Bowling et al.
JOCArticle
a pale yellow oil. 1H NMR (CDCl3) δ 4.51 (q, J = 6.6 Hz, 1H),
2.91 (s, 1H), 1.43 (d, J = 6.6 Hz, 3H). 13C NMR (CDCl3) δ 82.1,
59.3, 44.5, 24.167. EIMS (70 eV) m/z Mþ 149 (11), 133 (100), 121
(6), 105 (11), 84 (8), 69 (32).
Hepta-2,5-diyn-4-one (15d). Method 1. A mixture of 20 mL of
dry CH2Cl2 and BaMnO4 (1.67 g, 6.50 mmol) was prepared and
added to the 100 mL round-bottom flask containing alcohol
14d (0.16 g, 1.46 mmol). After stirring under nitrogen at room
temperature for 45 min, the reaction was complete by TLC. The
contents of the flask were flash-filtered through a short Celite
plug. The filtrate was dried with MgSO4, filtered, concentrated
under reduced pressure, and purified with flash column chro-
matography (CHCl3). Concentration of the appropriate frac-
tions revealed ketone 15d (0.148 g, 1.39 mmol, 95%) as a peach-
Hepta-3,5-diyn-2-ol (10d). CuCl (13.4 mg, 0.136 mmol) and
30% n-BuNH2/H2O (6.0 mL, 14.9 mmol) were added to a 25 mL
round-bottom flask and the mixture was stirred under nitro-
gen. The cerulean blue solution was cooled to 0 °C. Propyne
(18b) (excess) was condensed into a 10 mL round-bottom
flask at -78 °C and cannula-transferred into the 25 mL round-
bottomed flask until there was a visible change in volume in the
25 mL round-bottom flask. The solution turned teal in color.
4-Bromobut-3-yn-2-ol (19b) (0.475 g, 3.2 mmol) was added
dropwise via syringe, and a fine yellow solid precipitated. The
mixture was warmed to room temperature and NH2OH/HCl
was added until the solution remained a golden color and the
precipitate dissolved. The mixture was poured into a separa-
tory funnel containing water and ether. The aqueous layer
was extracted three times with ether. The combined organic
layers were dried with MgSO4, filtered, concentrated under
reduced pressure, and purified with flash column chromatography
(CHCl3). Concentration of the appropriate fractions revealed
alcohol 10d (0.202 g, 1.87 mmol, 59% yield) as a very pale yellow
oil. 1H NMR (CDCl3) δ 4.50 (q, J = 6.6 Hz, 1H), 2.86 (s, br, 1H),
1.89 (s, 3H), 1.41 (d, J = 6.6 Hz, 3H). 13C NMR (CDCl3) δ 77.5,
76.9, 69.2, 63.9, 58.7, 24.2, 4.4.
1
colored powder. H NMR (CDCl3) δ 2.06 (s, 6H). 13C NMR
(CDCl3) δ 161.3, 90.7, 81.5, 4.3. EIMS (70 eV), m/z Mþ 106 (28),
91 (11), 84 (17), 78 (42), 67 (28), 58 (100).
Method 2. A mixture of 10 mL of dry CH2Cl2, 1.29 g (5.98
mmol) of pyridinium chlorochromate (PCC), and a small
amount of Celite was prepared in a round-bottom flask. A
solution of alcohol 14b in 10 mL of dry CH2Cl2 was transferred
to this flask. After stirring at room temperature for 2 h, the
reaction was complete by TLC. The contents of the flask was
filtered, with suction, through a plug of Celite. The filtrate was
concentrated under reduced pressure then purified via flash
chromatography (CH2Cl2). Concentration of the appropriate
fractions afforded 0.210 g (1.98 mmol, 78% yield) of ketone 15d
as a white powder. 1H NMR (CDCl3) δ 2.06 (s, 9H). 13C NMR
(CDCl3) δ 161.3, 90.7, 81.5, 4.3.
Hepta-2,5-diyn-4-one Tosylhydrazone (16d). Glacial acetic
acid (5.0 mL) and tosylhydrazide (0.413 g, 2.22 mmol) were
added to a 100 mL round-bottom flask containing 0.237 g
(2.24 mmol) of ketone 15d. The mixture was stirred overnight
under nitrogen, then poured into a separatory funnel containing
2:1 cold water and cold CH2Cl2. The organic phase was dried
with MgSO4, filtered, concentrated under reduced pressure, and
purified with flash chromatography (CHCl3). Concentration of
the appropriate fractions revealed 0.330 g (1.20 mmol, 54%
yield) of a 3:1 ratio of tosylhydrazone 16d to pyrazole P2d as a
white powder. Tosylhydrazone (16d): 1H NMR (CDCl3) δ 8.81
(s, br, 1H), 7.80 (d, J = 8.2 Hz, 2H), 7.28 (d, J = 8.2 Hz, 2H),
2.38 (s, 3H), 2.04 (s, 3H), 1.91 (s, 3H). 13C NMR (CDCl3) δ
144.5, 135.4, 129.8, 120.6, 101.0, 88.5, 75.4, 70.2, 4.8. HRMS
(ESI) calcd for C14H14N2O2SNaþ 297.0674, found 297.0681.
Pyrazole P2d: 1H NMR (CDCl3) δ 7.83 (d, J = 8.2 Hz, 2H), 7.26
(d, J = 8.2 Hz, 2H), 6.03 (s, br, 1H), 2.48 (s, 3H), 2.37 (s, 3H),
1.96 (s, 3H). 13C NMR (CDCl3) δ 145.8, 143.7, 139.5, 134.8,
130.1, 127.9, 112.7, 89.6, 71.6, 21.7, 13.1, 4.4. HRMS (ESI) calcd
for C14H14N2O2SNaþ 297.0674, found 297.0668.
Hepta-2,5-diyn-4-one Trisylhydrazone (20d). Method 1. Glacial
acetic acid (5 mL) and trisylhydrazide (0.37 g, 1.25 mmol) were
added to a 100 mL round-bottom flask containing 0.13 g (1.25
mmol) of ketone 15d. The mixture was allowed to stir overnight
under nitrogen, then poured into a separatory funnel containing
2:1 cold water and cold CH2Cl2. The organic phase was dried with
MgSO4, filtered, concentrated under reduced pressure, and pur-
ified with flash chromatography (CHCl3). Concentration of the
appropriate fractions revealed 0.19 g (0.49 mmol, 39% yield) of
trisylhydrazone 20d as a white powder. 1H NMR (CDCl3) δ 8.71
(s, br, 1H), 7.13 (s, 2H), 4.16 (septet, J = 6.6 Hz, 2H), 2.87 (septet,
J = 6.9 Hz, 1H), 2.07 (s, 3H), 1.90 (s, 3H), 1.24 (d, J = 6.6 Hz, 12
H), 1.21 (d, J = 6.9 Hz, 6H). 13C NMR (CDCl3) δ 153.7, 151.4,
131.5, 124.1, 119.7, 100.4, 88.2, 75.5, 70.3, 34.3, 30.2, 24.9, 23.7,
4.8, 4.4. HRMS (ESI) calcd for C22H30N2O2SHþ 387.2101, found
387.2083.
anti-Hepta-3,5-diyn-2-one Tosylhydrazone (12d). Dry CH2Cl2
(25 mL) and Dess-Martin periodinane (2.7146 g, 6.40 mmol)
were added to alcohol 10d (0.4752 g, 3.1895 mmol) and allowed
to stir under nitrogen at room temperature. The reaction was
shown to be complete by TLC after 1 h. Diethyl ether was added
and the resulting suspension was flash-filtered through a short
Celite plug into a round-bottom flask containing p-toluenesul-
fonhydrazide (0.615 g, 3.30 mmol). The mixture was allowed to
stir under nitrogen at room temperature overnight. The mixture
was filtered to remove insoluble hypervalent iodine species, and
the filtrate was washed with saturated sodium bicarbonate
solution. The organic layer was washed with saturated ammo-
nium chloride solution, and the combined aqueous layers were
extracted with diethyl ether. The combined organic layers were
dried with MgSO4, filtered, concentrated under reduced pres-
sure, and purified with flash column chromatography (CHCl3).
Concentration of the appropriate fractions revealed tosyl-
hydrazone 12d (0.291 g, 1.06 mmol, 33% yield) as a white
powder. 1H NMR (CDCl3) δ 8.36 (s, br, 1H), 7.80 (d, J = 8.4
Hz, 2H), 7.29 (d, J = 8.4 Hz, 2H), 2.40 (s, 3H), 2.03 (s, 3H), 2.01
(s, 3H). 13C NMR (CDCl3) δ 144.4, 135.6, 133.9, 129.8, 128.0,
88.0, 87.3, 63.6, 62.9, 22.5, 21.7, 4.9. HRMS (ESI) calcd for
[MHþ] 275.0854, found 275.0861.
Hepta-2,5-diyn-4-ol (14d). A flame-dried 100 mL round-
bottomed flask was charged with 30 mL of dry THF and the
mixture was cooled to -78 °C. n-BuLi (6.0 mL, 9.0 mmol, 1.5 M
solution in hexane) was added via syringe. Propyne (18b) was
condensed into the flask in excess (until there was a visible
change in volume in the flask). After the addition of methyl
formate (0.185 mL, 3.0 mmol), the mixture was stirred at -78 °C
for 1 h. The mixture was allowed to warm to -40 °C and was
maintained there for 45 min. Water was added and the reaction
mixture was warmed to room temperature. The mixture was
rinsed into a separatory funnel with H2O and ether. The aqu-
eous phase was extracted with ether (3 ꢀ 30 mL). The combined
organic extracts were dried with MgSO4, filtered, and concen-
trated under reduced pressure. The residue was purified via flash
chromatography (10% CH3CN/CH2Cl2) to reveal 315 mg (2.91
mmol, 97% yield) of alcohol 14d as a white powder. 1H NMR
(CDCl3) δ 5.07 (doublet of septets, J = 7.2 Hz, 2.4 Hz, 1H), 2.10
(d, J = 7.2 Hz, 1H), 1.89 (d, J = 2.4 Hz, 6H). 13C NMR (CDCl3)
δ 80.8, 77.2, 52.4, 3.7.
Method 2. A flask was charged with 220 mg (2.11 mmol) of
ketone 15d and 631 mg (2.11 mmol) of trisylhydrazide. Ethanol
was added dropwise with stirring until it formed a thick slurry.
This mixture was stirred for 18 h at room temperature (turning
into an orange homogeneous mixture). Some crystals precipi-
tated overnight. Crystallization was further induced with cooling
to 0 °C. Suction filtration afforded a yellow solid. Upon rinsing
J. Org. Chem. Vol. 75, No. 19, 2010 6389