4.2 mmol) of alcohol 6a, we obtained 1.87
1
g (84%) of a white solid after purification by flash chromatography (Et
NMR (300 MHz, CDCl
.97 (d, J=2.8 Hz, 1H), 6.81 (dd, J=8.3 and 2.8 Hz, 1H), 5.84 (dd, J = 8.8 and 2.8 Hz, 1H), 5.75
d, J = 8.8 Hz, 1H), 4.68 (d, J=11.8 Hz, 1H), 4.51 (d, J=11.8 Hz, 1H), 3,81 (s, 3H), 2.01 (dsp,
J=6.6 Hz, 1H), 1.91-1.85 (m, 1H), 1.75-1.55 (m, 4H), 1.41-1.17 (m, 1H), 1.20 (s, 9H), 1.09-0.85
m, 3H), 0.90 (d, J=6.6 Hz, 3H), 0.89 (d, J=6.6 Hz, 3H), 0.83 (d, J=7.7 Hz, 1H), 0.81 (s, 9H),
.02 (s, 3H), -0.01 (s, 3H).
2
O/hexanes, 2:98). H
3
): δ 7.25-7.20(m, 1H), 7.00 (d, J=8.8 Hz, 1H), 6.99 (d, J=9.9 Hz, 1H),
6
(
(
0
Pivalate ester 8b.
PivCl
OMe
OTBDMS
OMe
OTBDMS
H
H
DMAP
OH
O
O
6
b
8b
Same procedure as per ester 7b. Starting with 1.88 g (4.2 mmol) of alcohol 6b, 1.87 g (84%) of
colourless oil was isolated after purification by flash chromatography (Et
2
O/hexanes, 2:98). The
): δ 7.23
1
crude residue was usually used as such for the next reaction. H NMR (300 MHz, CDCl
3
(
d, J=8.3 Hz, 1H), 6.99 (d, J=9.9 Hz, 1H), 6.97 (d, J=2.2 Hz, 1H), 6.82 (dd, J=5.5, 2.8 Hz, 1H),
5
1
1
0
.87 (dd, J=9.9, 3.9 Hz, 1H), 5.81 (d, J=9.9 Hz, 1H), 4.64 (d, J=12.1 Hz, 1H), 4.50 (d, J=12.1 Hz,
H), 3,82 (s, 3H), 2.00 (dsp, J=6.6 Hz, 1H), 1.86-1.63 (m, 6H), 1.35-1.24 (m, 1H), 1.19 (s, 9H),
.08-0.80 (m, 2H), 0.90 (d, J=6.6 Hz, 3H), 0.87 (d, J=6.6 Hz, 6H), 0.79 (s, 9H), 0.02 (s, 3H), -
.02 (s, 3H).

S-14
Vinyl silane 10.
SiMe3
MeMgCl
CuI, THF
Me
HO
SiMe3
TBSCl
Me
TBDMSO
SiMe3
imidazole
HO
9
10
1
8.20 g (141.9 mmol) of 3-trimethylsilyl-2-propyn-1-ol 9 was dissolved in 360 mL Et O
2
containing 2.70 g (14.2 mmol) of CuI. This suspension was degassed and purged with argon
atmosphere prior to the dropwise addition of commercially available methylmagnesium chloride
(
3.0M THF solution; 105 mL, 315.0 mmol). This suspension was heated under reflux until
complete consumption of the starting material as seen by GLC analysis. The mixture was then
cooled to 0°C and was slowly quenched with 300 mL of saturated aqueous solution of NH Cl /
NH OH (9:1). The layers were separated and the aqueous layer was extracted with Et O (4 x 150
mL). The combined organic layers were washed with brine, dried (MgSO ) and concentrated
4
4
2
4
under reduced pressure to afford 19.11 g (93%) of yellowish oil, which was used in the next
reaction without further purification.
The crude vinyl silane (10.19 g, 67.7mmol) was dissolved in 100 mL CH
2
Cl and cooled to 0 ºC.
2
Imidazole (5.53 g, 81.2 mmol) and t-butyldimethylsilyl chloride (11.22 g, 74.5 mmol) were
successively added. After stirring for 6 h at room temperature, 125 mL of water was poured and
the layers were separated, the aqueous layer was extracted with CH
combined organic phase was washed with brine, dried over MgSO
2
Cl
2
(3 x 100 mL), the
4
and concentrated under
reduced pressure. The residue was purified by flash chromatography eluting with hexanes to
1
afford 17.57 g (100%) of colourless oil. H NMR (300 MHz, CDCl
3
): δ 5.53 (s, 1H), 4.01 (s,
): δ 152.6
1
3
2
H), 1.72 (s, 3H), 0.92 (s, 9H), 0.11 (s, 9H), 0.06 (s, 6H). C NMR (75.5 MHz, CDCl
3
(
s), 120.6 (d), 68.9 (t), 25.9 (q), 18.0 (q), -0.1 (q), -5.4 (q). IR (neat): 2955, 2858, 1633, 1472,
+
1
361, 1249, 1152, 1111, 1081, 838. LRMS (m/z): 201 ([M-C H ] , 35), 133 (100). HRMS calcd.
4
9
for C
9
H21OSi
2
(M-C
4
H
)+: 201.1131, found: 201.1136.
9

S-15
Enone 11.
Me
TBDMSO
SiMe3
10
Cl
OTBDMS
O
O
SnCl , CH Cl
2
4
2
1
b
11
To a solution of 1b (113 mg, 543 µmol) in CH
70 µL, 597 µmol) and this mixture was stirred for 5 min. Then, vinyl silane 10 (148 mg, 570
µmol) in CH Cl (1.4 mL) was added via syringe over 3 min and the resulting solution was
2
Cl
2
(4.0 mL) cooled at –70ºC was added SnCl
4
(
2
2
allowed to gradually reach –20ºC over a 2 h period. The reaction was quenched when poured
into a cold (0 ºC) saturated solution of sodium potassium tartrate (8.0 mL) and this mixture was
vigorously stirred overnight. The layers were separated, the aqueous phase was extracted with
CH
2
Cl
2
(3 x 5 mL) and the combined chlorinated layers were dried (MgSO
4
), concentrated under
O/hexanes, 4:96). 135 mg (70%) of
): δ 6.46 (q, J=1.5 Hz, 1H), 4.10 (d,
reduced pressure and purified by flash chromatography (Et
2
1
light yellowish oil was isolated. H NMR (300 MHz, CDCl
3
J=1.0 Hz, 2H), 2.40 (td, J=11.5, 3.1 Hz, 1H), 2.00 (s, 3H), 1.75-1.52 (m, 6H), 1.42-1.32 (m, 1H),
.08-0.95 (m, 2H), 0.94 (s, 9H), 0.88 (d, J=6.5 Hz, 3H), 0.87 (d, J=6.8 Hz, 3H), 0.75 (d, J=6.8
1
1
3
Hz, 3H), 0.08 (s, 6H). C NMR (75.5 MHz, CDCl
3
): δ 205.4 (s), 156.1 (s), 119.4 (d), 67.0 (t),
5
5.8 (d), 44.4 (d), 38.7 (t), 34.8 (t), 32.4 (d), 28.9 (d), 25.8 (q), 24.0 (t), 22.4 (q), 21.4 (q), 18.3
(
s), 16.1 (q), 15.9 (q), -5.4 (q). IR (neat): 2955, 1684, 1626, 1463, 1258, 1118, 839. LRMS (m/z):
+
3
37 ([M-CH
3
] , 2), 213 (80), 157 (90), 83 (50), 73 (100). HRMS calcd. for C17
H
31
O
2
Si (M-
)+: 295.2093, found : 295.2097. [α]
20
= -13.9º (c 1.45, CHCl ).
C
4
H
9
D
3
Alcohol 12.
i-PrMgCl
TBAF
THF
OTBDMS
OH
OH
H
O
H
CuCN, THF
Me
O
O
O
4b
12

S-16
A 6.9 mL THF solution of the crude pivalate 4b (1.51 g, 3.4 mmol) was cooled to 0 °C and
tetrabutylammonium fluoride (1.0M solution in THF; 3.8 mL, 3.8 mmol) was added. The
mixture was allowed to stir at room temperature overnight, and 7 mL of a saturated solution of
ammonium chloride was poured. The layers were separated, the aqueous layer was extracted
Et
2
O (3 x 5 mL), the combined organic extracts were washed with brine, dried (MgSO ) and
4
concentrated in vacuo. The residue thus obtained was purified by flash chromatography eluting
1
with hexanes/EtOAc, (80:20) to give quantitatively the desired alcohol. H NMR (300 MHz,
CDCl ): δ 5.72 (dd, J=9.5, 4.0 Hz, 1H), 5.54 (dq, J=9.4, 1.2 Hz, 1H), 4.05 (s, 2H), 1.90-1.80 (m,
3
2
1
H), 1.73 (d, J=0.9 Hz, 3H), 1.71-1.60 (m, 4H), 1.55 (s, 1H), 1.30-1.19 (m, 1H), 1.18 (s, 9H),
.03-0.87 (m, 3H), 0.89 (d, J=6.6 Hz, 3H), 0.84 (d, J=6.6 Hz, 6H). 13C NMR (75.5 MHz,
CDCl
3
): δ 177.8 (s), 141.2 (s), 119.2 (d), 70.6 (d), 68.0 (t), 43.7 (d), 42.7 (d), 38.9 (s), 35.1 (t),
3
2
5.1 (t), 32.4 (d), 27.2 (q), 26.8 (d), 24.0 (t), 22.8 (q), 21.5 (q), 15.3 (q), 14.3 (q). IR (neat): 3405,
+
957, 1722, 1457, 1288, 1157, 1021, 941. LRMS (m/z): 324 (M , 5), 222 (50), 139 (55) 101
+
20
(
70), 83 (100). HRMS calcd. for C20
H
36
O
3
(M) : 324.2664, found : 324.2670. [α]
D
= -46.3º (c
0.96, CHCl3).
The cuprate reagent was first prepared by slowly adding at -15°C freshly prepared i-
propylmagnesium chloride (1.35M Et O solution; 2.6 mL, 3.6 mmol) to a suspension of 318 mg
3.6 mmoL) of CuCN in degassed THF (4.7 mL). This mixture was stirred for 25 min at -15°C,
2
(
then a 3 mL THF solution containing 115.4 mg (0.4 mmol) of the corresponding pivalate ester
was added via syringe over 10 min. The reaction mixture was immediately put at room
temperature. The reaction was monitored by TLC and it was quenched with 5 mL of a saturated
solution of NH
extracted with Et
MgSO ) and concentrated under reduced pressure. The residue was purified by flash
chromatography eluting with Et O/hexanes (15:85) to afford 93.2 mg (98%) of colourless oil.
4
Cl / NH
4
OH (9:1). The layers were separated, and the aqueous layer was
2
O (3 x 5 mL). The combined organic layers were washed with brine, dried
(
4
2
Analysis of the crude material by GC/MS showed no trace of the other diastereomer (>99% d.e.).
1
(
12): H NMR (300 MHz, CDCl
3
): δ 5.24-5.22 (m, 2H), 3.38 (d, J=6.2 Hz, 2H), 1.96-1.87 (m,
1
H), 1.83-1.68 (m, 2H), 1.65-1.53 (m, 3H), 1.43-1.33 (m, 1H), 1.22 (t, J=6.4 Hz, 1H), 1.06-0.89
(
m, 4H), 0.91 (s, 3H), 0.87 (d, J=7.0 Hz, 3H), 0.86 (d, J=6.5 Hz, 3H), 0.83 (d, J=6.9 Hz, 3H),
1
3
0
.82 (d, J=6.9 Hz, 3H), 0.69 (d, J=7.0 Hz, 3H). C NMR (75.5 MHz, CDCl ): δ 136.5 (d), 133.7
3

S-17
(
(
d), 69.2 (t), 47.0 (d), 45.5 (d), 44.3 (s), 43.8 (t), 35.1 (t), 33.2 (t), 32.5 (d), 28.4 (d), 24.0 (t), 22.6
q), 21.4 (q), 17.8 (q), 17.0 (q), 16.0 (q), 15.0 (q). IR (neat): 3416, 2953, 1671, 1456, 1371, 1029.
+
+
LRMS (m/z): 266 (M , 2), 97 (100), 81 (60). HRMS calcd. for C18
66.2603. [α]D20 = -59.1º (c 1.07, CHCl3).
H34O (M) : 266.2610, found :
2
Alcohol 13a.
i-PrMgBr
TBAF
THF
OH
H
O
H
CuCN, THF
i-Pr
O
OTBDMS
OH
O
O
7
a
13a
Same procedure as per alcohol 12, starting from pivalate 7a (3.65 g, 7.3 mmol) afforded 1.37 g
(
49%) of pure alcohol along with 665 mg (24%) of a fraction that contained a small amount of an
1
unidentified impurity that did not correspond to its diastereomer. H NMR (300 MHz, CDCl
3
): δ
7
.54-7.50 (m, 2H), 7.38-7.28 (m, 3H), 5.85 (d, J=9.9 Hz, 1H), 5.80 (dd, J=9.9, 2.2 Hz, 1H), 4.80
(
d, J=12.1 Hz, 1H), 4.30 (d, J=12.1 Hz, 1H), 3.49 (s, 1H), 1.97 (dsp, J=7.2 and 2.8 Hz, 1H), 1.96-
1
.88 (m, 1H), 1.77-1.67 (m, 3H), 1.59 (tt, J=11.6 and 2.8 Hz, 1H), 1.43-1.23 (m, 2H), 1.19 (s,
H), 1.14-0.80(m, 2H), 0.94 (d, J=6.6 Hz, 3H), 0.92 (d, J=6.6 Hz, 3H), 0.84 (d, J=7.2 Hz, 3H).
9
13C NMR (75.5 MHz, CDCl
): δ 179.1 (s), 142.2 (s), 141.4 (s), 128.4 (d), 127.7 (d), 127.3 (d),
3
1
26.3 (d), 71.2 (d), 60.4 (t), 44.0 (d), 43.5 (d), 39.2 (s), 35.4 (t), 34.9 (t), 32.8 (d), 27.1 (q), 26.4
+
(
d), 24.1 (t), 22.8 (q), 21.4 (q), 15.5 (q). IR (neat): 3447, 2954, 1708. LRMS (m/z): 386 (M , 5),
45 (60), 85 (100). HRMS calcd. for C25 : 386.2821, found: 386.2830.
1
H
38
O
3
The above alcohol (99 mg, 0.3 mmol) gave 64.6 mg (77%). Analysis of the crude material by
1
chiral HPLC showed no trace of the other diastereomer 13b (>98% d.e.). (13a) m.p. 73.5 ºC. H
NMR (300 MHz, CDCl
3
): δ 7.37-7.31 (m, 4H), 7.28-7.20 (m, 1H), 5.58 (d, J=15.9 Hz, 1H), 5.40
(
dd, J=15.9, 8.8 Hz, 1H), 3.84 (d, J=6.0 Hz, 2H), 2.36 (sept, J=6.6 Hz, 1H), 2.06 (dq, J=9.3 Hz,
1
1
H), 1.94 (dsept, J=6.6 Hz, 1H), 1.78-1.63 (m, 4H), 1.50-1.40 (m, 1H), 1.19 (t, J=6.0 Hz, 1H),
.12-0.84 (m, 3H), 0.93 (d, J=7.2 Hz, 3H), 0.91 (d, J=6.6 Hz, 3H), 0.88 (d, J=7.2 Hz, 3H), 0.77

S-18
d, J=7.7 Hz, 3H), 0.76 (d, J=7.2 Hz, 3H). C NMR (75.5 MHz, CDCl ): δ 143.3 (s), 137.5 (d),
1
3
(
3
1
3
3
29.9 (d), 128.4 (d), 128.1 (d), 126.3 (d), 67.2 (t), 52.8 (s), 47.0 (d), 46.3 (d), 43.9 (t), 35.1 (t),
2.6 (d), 31.5 (d), 28.5 (d), 23.8 (t), 22.6 (q), 21.5 (q), 18.1 (q), 17.9 (q), 15.0 (q). IR (neat):
+
557, 3434, 3019, 2956, 2843, 1599, 1455, 1036, 760. LRMS (m/z): 297 ([M-CH
3
O] , 20), 159
+
(
100), 129 (45), 84 (100). HRMS calcd. for C22
H
33 (M-CH
3
O) : 297.2582, found: 297.2576.
Alcohol 13b.
i-PrMgBr
TBAF
THF
OH
i-Pr
H
O
H
CuCN, THF
O
OTBDMS
OH
O
O
7
b
13b
Same procedure as per alcohol 12, starting from pivalate 7b. Deprotection of the silyl ether (1.81
g, 3.6 mmol) afforded 1.39 g (100%) of a colourless oil corresponding to the primary free
1
alcohol. H NMR (300 MHz, CDCl
3
): δ 7.54-7.51 (m, 2H), 7.40-7.29 (m, 3H), 5.85 (dd, J=10.4,
3
3
.9 Hz, 1H), 5.79 (d, J=10.3 Hz, 1H), 4.85 (d, J=12.6 Hz, 1H), 4.37 (dd, J=12.3, 6.1 Hz, 1H),
.37 (s, 1H), 2.05-1.92 (m, 2H), 1.86-1.67 (m, 3H), 1.43-1.34 (m, 1H), 1.22 (s, 9H), 1.11-0.83
1
3
(
m, 4H), 0.96 (d, J=6.5 Hz, 3H), 0.89 (d, J=7.0 Hz, 3H), 0.86 (d, J=7.0 Hz, 3H). C NMR (75.5
MHz, CDCl ): δ 178.9 (s), 144.2 (s), 141.1 (s), 128.4 (d), 127.7 (d), 126.5 (d), 124.5 (d), 71.8
d), 60.3 (t), 44.1 (d), 42.9 (d), 39.0 (s), 35.6 (t), 34.9 (t), 32.5 (d), 27.1 (q), 26.9 (d), 24.0 (t),
3
(
2
9
2.8 (q), 21.5 (q), 15.4 (q). IR (neat): 3497, 3056, 2966, 2866, 1713, 1456, 1285, 1172, 1023,
+
34. LRMS (m/z): 386 (M , 5), 311 (25), 284 (25), 255 (50), 145 (100), 129 (55), 117 (85), 91
+
(
90), 85 (90). HRMS calcd. for C25
H
38
O
3
(M) : 386.2821, found: 386.2811.
The cuprate reagent was prepared by adding freshly prepared i-propylmagnesium bromide (1.28
M Et O solution; 6.8 mL, 8.7 mmol) to a suspension of CuCN (781 mg, 8.7 mmol) in 17.4 mL
Et O at -15°C. Thus, 337 mg (0.9 mmol) of the corresponding pivalate ester afforded 289 mg
2
2
(
77%) of colourless oil. Analysis of the crude material by chiral HPLC showed no trace of the
1
other diastereomer (>98% d.e.). (13b): H NMR (300 MHz, CDCl
3
): δ 7.35-7.32 (m, 2H), 7.25-
7
.22 (m, 3H), 5.57 (d, J=16.2 Hz, 1H), 5.38 (dd, J=16.2, 9.0 Hz, 1H), 3.87 (d, J=11.0 Hz, 1H),

S-19
3
1
3
3
.81 (d, J=11.0 Hz, 1H), 2.48 (sept, J=6.8 Hz, 1H), 2.07-2.00 (m, 1H), 1.94 (dsp, J=7.0, 2.0 Hz,
H), 1.78-1.64 (m, 3H), 1.47-1.37 (m, 1H), 1.21 (s, 1H), 1.11-0.95 (m, 3H), 0.92 (d, J=7.4 Hz,
H), 0.90 (d, J=7.0 Hz, 3H), 0.88 (d, J=6.8 Hz, 3H), 0.82 (d, J=6.9 Hz, 3H), 0.75 (d, J=6.9 Hz,
1
3
H). C NMR (75.5 MHz, CDCl ): δ 143.2 (s), 137.8 (d), 129.6 (d), 128.4 (d), 128.1 (d), 126.2
3
(
d), 67.0 (t), 53.1 (s), 47.2 (d), 46.2 (d), 43.9 (t), 35.2 (t), 32.6 (d), 31.8 (d), 28.6 (d), 23.9 (t),
2
1
1
2.6 (q), 21.5 (q), 18.0 (q), 17.8 (q), 15.2 (q). IR (neat): 3560, 3423, 3020, 2952, 2844, 1599,
+
+
453, 1036, 759. LRMS (m/z): 310 ([M-H
29 (70), 91 (50). HRMS calcd. for C23
2
O] , 2), 297 ([M-CH
3
O] , 15), 267 (20), 159 (100),
+
H34 (M-H
2
O) : 310.2660, found: 310.2653.
Alcohol 14a.
OMe
OMe
EtMgBr
TBAF
THF
OH
H
O
H
CuCN, THF
OH
Et
O
OTBDMS
O
O
MeO
8
a
14a
Same procedure as per alcohol 12. The deprotection starting from pivalate 8a (1.86 g, 3.5 mmol)
1
afforded 1.46 g (100%) of alcohol. H NMR (300 MHz, CDCl
3
): δ 7.26 (t, J=7.7 Hz, 1H), 7.11-
7
1
.09 (m, 2H), 6.84 (dd, J=6.0, 2.2 Hz, 1H), 5.86 (d, J=9.4 Hz, 1H), 5.80 (dd, J=9.4 and 2.2 Hz,
H), 4.78 (d, J=12.1 Hz, 1H), 4.31 (d, J=12.1 Hz, 1H), 3.82 (s, 3H), 2.02-1.87 (m, 2H), 1.78-1.55
(
(
m, 3H), 1.39-1.22 (m, 3H), 1.20 (s, 9H), 1.06 (q, J=12.1 Hz, 2H), 0.95 (d, J=6.6 Hz, 3H), 0.93
1
3
d, J=6.6 Hz, 3H), 0.85 (d, J=6.6 Hz, 3H). C NMR (75.5 MHz, CDCl
3
): δ 179.0 (s), 159.6 (s),
1
42.6 (s), 142.0 (s), 129.3 (d), 127.6 (d), 118.9 (d), 112.9 (d), 112.3 (d), 71.2 (d), 60.4 (t), 55.2
(
q), 44.0 (d), 43.6 (d), 39.2 (s), 35.4 (t), 35.0 (t), 32.8 (d), 27.1 (q), 26.4 (d), 24.1 (t), 22.8 (q),
+
+
2
1.4 (q), 15.5 (q). LRMS (m/z): 416 (M , 5), 398 ([M-H
2
O] , 5), 175 (100), 147 (50). HRMS
+
calcd. for C26
H
40
O
4
(M) : 416.2926, found: 416.2931.
The above alcohol (738 mg, 1.8 mmol) was submitted to the cuprate reaction to give 528 mg
(
86%) of 14a as a colourless oil. Analysis of the crude material by chiral HPLC showed no trace
1
of 14b. (14a): H NMR (300 MHz, CDCl
3
): δ 7.25 (t, J=8.3 Hz, 1H), 6.89-6.85 (m, 2H), 6.77
(
dd, J=8.3, 2.2 Hz, 1H), 5.54 (d, J=16.0 Hz, 1H), 5.36 (dd, J=16.0, 9.4 Hz, 1H), 3.79 (s, 3H),

S-20
3
1
.84-3.72 (m, 2H), 2.04-1.57 (m, 5H), 1.82 (q, J=7.2 Hz, 2H), 1.47-1.38 (m, 1H), 1.25 (s, 1H),
1
3
.05-0.92 (m, 4H), 0.91 (t, J=7.2 Hz, 3H), 0.91 (d, J=6.6 Hz, 6H), 0.76 (d, J=6.1 Hz, 3H). C
): δ 159.5 (s), 145.8 (s), 136.7 (d), 132.7 (d), 129.1 (d), 119.8 (d), 113.9
d), 111.3 (d), 67.5 (t), 55.1 (q), 49.8 (s), 47.1 (d), 45.7 (d), 43.8 (t), 35.1 (t), 32.5 (d), 28.5 (d),
NMR (75.5 MHz, CDCl
3
(
2
1
8.4 (t), 23.9 (t), 22.6 (q), 21.4 (q), 15.2 (q), 8.5 (q). IR (neat): 3437, 2952, 2870, 1600, 1464,
+
254, 1048, 778. LRMS (m/z): 344 (M , 5), 313 (50), 175 (100), 149 (50). HRMS calcd. for
+
C
23
H
36
O
2
(M) : 344.2715 found: 344.2709.
Alcohol 14b.
OMe
OMe
EtMgBr
TBAF
THF
OH
H
O
H
CuCN, THF
Et
O
OTBDMS
OH
O
O
OMe
8
b
14b
Same procedure as per alcohol 12, starting from pivalate 8b. Deprotection of the silylated ether
(
1.86 g, 3.5 mmol) afforded 1.46 g (100%) of a colourless oil corresponding to the primary
1
alcohol. H NMR (300 MHz, CDCl
3
): δ 7.30-7.25 (m, 1H), 7.10-7.06 (m, 2H), 6.86 (dd, J=8.2,
2
3
2
.8 Hz, 1H), 5.83-5.75 (m, 2H), 4.81 (dd, J=12.7, 2.8 Hz, 1H), 4.33 (dd, J=12.7, 9.4 Hz, 1H),
.83 (s, 3H), 3.29 (dd, J=9.9, 3.3 Hz, 1H), 2.02-1.88 (m, 2H), 1.81-1.62 (m, 3H), 1.41-1.31 (m,
H), 1.19 (s, 9H), 1.07-0.91 (m, 3H), 0.93 (d, J=6.6 Hz, 3H), 0.87 (d, J=6.6 Hz, 3H), 0.84 (d,
1
3
J=7.2 Hz, 3H). C NMR (75.5 MHz, CDCl
3
): δ 179.0 (s), 159.6 (s), 144.0 (s), 142.7 (s), 129.4
(
d), 124.7 (d), 119.1 (d), 112.8 (d), 112.6 (d), 71.8 (d), 60.4 (t), 55.3 (q), 44.1 (d), 43.0 (d), 39.1
(
s), 36.0 (t), 34.9 (t), 32.5 (d), 27.1 (q), 26.9 (d), 24.0 (t), 22.8 (q), 21.6 (q), 15.4 (q). IR (neat):
+
+
3
1
442, 2956, 2919, 1710, 1644, 1480, 1286, 1168. LRMS (m/z): 416 (M , 5), 398 ([M-H
2
O] , 5),
+
75 (100), 147 (50). HRMS calcd. for C26
H
40
O
4
(M) : 416.2926, found: 416.2931.
The cuprate reagent was prepared by adding freshly prepared ethylmagnesium bromide (1.85 M
Et O solution; 0.52 mL, 1.0 mmol) to a suspension of CuCN (85.6 mg, 1.0 mmol) in 1.9 mL.
THF at -22°C. Thus, 79.6 mg (0.2 mmol) of the corresponding pivalate ester afforded 41.9 mg
64%) of yellowish oil. Analysis of the crude material by chiral HPLC showed a trace of the
2
(

S-21
other diastereomer (94% d.e.). (14b): H NMR (300 MHz, CDCl ): δ 7.28-7.22 (m, 1H), 6.90-
1
3
6
3
.86 (m, 2H), 6.79-6.75 (m, 1H), 5.52 (d, J=15.9 Hz, 1H), 5.34 (dd, J=15.9, 9.4 Hz, 1H), 3.79 (s,
H), 3.81-3.78 (m, 2H), 2.07-1.61 (m, 4H), 1.82 (q, J=7.2 Hz, 2H), 1.44-1.25 (m, 2H), 1.05-0.80
(
m, 4H), 0.89 (d, J=6.6 Hz, 3H), 0.87 (d, J=6.1 Hz, 3H), 0.78 (t, J=7.2 Hz, 3H), 0.76 (d, J=6.6
1
3
Hz, 3H). C NMR (75.5 MHz, CDCl
3
): δ 159.5 (s), 145.8 (s), 136.7 (d), 132.8 (d), 129.1 (d),
1
3
2
20.0 (d), 114.0 (d), 111.4 (d), 67.5 (t), 55.1 (q), 49.8 (s), 47.1 (d), 45.7 (d), 43.7 (t), 35.1 (t),
2.5 (d), 28.6 (d), 28.5 (t), 23.9 (t), 22.6 (q), 21.5 (q), 15.1 (q), 8.5 (q). IR (neat): 3463,
+
954,1599, 1463, 1257, 1048, 777. LRMS (m/z): 344 (M , 5), 313 (65), 175 (100), 149 (45).
+
HRMS calcd. for C23
H
36
O
2
(M) : 344.2715 found: 344.2719.
Carbamate 15.
O
O
DPPA
Ph-Me
Jones
CO H
NH
Me
2
OH
Me
Me
Et N
3
9
-FM
12
15
A solution containing 449 mg (1.7 mmol) of alcohol 12 in 17 mL acetone was cooled to 0 °C,
whereupon an excess of the Jones reagent (stock solution: 26.7g (267.0 mmol) of chromium
oxide + 23.0 mL conc. H
2
SO , diluted at 100 mL with distilled water) was transferred dropwise
4
via pipet until the reaction solution remained orange coloured. This mixture was vigorously
stirred at 0°C for 6 h. Then, a few drops of 2-propanol were added until the mixture remained
green coloured and the solvents were concentrated under reduced pressure. The green solid
residue was dissolved in water and was extracted 3 times with CH
2
Cl . The combined organic
2
layers were washed with brine, dried (MgSO ) and concentrated under reduced pressure. The
4
crude residue was purified by flash chromatography eluting with hexanes/EtOAc, (90:10) to give
1
4
02 mg (85%) of colourless oil corresponding to the carboxylic acid. H NMR (300 MHz,
CDCl
3
): δ 5.55 (d, J=15.8 Hz, 1H), 5.29 (dd, J=15.8 et 9.1 Hz, 1H), 2.12 (sept, J=6.8 Hz, 1H),
.98-1.86 (m, 1H), 1.79-1.69 (m, 2H), 1.64-1.54 (m, 2H), 1.43-1.31 (m, 1H), 1.14 (s, 3H), 1.03-
.79 (m, 4H), 0.88 (d, J=6.7 Hz, 3H), 0.86 (d, J=6.4 Hz, 3H), 0.84 (d, J=6.9 Hz, 3H), 0.83 (d,
1
0

S-22
J=6.9 Hz, 3H), 0.68 (d, J=6.9 Hz, 3H). C NMR (75.5 MHz, CDCl ): δ 183.2 (s), 135.8 (d),
1
3
3
1
31.3 (d), 51.4 (s), 47.4 (d), 45.0 (d), 43.4 (t), 35.3 (t), 34.8 (d), 32.5 (d), 28.2 (d), 24.3 (t), 22.6
(
q), 21.4 (q), 17.8 (q), 17.2 (q), 15.4 (q), 14.7 (q). IR (neat): 2929, 1701, 1456, 1386, 1277, 976,
+
7
58. LRMS (m/z): 280 (M , 30), 237 (50), 165 (55), 137 (80), 109 (85), 95 (100). HRMS calcd.
+
for C18
H
32
O
2
(M) : 280.2402, found : 280.2396.
0
.32 mL (1.5 mmol) of diphenylphosphoryl azide was added to a 14.3 mL toluene solution
containing 402 mg (1.4 mmol) of the corresponding carboxylic acid and 0.22 mL (1.6 mmol) of
triethylamine. This solution was immediately warmed to reflux for 60 min. The reaction solution
was then cooled to room temperature and a saturated solution of ammonium chloride (10 mL)
was poured, the layers were separated, the aqueous layer was extracted 3 times with Et
2
O and the
combined organic extracts were washed with brine. After being dried (MgSO ) and the solvent
4
removed under reduced pressure, the crude isocyanate was quantitatively isolated as pale yellow
oil. Then, 1.00 g (5.1 mmol) of 9-fluorenylmethanol was added and this mixture was warmed
neat at 110°C until complete consumption of the isocyanate as seen by TLC. The residue was
purified by flash chromatography using EtOAc/hexanes (10:90) as eluent to afford 520 mg
1
(
77%) of carbamate 15. (15): H NMR (300 MHz, CDCl
3
): δ 7.77 (d, J=7.4 Hz, 2H), 7.61 (d, 7.3
Hz, 2H), 7.40 (td, J=7.2 Hz, 2H), 7.32 (td, J=7.2, 0.7 Hz, 2H), 5.58-5.43 (m, 1H), 5.32-5.19 (m,
1
1
H), 4.72 (s, 1H), 4.36 (m, 2H), 4.23 (t, J=6.5 Hz, 1H), 2.22 (m, 1H), 1.95-1.53 (m, 4H), 1.45-
.27 (m, 4H), 1.06-0.75 (m, 2H), 1.00 (d, J=6.9 Hz, 3H), 0.98 (d, J=6.8 Hz, 3H), 0.96 (d, J=6.9
1
3
Hz, 3H), 0.88 (s, 3H), 0.87 (d, J=6.4 Hz, 3H), 0.68 (d, J=6.7 Hz, 3H). C NMR (75.5 MHz,
CDCl ): δ 154.5 (s), 144.2 (s), 141.3 (s), 134.3 (d), 132.0 (d), 127.5 (d), 127.0 (d), 125.0 (d),
19.9 (d), 65.9 (t), 59.0 (s), 47.4 (d), 47.2 (d), 44.8 (d), 43.4 (t), 35.1 (t), 35.1 (d), 32.5 (d), 28.1
3
1
(
d), 24.1 (t), 22.6 (q), 21.4 (q), 21.0 (q), 17.3 (q), 17.2 (q), 15.3 (q). IR (neat): 3444, 3348, 2953,
+
1
728, 1500, 1244, 1085, 757. LRMS (m/z): 474 (MH , 30), 235 (60), 208 (85), 178 (100).
+
20
HRMS calcd. for C32
CHCl3).
H44NO
2
(MH ): 474.3372, found: 474.3375. [α]
D
= -27.6º (c 1.41,

S-23
Carboxylic acid 16.
O
TBDPSCl
imidazole
O3
HO
OTBDPS
OH
OTBDPS
Me
Me
Me
Jones
12
16
To a solution of alcohol 12 (407 mg, 1.5 mmol) in CH
2
Cl (6.1 mL) was added imidazole (187
2
mg, 2.8 mmol) and t-butyldiphenylsilyl chloride (0.60 mL, 2.3 mmol). The mixture was stirred
overnight at room temperature, and water (7 mL) was added. The layers were separated, the
aqueous layer was extracted with CH
2
Cl
2
(3 x 5 mL) and the combined organic layers were
washed with brine, dried (MgSO ) and concentrated under reduced pressure. The residue was
4
purified by flash chromatography eluting with hexanes to afford 771 mg (100%) of colourless oil
1
corresponding to the protected alcohol. H NMR (300 MHz, CDCl
3
): δ 7.66-7.64 (m, 4H), 7.44-
7
1
.34 (m, 6H), 5.43 (d, J=15.9 Hz, 1H), 5.09 (dd, J=15.9, 9.0 Hz, 1H), 3.47-3.39 (m, 2H), 1.92-
.79 (m, 3H), 1.73-1.68 (m, 1H), 1.61-1.54 (m, 2H), 1.41-1.26 (m, 3H), 1.05 (s, 9H), 1.01-0.89
(
m, 2H), 0.88 (s, 3H), 0.85 (d, J=7.0 Hz, 3H), 0.83 (d, J=7.5 Hz, 3H), 0.77 (d, J=6.9 Hz, 3H),
1
3
0
.76 (d, J=6.8 Hz, 3H), 0.66 (d, J=6.9 Hz, 3H). C NMR (75.5 MHz, CDCl ): δ 135.7 (d), 133.8
3
(
d), 129.4 (d), 127.5 (d), 70.2 (t), 47.2 (d), 45.2 (d), 43.9 (t), 43.4 (s), 35.5 (t), 32.5 (d), 31.8 (d),
2
7.9 (d), 26.9 (q), 24.1 (t), 22.6 (q), 21.5 (q), 19.4 (s), 17.7 (q), 17.6 (q), 17.2 (q), 15.4 (q). IR
+
(
neat): 3071, 2957, 2855, 1588, 1469, 1111, 978, 827. LRMS (m/z): 447 ([M-C
4
H
9
] , 80), 267
+
20
(
20), 199 (100). HRMS calcd. for C H OSi (M-C H ) : 447.3083, found: 447.3087. [α] = -
3
0
43
4
9
D
2
8.1º (c 1.35, CHCl
3
).
7
70 mg (1.5 mmol) of the protected alcohol was dissolved in 30.0 mL acetone/CH
2
Cl
2
(1:1) and
cooled at –78 ºC. An ozone stream (6.5 PSI, 1.5 LPM of oxygen; 90V) was bubbled through the
solution until a fade blue colour remained (2-15 min) and no starting material left by TLC
analysis. Nitrogen was introduced to purge the system for 5 min. The intermediate ozonide was
oxidized straight to the corresponding carboxylic acid (16) by adding Jones reagent directly to
the mixture (same treatment as for the oxidation of primary alcohol previously described, see
formation of 15). In this manner, 570 mg (97%) of yellowish oil was isolated along with 242 mg
(
86%) of the chiral auxiliary after purification by flash chromatography eluting with CH
2
Cl .
2

S-24
16): H NMR (300 MHz, CDCl ): δ 7.68-7.63 (m, 4H), 7.44-7.36 (m, 6H), 3.83 (d, J=9.6 Hz,
1
(
3
1
H), 3.59 (d, J=9.6 Hz, 1H), 2.09 (sept, J=6.9 Hz, 1H), 1.13 (s, 3H), 1.04 (s, 9H), 0.87 (d, J=6.9
1
3
Hz, 3H), 0.77 (d, J=6.9 Hz, 3H). C NMR (75.5 MHz, CDCl ): δ 180.7 (s), 135.7 (d), 133.0 (s),
3
1
29.8 (d), 127.7 (d), 68.8 (t), 51.8 (s), 31.3 (d), 26.8 (q), 19.3 (s), 18.3 (q), 17.0 (q), 13.9 (q). IR
+
(
neat): 3074, 2962, 1700, 1471, 1428, 1262, 1111, 1086, 701. LRMS (m/z): 327 ([M-C
0), 199 (100). HRMS calcd. for C19 Si (M-C
)+: 327.1416, found: 327.1410.
4
H
9
] ,
5
H
23
O
3
4
H
9
Protected amino acid (S)-17.
O
O
O
O
a) O , DMS
O
3
NH
Me
NH
Me
HO
b) NaClO , t-BuOH
2
2
-methyl-2-butene
NaHPO
3
15
(S)-17
3
7
97 mg (0.8 mmol) of the carbamate 15 was dissolved in 4.2 mL CH
2
Cl
2
and was cooled to –
8°C. An ozone stream (6.5 PSI, 1.5 LPM of oxygen; 75V) was bubbled through the solution
until a fade blue colour remained and no starting material left by TLC analysis. Nitrogen was
introduced to purge the system for 5 min and methyl sulfide (1.0 mL, 13.6 mmol) was added.
The reaction was allowed to warm slowly to room temperature on a 1 h period and it was stirred
for an additional 5 h, whereupon the solvent was removed in vacuo to afford a solid residue
which was used as such for the next oxidation step. A pure sample could be purified by flash
chromatography eluting with Et
2
O/toluene (7:93). An enantiomeric excess of 90% was found by
): δ 9.48 (s, 1H), 7.86 (d, J=7.2 Hz, 2H),
1
chiral HPLC analysis. H NMR (300 MHz, acetone-d
6
7
2
.69 (d, J=7.7 Hz, 2H), 7.41 (t, J=7.4 Hz, 2H), 7.32 (t, J=7.4 Hz, 2H), 6.85 (s, 1H), 4.43-4.31 (m,
H), 4.22 (t, J=6.6 Hz, 1H), 2.12-2.04 (m, 1H), 1.24 (s, 3H), 0.96 (d, J=6.6 Hz, 3H), 0.93 (d,
1
3
J=7.2 Hz, 3H). C NMR (75.5 MHz, acetone-d
6
): δ 202.3 (d), 156.9 (s), 145.1 (s), 142.2 (s),
1
1
28.6 (d), 128.0 (d), 126.1 (d), 120.9 (d), 67.0 (t), 65.3 (s), 48.1 (d), 34.0 (d), 17.3 (q), 17.3 (q),
7.3 (q). IR (neat): 3341, 2964, 2877, 1713, 1511, 1453, 1255, 1105, 1041. LRMS (m/z): 355
+
+
+
([MNH
4
] , 5), 338 (MH , 100), 178 (50). HRMS calcd. for C21
H24NO
3
(MH) : 338.1756, found:
3
38.1764.

S-25
A 3.5 mL solution of t-butanol containing the corresponding crude aldehyde (0.8 mmol) and 2.0
mL (18.4 mmol) of 2-methyl-2-butene was prepared. To this solution was added an aqueous
solution (3.5 mL of water) containing sodium chlorite (152 mg, 1.7 mmol) and sodium
dihydrogenophosphate (231 mg, 1.7 mmol). This mixture was vigorously stirred overnight at
room temperature. The solvents were removed under reduced pressure and brine (3 mL) was
then added. The aqueous mixture was extracted with CH
organic layers were dried over MgSO , concentrated under reduced pressure and purified by
, 5:95). In this way, 164 mg (55%, 2 steps) of white foam
2
Cl
2
(3 x 5 mL) and the combined
4
flash chromatography (MeOH/ CH
2
Cl
2
was isolated.
Spectroscopic data is identical to compound (R)-17. [α] 20
= +5.8º (c 1.05, CHCl ).
D
3
Protected amino acid (R)-17.
O
DPPA
Ph-Me
a) TBAF
b) Jones'
O
O
O
O
HO
OTBDPS
O
Me
Et N
HN
HN
3
OTBDPS
OH
9
-FNM
Me
Me
1
6
(R)-17
5
67 mg (1.5 mmol) of the carboxylic acid 16 was dissolved in 14.7 mL toluene with 0.23 mL
1.6 mmol) of trietylamine. Then, 0.33 mL (1.6 mmol) of diphenylphosphoryl azide was added
and the solution was heated under reflux for 2 h. The reaction was neutralized by adding water
10 mL). The layers were separated, the aqueous layer was extracted with Et O (3 x 8 mL) and
the combined organic layers were washed with brine, dried (MgSO ) and concentrated under
(
(
2
4
reduced pressure to afford quantitatively the isocyanate as pale yellow oil. Then, 1.00 g (5.1
mmol) of 9-fluorenylmethanol was added and this mixture was warmed neat at 110°C until
complete consumption of the isocyanate as seen by TLC. The residue was purified by flash
chromatography using EtOAc/hexanes (10:90) as eluent to afford 676 mg (79%) of the
1
corresponding carbamate. H NMR (300 MHz, CDCl
3
): δ 7.79-7.65 (m, 8H), 7.47-7.26 (m,
1
0H), 5.09 (s, 1H), 4.33 (s, 2H), 4.26-4.23 (m, 1H), 3.76-3.66 (m, 2H), 2.37-2.34 (m, 1H), 1.28
1
3
(
s, 3H), 1.11 (s, 9H), 0.93 (d, J=4.8 Hz, 3H), 0.87 (d, J=6.0 Hz, 3H). C NMR (75.5 MHz,
CDCl ): δ 154.9 (s), 144.2 (s), 144.1 (s), 141.3 (s), 135.6 (d), 133.2 (s), 129.8 (d), 127.7 (d),
3

S-26
1
1
1
27.6 (d), 127.0 (d), 125.1 (d), 119.9 (d), 66.3 (t), 66.1 (t), 59.2 (s), 47.4 (d), 32.2 (d), 26.9 (q),
9.4 (s), 17.6 (q), 17.3 (q), 17.1 (q). IR (neat): 3424, 3365, 3067, 2959, 2859, 1727, 1503, 1249,
108, 1086, 821. LRMS (m/z): 520 ([10), 342 (20), 199 (80), 179 (100), 165 (25). HRMS calcd.
)+: 520.2308, found: 520.2297. [α]
20
= +7.1º (c 1.12, CHCl ).
for C33
H34NO
3
Si (M-C
4
H
9
D
3
A solution of 482 mg (0.8 mmol) of the corresponding carbamate in 16.7 mL THF was stirred at
room temperature while a commercial solution of hydrogen fluoride-pyridine was added (1.5
mL). The reaction was stirred for 6 h, and then it was quenched by slowly adding 20 mL of a
saturated solution of sodium bicarbonate. The mixture was extracted with EtOAc (4 x 10 mL)
and the combined organic layers were dried over MgSO , concentrated under reduced pressure
4
and purified by flash chromatography eluting with EtOAc/hexanes (30:70). 284 mg (100%) of
1
yellowish solid was isolated. H NMR (300 MHz, CDCl
3
): δ 7.77 (d, J=7.5 Hz, 2H), 7.59 (d,
J=7.4 Hz, 2H), 7.41 (t, J=7.4 Hz, 2H), 7.32 (t, J=7.4 Hz, 2H), 4.78 (s, 1H), 4.46-4.37 (m, 2H),
.20 (t, J=6.4 Hz, 1H), 4.09 (s, 1H), 3.73-3.65 (m, 2H), 2.34-2.22 (m, 1H), 1.02 (s, 3H), 0.92 (d,
4
1
3
J=6.6 Hz, 3H), 0.87 (d, J=6.7 Hz, 3H). C NMR (75.5 MHz, CDCl
3
): δ 156.4 (s), 143.8 (s),
41.2 (s), 127.7 (d), 127.0 (d), 124.9 (d), 120.0 (d), 68.1 (t), 66.3 (t), 60.2 (s), 47.3 (d), 31.1 (d),
8.2 (q), 17.2 (q), 16.7 (q). IR (neat): 3405, 3329, 2959, 1691, 1510, 1263, 1033. LRMS (m/z):
1
1
3
+
+
39 (M , 1), 308 ([M-OMe] ,10), 196 (20), 178 (100), 165 (75). HRMS calcd. for
+
C
20
H22NO
2
(M-OMe) : 308.1650, found: 308.1646.
The corresponding primary alcohol (280 mg, 0.8 mmol) was dissolved in acetone (8.3 mL) and
cooled to 0 ºC. Then, a large excess of Jones reagent was added via pipet until a dark orange
colour persisted. The mixture was allowed to stir at room temperature for 3 h, whereupon a few
drops of 2-propanol were added until the mixture remained green coloured. The solvents were
removed under reduced pressure, the green solid residue was solubilized in a minimum of water
and it was extracted with CH
2
Cl
2
(4 x 10 mL). The combined organic extracts were alternatively
and concentrated under reduced pressure. The
washed with water and brine, dried over MgSO
4
residue was purified by flash chromatography eluting with MeOH / CHCl
3
(2:98) to afford 243
1
mg (83%) of a white foam. (R)-17: H NMR (300 MHz, DMSO-d
6
): δ 12.26 (s, 1H), 7.88 (d,
J=7.4 Hz, 2H), 7.73 (d, J=7.4 Hz, 2H), 7.41 (t, J=7.4 Hz, 2H), 7.32 (t, J=7.4 Hz, 2H), 4.23-4.17
m, 3H), 2.01 (sept, J=6.7 Hz, 1H), 1.28 (s, 3H), 0.91 (d, J=6.7 Hz, 3H), 0.85 (d, J=6.8 Hz, 3H).
13C NMR (75.5 MHz, DMSO-d
): δ 174.9 (s), 155.4 (s), 143.9 (s), 140.7 (s), 127.7 (d), 127.1 (d),
25.4 (d), 120.1 (d), 65.5 (t), 61.9 (s), 48.6 (d), 33.8 (d), 17.5 (q), 17.2 (q). IR (neat): 3328, 3065,
(
6
1

S-27
+
]+, 3),
(M+):
2
3
3
965, 1712, 1503, 1450, 1342, 1250, 1105, 1077. LRMS (m/z): 353 (M , 1), 310 ([M-C
3
H
7
+
08 ([M-CO
2
H] , 5), 196 (90), 178 (100), 115 (80), 87 (50). HRMS calcd. for C21
H23NO
4
2
0
53.1627, found: 353.1637. [α]
D
= -8.5 º (c 0.82, CHCl ).
3
Amino acid (S)-18.
Jones
OH
CO H
2
Ph i-Pr
Ph i-Pr
13b
2
20 mg (0.7 mmol) of alcohol 13b was treated as per alcohol 12 to give 188 mg (82%) of a
carboxylic acid as a white solid after purification by flash chromatography (EtOAc/hexanes,
1
1
0:90). H NMR (300 MHz, CDCl
3
): δ 7.37-7.23 (m, 5H), 5.78 (d, J=16.0 Hz, 1H), 5.39 (dd,
J=16.0, 9.4 Hz, 1H), 2.83 (sept, J=6.7 Hz, 1H), 2.08-1.99 (m, 1H), 1.85 (dsept, J=6.9, 0.9 Hz,
H), 1.75-1.59 (m, 3H), 1.46-1.36 (m, 1H), 1.27-0.94 (m, 4H), 0.90 (d, J=6.7 Hz, 3H), 0.89 (d,
1
1
3
J=6.5 Hz, 3H), 0.86 (d, J=7.1 Hz, 3H), 0.83 (d, J=6.8 Hz, 3H), 0.74 (d, J=6.9 Hz, 3H). C NMR
75.5 MHz, CDCl ): δ 180.4 (s), 140.3 (s), 139.8 (d), 128.9 (d), 127.8 (d), 127.1 (d), 126.8 (d),
0.9 (s), 47.1 (d), 46.0 (d), 43.2 (t), 35.1 (t), 32.5 (d), 32.4 (d), 28.3 (d), 24.0 (t), 22.6 (q), 21.4
(
3
6
(
(
q), 18.7 (q), 18.2 (q), 15.1 (q). IR (neat): 3026, 2957, 2873, 1698, 1445, 1267, 983. LRMS
+
m/z): 342 (M , 20), 299 (95), 253 (30), 163 (75), 137 (75), 115 (100). HRMS calcd. for
+
C
23
H
34
O
2
(M) : 342.2559, found: 342.2547.
O
O
DPPA
Ph-Me
CO H
NH
Ph i-Pr
2
Ph i-Pr
Et N
3
9
-FM
The above carboxylic acid was submitted to the Curtius rearrangement according to the
procedure used to make 15. However, the crude isocyanate was dissolved in 1.25 mL benzene

S-28
and 9.3 µL (31.4 µmol) of titanium tetraisopropoxide was added to catalyze the addition of 9-
fluorenemethanol (123 mg, 0.6 mmol) under reflux. Thus, starting with 107.4 mg (0.3 mmol) of
the corresponding carboxylic acid gave 99.6 mg (59%) of a white foam after purification by flash
1
chromatography (Et
2
O/toluene, 2:98). H NMR (300 MHz, acetone-d
6
): δ 7.84 (d, J=7.2 Hz, 2H),
7
1
1
3
3
1
.70-7.66 (m, 2H), 7.44 (d, J=7.7 Hz, 2H), 7.43-7.17 (m, 7H), 6.64 (s, 1H), 6.03 (d, J=15.9 Hz,
H), 5.48 (dd, J=15.4, 9.4 Hz, 1H), 4.28-4.07 (m, 3H), 2.51-2.43 (m, 1H), 2.14-1.98 (m, 2H),
.72-1.67 (m, 2H), 1.58-1.55 (m, 1H), 1.42-1.39 (m, 1H), 1.03-0.79 (m, 4H), 0.83 (d, J=9.4 Hz,
H), 0.80 (d, J=6.6 Hz, 3H), 0.75 (d, J=7.2 Hz, 3H), 0.71 (d, J=7.2 Hz, 3H), 0.70 (d, J=7.2 Hz,
1
3
H). C NMR (75.5 MHz, acetone-d
29.7 (d), 128.6 (d), 128.3 (d), 128.3 (d), 128.0 (d), 127.1 (d), 126.2 (d), 120.9 (d), 66.6 (t), 65.5
s), 48.3 (d), 46.3 (d), 44.4 (t), 37.8 (d), 36.0 (t), 33.4 (d), 28.5 (d), 24.7 (t), 23.1 (q), 21.9 (q),
6
): δ 155.2 (s), 145.4 (s), 145.2 (s), 142.1 (s), 136.7 (d),
(
1
1
8.3 (q), 18.3 (q), 15.7 (q). IR (neat): 3439, 2953, 2918, 1687, 1633, 1492, 1444, 1331, 1227,
+
H
]+, 30), 296 (40), 179 (85), 165 (85), 158 (100).
101. LRMS (m/z): 535 (M , 2), 492 ([M-C
3
7
+
HRMS calcd. for C37
H45NO
2
(M) : 535.3450, found : 535.3438.
O
O
O
O
O
a) O , DMS
3
NH
NH
HO
b) NaClO , t-BuOH
2
Ph i-Pr
Ph i-Pr
2-methyl-2-butene
NaHPO3
(
S)-18
Same procedure as for N-protected amino acid (S)-17, starting from 13b. 96.8 mg (0.2 mmol) of
the corresponding carbamate afforded 55.2 mg (76%) of the intermediate aldehyde after
purification by Et O/toluene (3:97). An enantiomeric excess of 98% was found by chiral HPLC
2
analysis. Spectroscopic data were identical to its enantiomer (see below). 20.6 mg (47.8 µmol) of
the corresponding aldehyde afforded 15.1 mg (73%) of the corresponding amino acid after
1
purification by flash chromatography (MeOH/CH
2
Cl
2
, 3:97). (S)-18: H NMR (300 MHz,
DMSO-d ): δ 12.72 (s, 1H), 7.89 (d, J=7.2 Hz, 2H), 7.75-7.73 (m, 3H), 7.49-7.20 (m, 8H), 4.24-
6
1
3
4
.21 (m, 3H), 2.55-2.49 (m, 1H), 0.81 (d, J=6.6 Hz, 3H), 0.77 (d, J=6.6 Hz, 3H). C NMR (75.5
MHz, DMSO-d ): δ 172.8 (s), 155.1 (s), 143.8 (s), 140.7 (s), 139.4 (s), 127.7 (d), 127.3 (d),
6

S-29
1
3
26.5 (d), 125.4 (d), 120.1 (d), 68.1 (d), 65.5 (t), 46.8 (d), 35.2 (d), 17.9 (q). IR (neat): 3394,
062, 2966, 1718, 1494, 1246, 1023.
Protected amino acid (R)-18.
Jones
CO H
2
OH
i-Pr Ph
3a
i-Pr Ph
1
2
82 mg (0.9 mmol) of alcohol 13a gave 221 mg (75%) of a carboxylic acid as a colourless oil
1
after purification by flash chromatography (EtOAc/hexanes, 10:90). H NMR (300 MHz,
CDCl
3
): δ 11.36 (s, 1H), 7.37-7.24 (m, 5H), 5.77 (d, J=15.9 Hz, 1H), 5.38 (dd, J=15.9, 9.4 Hz,
H), 2.79 (sept, J=6.6 Hz, 1H), 2.07-1.97 (m, 1H), 1.82 (d, J=7.2 Hz, 1H), 1.74-1.58 (m, 3H),
.42-1.34 (m, 1H), 1.07-0.78 (m, 4H), 0.89 (d, J=6.6 Hz, 3H), 0.87 (d, J=6.6 Hz, 3H), 0.86 (d,
1
1
1
3
J=6.6 Hz, 3H), 0.82 (d, J=6.6 Hz, 3H), 0.74 (d, J=7.1 Hz, 3H). C NMR (75.5 MHz, CDCl
3
): δ
1
3
79.9 (s), 140.1 (d), 129.0 (d), 127.7 (d), 127.5 (d), 126.8 (d), 60.9 (s), 47.1 (d), 45.9 (d), 43.3 (t),
5.1 (t), 32.6 (d), 32.6 (d), 28.3 (d), 23.9 (t), 22.6 (q), 21.4 (q), 18.7 (q), 18.3 (q), 15.1 (q). IR
+
H
]+, 100),
(
neat): 3059, 2957, 1697, 1446, 1265, 759. LRMS (m/z): 342 (M , 35), 300 ([M-C
3
7
+
1
63 (60), 137 (50). HRMS calcd. for C23
H
34
O
2
(M) : 342.2559, found: 342.2564.
O
O
DPPA
Ph-Me
CO H
NH
i-Pr Ph
2
i-Pr Ph
Et N
3
9
-FM
The above carboxylic acid was submitted to the Curtius rearrangement according to the
procedure used to make 15. However, the crude isocyanate was dissolved in 0.60 mL THF and
4
.6 µL (15.5 µmol) of titanium tetraisopropoxide was added to catalyze the addition of 9-
fluorenemethanol (45.3 mg, 0.2 mmol) under reflux. Thus, starting with 52.7 mg (0.2 mmol) of

S-30
the corresponding carboxylic acid gave 60.8 mg (74%) of white foam after purification by flash
1
chromatography (Et
2
O/toluene, 2:98). H NMR (300 MHz, acetone-d
6
): δ 7.84 (d, J=7.7 Hz, 2H),
7
9
1
.68-7.66 (m, 2H), 7.46-7.19 (m, 9H), 6.61 (s, 1H), 6.01 (d, J=15.9 Hz, 1H), 5.51 (dd, J=15.9,
.4 Hz, 1H), 4.22-4.18 (m, 3H), 2.53-2.49 (m, 1H), 2.11-2.04 (m, 1H), 2.00 (sept, J=7.2 Hz, 1H),
.72-1.59 (m, 4H), 1.41-1.31 (m, 1H), 1.04-0.87 (m, 3H), 0.87 (d, J=6.0 Hz, 3H), 0.85 (d, J=7.2
1
3
Hz, 3H), 0.82 (d, J=6.1 Hz, 3H), 0.81 (d, J=6.6 Hz, 3H), 0.74 (d, J=7.2 Hz, 3H). C NMR (75.5
MHz, acetone-d ): δ 155.3 (s), 145.3 (s), 144.3 (s), 142.1 (s), 136.6 (d), 130.4 (d), 128.6 (d),
28.4 (d), 128.0 (d), 127.1 (d), 126.3 (d), 120.9 (d), 66.6 (t), 65.7 (s), 48.2 (d), 46.3 (d), 44.4 (t),
6
1
3
7.6 (d), 36.0 (t), 33.4 (d), 29.0 (d), 24.7 (t), 23.0 (q), 22.0 (q), 18.3 (q), 18.3 (q), 15.7 (q). IR
+
(
neat): 3442, 3288, 3019, 2955, 1736, 1696, 1494, 1448, 1234, 757. LRMS (m/z): 535 (M , 2),
]+, 55), 179 (85), 178 (100). HRMS calcd. for C37
H45NO
(M) : 535.3450, found :
+
4
5
92 ([M-C
35.3454.
3
H
7
2
O
O
O
O
O
a) O , DMS
3
NH
NH
i-Pr Ph
HO
b) NaClO , t-BuOH
2
i-Pr Ph
2-methyl-2-butene
NaHPO3
(
R)-18
Same procedure as for N-protected amino acid (S)-17 but starting from 13a. 125.1 mg (0.2
mmol) of the corresponding carbamate afforded 61.3 mg (66%) of the intermediate aldehyde
after purification by Et
2
O/toluene (3:97). An enantiomeric excess of >99% was found by chiral
): δ 9.58 (s, 1H), 7.89-7.85 (m, 2H), 7.74-7.73
1
HPLC analysis. H NMR (300 MHz, acetone-d
6
(
m, 2H), 7.50-7.27 (m, 9H), 4.42 (d, J=6.4 Hz, 2H), 4.26 (t, J=6.4 Hz, 1H), 2.69 (sept, J=6.6 Hz,
1
3
1
H), 0.98 (d, J=6.6 Hz, 3H), 0.79 (d, J=6.6 Hz, 3H). C NMR (75.5 MHz, acetone-d
6
): δ 198.4
(
d), 157.3 (s), 145.1 (s), 142.3 (s), 138.5 (s), 129.2 (d), 128.7 (d), 128.4 (d), 128.1 (d), 126.2 (d),
1
1
21.0 (d), 72.0 (s), 67.3 (t), 48.3 (d), 35.6 (d), 17.9 (q), 17.5 (q). IR (neat): 3342, 2063, 2965,
+
+
720, 1497, 1247. LRMS (m/z): 399 ([M] , 1), 370 ([M-CHO] , 50), 178 (100), 165 (90), 148
+
(
60).. HRMS calcd. for C26
H25NO
3
(M) : 399.1834, found: 399.1827.