Direct, catalytic synthesis of carbapenams via cycloaddition/rearrangement cascade reaction: Unexpected acetylenes' structure effect

Article abstract of DOI:10.1021/jo101355h

Reactions of acetylenes derived from glyceraldehyde and propargyl aldehyde show remarkable reactivity in Kinugasa cycloaddition/rearrangement cascade process catalyzed by Cu(I) ion. Reactions proceed by formation of a rigid dinuclear copper(I) complex in which each copper ion is coordinated to one or both oxygen atoms in the acetylene molecule and to both triple bonds. It has been demonstrated that one oxygen atom can be replaced by the phenyl ring, which is able to coordinate the copper ion by the aromatic sextet. Kinugasa reactions that proceed in a high yield can also be performed in the presence of a catalytic amount of the copper salt to provide products in an acceptable yield without a decrease of diastereoselectivity.

Full text of DOI:10.1021/jo101355h

Direct, catalytic synthesis of carbapenams via
cycloaddition/rearrangement cascade reaction: unexpected acetylenes’
structure effect
Adam Mames, Sebastian Stecko, Paulina Mikołajczyk, Magdalena Soluch, Bartłomiej Furman, Marek
Chmielewski*
Institute of Organic Chemistry, Polish Academy of Sciences
Kasprzaka 44/52, 01ꢀ224 Warsaw Poland
chmiel@icho.edu.pl
Supporting Materials
Part 1: experimental procedures and spectra data
Contents:
1. Synthesis of nitrones……………………………………………………………………………..S2
2. Synthesis of acetylenes 2, 6-13…………………………………………………………………S2
S1

1. Synthesis of nitrones
Nitrones 1, ent-1 and 20 were prepared according to Brandi’s protocol.1
2. Synthesis of acetylenes.
Acetylene 3 was purchased from Aldrich. Acetylenes 23a and 23b were obtained from
commercially available (R)ꢀ1ꢀphenylꢀ2ꢀpropynꢀ1ꢀol (Aldrich) and (S)ꢀ3ꢀbutynꢀ2ꢀol (Aldrich) using
standard silylation protocol.
(S)-4-ethynyl-2,2-dimethyl-1,3-dioxolane (2):2
A solution of D
ꢀglyceraldehyde acetonide3 (1.03 g, 7.90 mmol) and the Bestmann–Ohira
reagent4 (2.42 g, 12.6 mmol) in methanol (50 mL) was cooled to 0 ºC. Anhydrous potassium carbonate
(2.33 g, 16.8 mmol) was gradually added (30 min). The mixture was stirred for 12 h, allowing it to warm
to room temperature. Saturated aqueous ammonium chloride (50 mL) was added and the aqueous
solution was extracted with pentane (50 mL). The organic layer was separated, dried over magnesium
sulfate, and the solvent carefully evaporated under reduced pressure (650 mbar, bath 35 ºC). After
purification by flashꢀcolumn chromatography (eluent pentane/diethyl ether 10:1), alkyne 2 (820 mg, 6.50
mmol; 82%) was isolated as a colourless oil. [α]D +40 (c 1.0, CH2Cl2) [lit.2 +40.6 (c 1.1, CHCl3)]; IR (film)
ν: 2120, 1068 cmꢀ1; 1H NMR (200 MHz; CDCl3) δ: 4.67 (1H, ddd, J 6.4, 6.2, 2.3 Hz, Hꢀ3), 4.14 (1H, dd, J
8.1, 6.4 Hz, Hꢀ4a), 3.92 (1H, dd, J 8.1, 6.2 Hz, Hꢀ4b), 2.47 (1H, d, J 2.3 Hz, Hꢀ1), 1.47 (3H, s, Me), 1.35
(3H, s, Me); 13C NMR (50 MHz, CDCl3) δ: 110.7, 81.6, 74.3, 70.0, 65.5, 26.4 26.3; Anal. Calcd for
C7H10O2: C, 66.65; H, 7.99. Found: C, 66.59; H, 8.03.
1 Cicchi, S.; Höld, I.; Brandi, A. J. Org. Chem. 1993, 58, 5274ꢀ5275.
2 Pietruszka, J.; Witt, A. J. Chem. Soc., Perkin. Trans. 1 2000, 4293ꢀ4300.
3 Schmid, C.; Bryant, J. Org. Synth. 1995, 72, 6ꢀ10.
4 Pietruszka, J.; Witt, A. Synthesis 2006, 4266ꢀ4268.
S2

3-(2-Methoxypropan-2-yloxy)prop-1-yne (6):
Trifluoromethanesulfonic acid (130 ꢁL, 0.2 g, 1.78 mmol) was added to a cooled to 0 ºC solution
of propargyl alcohol (2.1 mL, 2.0 g, 35.7 mmol) and 2ꢀmethoxypropene (10 mL) and reaction mixture
was stirred overnight at room temperature under inert atmosphere. After neutralization with solid
K2CO3, and flitration through Celite pad, solvent and volatile reagents were removed under diminished
pressure and residue distilled (50 mmHg, 70ꢀ75ºC) to yield 4.1 g (89 %) of acetylene 6 as a colourless
oil. 1H NMR (200 MHz, CDCl3) δ: 3.93 (2H, d, J 2.2 Hz, Hꢀ3), 3.05 (3H, s, Me), 2.15 (1H, d, J 2.2 Hz,Hꢀ
1), 1.26 (6H, s, 2xMe); 13C NMR (50 MHz, CDCl3) δ: 101.9, 80.9, 73.9, 51.1, 49.5, 24.7(2x); Anal. Calcd
for C7H12O2: C, 65.60; H, 9.44. Found: C, 65.58; H, 9.46.
3-(Methoxymethoxy)prop-1-yne (7):
A solution of propargyl alcohol (0.50 g, 530 ꢁL, 8.93 mmol) and iꢀPrNEt2 (3.46 g, 4.7 mL, 26.73
mmol) in 40 mL of dry CH2Cl2 was cooled to ꢀ15ºC and a solution of MOMCl (1.07 g, 1.0 mL, 13.36
mmol) in 10 mL of CH2Cl2 was added dropwise. A cooling bath was removed and reaction mixture was
stirred overnight at room temperature under inert atmosphere. Then mixture was diluted with 50 mL of
CH2Cl2 followed by addition of 50 mL of H2O. After separation of phases, aqueous one was washed with
additional portion of CH2Cl2 (10 mL). Combined organic phases were washed with 5% HCl (15 mL), sat.
NaHCO3 (20 mL), water (10 mL) and brine (10 mL) and finally dried over MgSO4. After removal of
solvent the residue was distilled under diminished pressure (80 ºC, 12 mmHg) to yield 0.67 g (75 %) of
acetylene 8 as a colourless oil. 1H NMR (200 MHz, CDCl3) δ: 4.61 (2H, s, OCH2OMe), 4.3 (2H, d, J 2.5
Hz, Hꢀ3), 3.32 (3H, s, MeO), 2.31 (1H, d, J 2.5 Hz, Hꢀ1); 13C NMR (50 MHz, CDCl3) δ: 94.9, 79.5, 74.6,
55.5, 54.1; Anal. Calcd for C5H8O2: C, 59.98; H, 8.05. Found: C, 60.00; H, 8.03.
3-(1-Ethoxyethoxy)prop-1-yne (8):
Trifluoromethanesulfonic acid (130 ꢁL, 0.2 g, 1.78 mmol) was added to a cooled to 0 ºC solution
of propargyl alcohol (2.1 mL, 2.0 g, 35.7 mmol) in ethyl vinyl ether (10 mL) and reaction mixture was
S3

stirred overnight at room temperature under inert atmosphere. After neutralization with solid K2CO3, and
flitration through Celite pad, solvent and volatile reagents were removed under diminished pressure and
1
residue distilled by bulbꢀtoꢀbulb distillation to yield 3.9 g (86 %) of acetylene 7 as a colourless oil. H
NMR (200 MHz, CDCl3) δ: 4.84 (1H, q, CH3CHOEt), 4.21 (2H, m, Hꢀ3), 3.62 (2H, m, CH3CH2O), 2.39
(1H, m, Hꢀ1), 1.35 (3H, d, CH3CHOEt), 1.21 (3H, t, CH3CH2O); 13C NMR (50 MHz, CDCl3) δ: 98.2, 79.8,
73.7, 60.4, 53.1, 19.3, 14.9; Anal. Calcd for C7H12O2: C, 65.60; H, 9.44. Found: C, 65.58; H, 9.46.
(S)-3,4-dibenzyloxybut-1-yne (9): Acetylene 9 was prepared in twoꢀstep sequence as shown below:5
A solution of acetylene 2 (5.0 mmol, 0.63 g) in MeOH (15 mL) containing pꢀTsOHꢀH2O (48 mg,
0.25 mmol) was stirred at room temperature overnight. After evaporation of the solvent, the residue was
dissolved in CH2Cl2 (50 mL), washed with sat. aq. NaHCO3 (2x5 mL) and dried over anhydr. Na2SO4.
After evaporation of solvent, the residue was chromatographed (silica gel, AcOEt/hexane 3:2) to give
0.39 g (91%) diol as a colourless crystals.
A solution of diol (0.3 g, 3.5 mmol) in THF (5 mL) was added to a suspension of NaH (55 % in
oil, 0.37 g, 8.4 mmol) in THF (15 mL) with stirring at 0 °C. After 10 min, BnBr (1.0 mL, 1.44 g, 8.4 mmol)
and nꢀBu4NI (129 mg, 0.35 mmol) were added to the mixture at 0 °C. After 1.5 h at RT, the reaction was
quenched with water at 0 °C, and the mixture was extracted with EtOAc. The combined organic layers
were washed with brine prior to drying and solvent evaporation. Purification by column chromatography
on silica gel (hexane/EtOAc 50:1) yielded 9 (0.75 g, 80%) as a colorless oil. [α]D = +78 (c 1.3, CH2Cl2)
1
[lit.5 +76 (c 1.0, CHCl3)]; H NMR (500 MHz, CDCl3) δ: 7.39ꢀ7.26 (10H, m), 4.83 (1H, d, J 12.2 Hz,
PhCH2O), 4.65ꢀ4.55 (3H, m, PhCH2O), 4.36 (1H, ddd, J 6.7, 4.3, 1.8 Hz, Hꢀ3), 3.73 (1H, dd, J 11.0,
13
6.7 Hz, Hꢀ4a), 3.69 (1H, dd, J 11.0, 4.3 Hz, Hꢀ4b), 2.49 (1H, d, J 1.8 Hz, Hꢀ1); C NMR (125 MHz,
CDCl3) δ: 138.0, 137.6, 128.37 (2C), 128.36 (2C), 128.0 (2C), 127.8, 127.70 (2C), 127.65, 80.4, 74.9,
73.5, 72.3, 70.8, 68.2; IR (film) ν: 2114, 1097 cmꢀ1; Anal. Calcd for C18H18O2: C, 81.17; H, 6.81. Found:
C, 81.14; H, 6.79.
3-Methoxyprop-1-yne (10):
5 Kojima, N.; Maezaki, N.; Tominaga, H.; Asai, M.; Yanai, M.; Tanaka, T. Chem. Eur. J. 2003, 9, 4980ꢀ4990.
S4

To a mixture of propargyl alcohol (1.68 g, 1.7 mL, 30 mmol) and H2O (1.3 mL) was added a
50% aq solution of NaOH (3.30 g), and the mixture was stirred with a magnetical stirrer. Then dimethyl
sulfate (2.25 g, 1.7 mL, 17.8 mmol) was added dropwise keeping the temperature below 60 °C. After
stirring at 50–60 °C for 2 h, micro distillation gave a product that came over at 61–62 °C, which was
dried (CaCl2) overnight. Finally, reꢀdistillation of this product at atmospheric pressure using a cooled
receiver afforded 1.66 g of 6 (80%) as a colorless oil; bp 60°C/760 Torr. 1H NMR (CDCl3, 200 MHz) δ:
13
4.01 (2H, s, Hꢀ3), 3.31 (3H, s, MeO), 2.33 (1H, s, Hꢀ1); C NMR (50 MHz, CDCl3) δ: 79.2, 74.6, 59.5,
57.0; Anal. Calcd for C4H6O: C, 68.54; H, 8.63. Found: C, 68.51; H, 8.65.
3,3,3-Triethoxy-1-propyn (11): Compound 11 was prepared in twoꢀstep sequence shown below:
Trimethylsilyl acetylene (455 mg, 650 ꢁL, 4.63 mmol) was dissolved in 5 mL of dry Et2O under
argon atmosphere and a 3 M solution of ethyl magnesium bromide in Et2O (5.10 mmol, 1.7 mL). The
reaction mixture was stirred for 1 hr at room temperature, then raised to efflux for 15 min before cooling
back down to room temperature. Once cooled, a solution of 1.2 mL (1.07 g, 5.05 mmol) tetraethyl
orthocarbonate in 5 mL of Et2O was added dropwise. After the addition was complete, the reaction was
brought to gentle reflux and allowed to stir overnight. The reaction mixture was then poured into 10 mL
of saturated aqueous NH4Cl, and this was extracted four times with 5 mL of diethyl ether. Combined
ethereal solutions were dried over anhydr. Na2SO4 and the ether was removed on a rotatory evaporator
to give a yellowish liquid. Bulbꢀtoꢀbulb distillation yielded 750 mg (70 %) of trimethylsilyl triethyl
orthopropiolate as a colorless oil. Subsequently this compound was dissolved in 25 mL of methanol and
450 mg (3.24 mmol) of potassium carbonate was added at room temperature. After 1 hr, 30 mL of
pentane was added and reaction was stirred for additional 30 min, after separation of pentanique phase,
the methanolic one was extracted two times with pentane. Combined pentanique phases were washed
with water and dried over Na2SO4. The solvent was removed under diminished pressure (650 mbar,
bath 35 ºC) and the residue was filtrated rapidly through silica gel pad (eluent 10% of Et2O in pentane)
to afford 305 mg (55 %) of acetylene 8. 1H NMR (200 MHz, CDCl3) δ: 3.60 (6H, q, CH3CH2O), 2.31 (1H,
13
s, CH); 1.15 (9H, t, CH3CH2O); C NMR (50 MHz, CDCl3) δ: 108.5, 98.7, 89.1, 59.2, 15.1, 0.1; Anal.
Calcd for C9H13O3: C, 62.77; H, 9.36. Found: C, 62.74; H, 9.40.
S5

Synthesis of (R)-4-ethynyl-2,2-dimethyl-1,3-dioxane (12): Acetylene 12 was prepared following
sequence shown below:
Synthesis of A1:6 To (R)ꢀmalic acid (1.77 g, 13.2 mmol) was added trifluoroacetic anhydride
(7.5 mL), and the reaction mixture was stirred for 40 min. After removal of the remaining trifluoroacetic
anhydride under diminished pressure, MeOH (10 mL) was added to the remaining solid, which was
stirred for 1.5 h at room temperature. Volatile materials were removed under diminished pressure and
1
the residue was crystallized from ether/hexane to give 1.61 g (84%) of ester A1. H NMR (200 MHz,
CDCl3) δ: 4.30 (1H, dd, J 6.0, 4.2 Hz, Hꢀ2), 3.81 (3H, s, Me), 2.90 (1H, dd, J 16.5, 4.2 Hz, Hꢀ3a), 2.82
(1H, dd, J 16.5, 6.0 Hz, Hꢀ3b).
Synthesis of A3:7 A 1M solution of BH3ꢀMe2S (22 mmol, 22 mL) in THF was added dropwise to
a solution of acid A1 (1.61 g, 10.9 mmol) in 50 mL of dry THF at ꢀ15 °C under argon. The mixture was
allowed to warm to room temperature and stirred for 24 h. The excess of borane was carefully
destroyed by dropwise addition of 20 mL of MeOH and concentrated. The residue was coꢀevaporated
three times with MeOH. The residue was diluted with AcOEt and filtered through Celite pad. Organic
solution was concentrated under diminished pressure to give the diol A2, which was used in the next
1
step without further purification. H NMR (200 MHz, CDCl3) δ: 4.70 (1H, dd, J 6.7, 4.5 Hz, Hꢀ2), 4.00
(2H, t, J 5.6 Hz, Hꢀ4), 3.81 (s, 3H, Me), 2.25 (1H, m, Hꢀ3a), 2.06 (1H, m, Hꢀ3b).
Subsequently, the crude diol A2 (1.46 g, 10.9 mmol) was dissolved in 15 mL of dry DMF and 50
mL of 2,2ꢀdimethoxypropane, and PPTS (125 mg, 0.5 mmol) was added. The mixture was stirred for 24
h at room temperature and washed with saturated aqueous NaHCO3, extracted with CH2Cl2, dried over
MgSO4 and evaporated in diminished pressure. Chromatography on silicagel (hexane/AcOEt 75:25 +
5% Et3N) yielded, 1.14 g (60%) of A3 as a yellow oil: 1H NMR (200 MHz, CDCl3) δ: 4.52 (1H, m, Hꢀ2),
13
3.95 (2H, m, Hꢀ4), 3.75 (3H, s, Me), 2.03ꢀ1.73 (2H, m, Hꢀ3), 1.50 (6H, s, 2xMe); C NMR (50 MHz,
CDCl3) δ: 171.0, 98.7, 68.3, 59.1, 51.9, 29.2, 27.2, 19.7; IR (film) ν: 1730 cmꢀ1.
6 Solladie, G.; Arce, E.; Bauder, C.; Carreno, M.C. J. Org. Chem. 1998, 63, 2332ꢀ2337.
7 Hayashi, Y.; Yamaguchi, J.; Shoji, M. Tetrahedron 2002, 58, 9839ꢀ9846.
S6

Synthesis of (R)-4-ethynyl-2,2-dimethyl-1,3-dioxane (12): Ester A3 (0.94 g, 5.37 mmol) was
dissolved in 15 mL of freshly distilled CH2Cl2 and a solution was cooled to ꢀ78 ºC. Then a 1 M solution of
DIBALꢀH in heptane (6.5 mmol, 6.5 mL) was added dropwise. The progress of reduction was monitored
by TLC. After consumption of ester reaction was quenched by addition of 10 mL of anhydrous MeOH
and obtained suspension was warmed up to 0 ºC. Then 1.48 g (10.7 mmol) of anhydrous K2CO3 was
added in two portions, followed by addition of BestmannꢀOhira reagent (1.25 g, 6.5 mmol) and additional
amount of dry MeOH (20 mL). A cooling bath was removed and a suspension was stirred overnight. The
reaction was quenched with aqueous soln. of NH4Cl (30 mL), stirred for additional 30 min and extracted
with pentane. Separated organic phase was dried over anhydrous Na2SO4 followed by removal of
solvent under diminished pressure. Residue was purified by chromatography on silica gel (eluent: 10%
Et2O in pentane) to afford 0.6 g (80%) of acetylene 12 as a colorless oil. [α]D +16.8 (c 0.75, CH2Cl2 ) [lit.8
+16.4 (c 0.7, CHCl3)]; 1H NMR (200 MHz, CDCl3) δ: 4.69 (1H, m, Hꢀ3); 4.08ꢀ3.76 (2H, m, Hꢀ5a/b); 2.47
(1H, d, J 2.2 Hz, Hꢀ1), 2.16ꢀ1.88 (1H, m, Hꢀ4a), 1.80ꢀ1.64 (1H, m, Hꢀ4b), 1.46 and 1.44 (6H, 2xs, 2xMe);
13C NMR (50 MHz, CDCl3): δ: 99.4, 82.9, 73.2, 60.4, 59.5, 31.9, 30.3, 19.7; IR (film) ν: 2121, 1107 cmꢀ1;
HR MS (ESI): Calcd for C8H12O2Na [M+Na+]: 163.0735. Found: 163.0732; Anal. Calcd for C8H12O2: C,
68.54; H, 8.83. Found: C, 68.59; H, 8.65.
Synthesis of (2R,3R,5S)-5-ethynyl-2,3-dimethoxy-2,3-dimethyl-1,4-dioxane (13): Acetylene 13 was
prepared followed sequence as shown below:
Synthesis of A4:9 BF3ꢀEt2O (643 mg, 0.6 mL, 4.53 mmol) was added to to a stirred solution of
Dꢀmanitol (6.2 g, 33.8 mmol), trimethyl orthoformate (16 mL, 146 mmol) and butaneꢀ2,3ꢀdione (6 mL,
68.4 mmol) in MeOH (35 mL) at room temperature, under argon atmosphere. After 5 hrs, the reaction
mixture was neutralized by addition of Et3N (0.75 mL, 5.4 mmol) and the solvent was removed in vacuo.
8 Robles, O.; McDonald, F.E. Org. Lett. 2008, 10, 1811ꢀ1814.
9
(a) Hense, A.; Ley, S.V.; Osborn, H.M.I.; Owen, D.R.; Poisson, J.ꢀF.; Warriner, S.L.; Wesson, K.E. J. Chem. Soc., Perkin
Trans. 1 1997, 2023ꢀ2031; (b) Michel, P.; Ley, S.V. Synthesis 2003, 1598ꢀ1602
S7

The residue was dissolved in CH2Cl2 (150 mL) and washed with solution of NaCl (30 mL of water and
30 mL of brine). The organic phase was dried over anhydr. Na2SO4, filtered and concentrated in vacuo.
The crude product A4 was used in next without further purification. Analytical sample was obtained by
1
recrystalization with hexane to give diol A4 as a white solid. H NMR (500 MHz, CDCl3) δ: 4.07 (2H,
ddd, J 11.3, 6.5, 3.5 Hz), 3.71 (2H, t, J 11.3 Hz), 3.64 (2H, dd, J 11.3, 3.5 Hz), 3.26 (6H, s), 3.25 (6H, s),
2.78 (2H, d, J 6.5 Hz), 1.26 (6H, s), 1.25 (6H, s); 13C NMR (125 MHz, CDCl3) δ: 99.3, 98.1, 64.5, 68.3,
61.0, 48.1, 48.0, 17.9, 17.5; IR (film) v: 3455, 1115 cmꢀ1.
Synthesis of A5: The NaIO4 (10.1 g, 44.1 mmol) was added portionwise over 5 min to a stirred
emulsion of the crude diol A4 in CH2Cl2 (100 mL) and sat. aq NaHCO3 (120 mL).The resulting mixture
was stirred while the internal temperature is maintained below 35°C with water bath cooling. After the
mixture was stirred for overnight , 25 g of magnesium sulfate was added and stirring was continued for
20 min. The slurry was filtered. The filter cake was removed, transferred back into the flask, 200 mL of
dichloromethane was added, and the resulting slurry was stirred for 10 min. Again, the slurry was
vacuumꢀfiltered and the filtrate was combined with previous one. Subsequently, filtrate was stirred with
Na2S2O3 (5 g) for 30 min. Then the solution was filtered and concentrated in vacuo. The factional
distillation using a Vigreux column (bp 94ꢀ99º/1 Torr) gave aldehyde A5 as a colorless oil (5.6 g, 40%,
2 steps). 1H NMR (200 MHz, CDCl3) δ: 9.63 (1H, s, CHO), 4.32 (1H, dd, J 10.0, 5.0 Hz, Hꢀ2), 3.75ꢀ3.65
(2H, m, Hꢀ3a/b), 3.32 (3H, s, MeO), 3.25 (3H, s, MeO), 1.38 (3H, s, Me), 1.27 (3H, s, Me); 13C NMR (50
MHz, CDCl3) δ: 200.1, 99.8, 98.4, 72.2, 58.1, 48.3, 48.1, 17.55, 17.49.; IR (film) v: 1735, 1115 cmꢀ1.
Homologation of aldehyde A5. Synthesis of 13: An anhydrous K2CO3 (2.33 g, 16.8 mmol)
was added portionwise to a cooled solution of aldehyde A5 (1.60 g, 7.8 mmol) in dry MeOH (50 mL).
Next, BestmannꢀOhira reagent (2.42 g, 12.6 mmol) was added dropwise, and reaction mixture was
stirred overnight. Then reaction was quenched by treatment with sat. aqueous NH4Cl (50 mL), stirred for
additional 30 min and extracted with pentane. Separated organic phase was dried over anhydrous
Na2SO4 followed by removal of solvent under diminished pressure. Residue was purified by
chromatography on silica gel (eluent: 10% Et2O in pentane) to afford 1.33 g (85%) of acetylene 13 as a
colourless oil: [α]D ―151 (c 0.9, CH2Cl2) [lit.10 ―149 (c 0.23, CHCl3)]; 1H NMR (500 MHz, CDCl3) δ: 4.65
(1H, ddd, J 11.0, 3.5, 2.2 Hz, Hꢀ3), 3.83 (1H, t, J 11.3, 11.0 Hz, Hꢀ4a), 3.55 (1H, dd, J 11.3, 3.5 Hz, Hꢀ
4b), 3.32 (3H, s, MeO), 3.27 (3H, s, MeO), 2.46 (1H, d, J 2.2 Hz, Hꢀ1), 1.32 (3H, s, Me), 1.27 (3H, s,
Me); 13C NMR (125 MHz, CDCl3) δ: 99.8, 98.2, 79.3, 75.1, 62.7, 59.1, 48.9, 48.4, 18.2, 17.9; IR (film) ν:
2330, 1116 cmꢀ1; HR MS (ESI): Calcd for C10H16O4Na [M+Na+]: 223.0941. Found: 223.0945; Anal.
Calcd for C10H16O4: C, 59.98; H, 8.05. Found: C, 60.01 H, 8.03.
10 Leyva, A.; Blum, F. Hewitt, P.; Ley, S.V. Tetrahedron 2008, 64, 2348ꢀ2358.
S8