Checked by Georg W. Schröder and K. Barry Sharpless.
1. Procedure
A.
(R)-(−)-Methyl 1,1'-binaphthyl-2,2'-diylphosphate. A
200-mL, three-necked flask equipped with a
magnetic stirrer and a
gas bubbler is charged with
20.0 g (57.4 mmol) of (R)-(−)-1,1'-binaphthyl-2,2'-diyl hydrogen phosphate (Note
1),
40 mL of N,N-dimethylacetamide, and
10.0 mL (105.7 mmol) of dimethyl sulfate (Note
2). The resulting pale-yellow oil is then treated cautiously in small portions with
10.4 g (123.8 mmol) of sodium bicarbonate. The addition causes gas evolution and foaming. Foaming subsides after ca. 20 min, and the resulting turbid yellow solution is stirred overnight at room temperature (Note
3).
The reaction mixture is poured into a mixture of
300 mL of toluene and
100 mL of ethyl acetate. The resulting milky solution is washed twice with 100-mL portions of deionized water and twice with
100-mL portions of brine and then dried over anhydrous
sodium sulfate. The drying agent is removed by filtration and the filtrate is concentrated on a
rotary evaporator under reduced pressure in a 50°C bath. The semisolid residue is slurried in
55 mL of ether and then collected by filtration on a
sintered-glass funnel. After the solid is washed 4 times with
10 mL of ether, it is set aside and the filtrate is evaporated to dryness. The residue is slurried in
10 mL of ether. The solid is collected on a glass frit and washed twice with
10 mL of ether. Both solids are combined and dried under reduced pressure to give
16.4 g (
45.2 mmol) (
79%) of
phosphate as an off-white powder, mp
215–217°C;
[α]D25 −526.8° (THF, c 1.16) (Note
4).
B. Crude (R)-(+)-1,1'-binaphthalene-2,2'-diol.
[Caution! Gases evolved in this step create a stench and are toxic. The use of an efficient fume hood is imperative (Note 5).]
A
2-L, three-necked flask equipped with
Y-tube, magnetic stirrer, dropping funnel topped with gas bubbler, thermometer, and
drying tube is charged with
14.7 g (40.6 mmol) of crude (R)-(−)-methyl 1,1'-binaphthyl-2,2'-diyl phosphate and
350 mL of dry toluene. The mixture is stirred under
nitrogen and heated with a
steam bath until dissolution occurs (44°C). The solution is then cooled in an
ice–water bath to 10°C. The
cooling bath is removed and a solution of
27.0 mL (91.8 mmol) of Red-Al (Note
6) in
35 mL of toluene is added from the
dropping funnel over a 90-min period. The mixture turns yellow, evolves a gas, and heats up to 26°C. Gas evolution ceases 20 min after the addition is completed. TLC analysis (
silica gel plate developed with
ethyl acetate) indicates that the reaction is complete.
The entire reaction mixture is poured into
430 mL of 10% hydrochloric acid (mild exothermic reaction). The organic layer is separated and washed with another
430-mL portion of 10% hydrochloric acid. After further washes with
150 mL of brine and 160 mL of deionized water, all aqueous layers are combined and back-extracted with a
550-mL portion of 3 : 2 toluene : methanol and two
300-mL portions of toluene. The combined organic layers are dried over anhydrous
sodium sulfate, and filtered. The solvent is removed on a rotary evaporator under reduced pressure in a 45°C bath to give
11.4 g (
98%) of crude product as a bright-yellow microcrystalline solid, mp
203–205°C.
C.
Recrystallization of (R)-(+)-1,1'-binaphthalene-2,2'-diol. A
200-mL flask with a
reflux condenser is charged with
11.4 g of crude (R)-(+)-1,1'-binaphthalene-2,2'-diol and
1.5 g of Norit A, and refluxed for 5 min. The hot solution is filtered through a pad of 5 g of Celite on a glass frit. The Celite and Norit A from the frit are slurried together with
1.5 g of Norit A in
70 mL of toluene, refluxed for 5 min, and filtered hot through a pad of 5 g of Celite on a glass frit. The Celite is washed with
70 mL of hot toluene. The combined filtrates are warmed to 50°C to dissolve the precipitated crystals and filtered once again while warm through a pad of 5 g of Celite on a glass frit, which is then washed with
40 mL of hot toluene. The filtrate is freed from solvent on a rotary evaporator and the residue is recrystallized from
75 mL of toluene with stirring. The mixture is stirred overnight at ambient temperature. The resulting suspension is filtered and the filter cake is washed with two
10-mL portions of toluene. The recrystallized product is then dried under reduced pressure (high vacuum) to give
9.62 g of white, microcrystalline material in the first crop. This material melts at
207–209°C,
[α]D25 +33.6° (THF, c 1.11) (Note
7) and (Note
8).
Concentration of the filtrate and
toluene washings under reduced pressure to ca. 11 mL affords, after cooling, collecting, washing 3 times with
3 mL of toluene, and drying the solid material, a second crop of product that weighs 1.04 g. This crop is an off-white microcrystalline powder, mp
204–206°C and
[α]D25 + 33.6° (THF, c 1.12) (Note
9).
The two crops (10.66 g) represent 94% recovery on recrystallization. The yield of recrystallized product is 92% in the reductive cleavage of the phosphate ester and 73% overall.
2. Notes
2.
Dimethyl sulfate was obtained from Aldrich Chemical Company, Inc. It is highly toxic and carcinogenic, and it should be handled only in a
well-ventilated hood.
3. The reaction was complete by TLC (silica gel plate) analysis. The consumption of starting material and the formation of product can be monitored using a 5 : 2 (v : v) mixture of
ethyl acetate :
hexane as the solvent.
4. The enantiomeric excess of this product was determined to be >99.5% using a chiral stationary phase HPLC (preparative Regis Pirkle Type 1-A, 10 × 250 mm id., 7.5 mL/min flow rate, 100-psi pressure,
10% 2-propanol in
hexane, detector at 284 nm). The
R-(−)-enantiomer is eluted first and the peaks are well separated.
2 Another batch of phosphate (
[α]D25 −507.7°C, THF, c 1.17) was shown to have 96.5% ee using the same conditions. The same reaction was also checked on a slightly smaller scale, using
18.8 g (
54.0 mmol) of
(R)-(−)-1,1'-binaphthyl-2,2'-diyl phosphate. The yield was
81%. The submitters report a yield of
80% for the reaction run on a 1.6-mol scale.
5. The
phosphorus hydride that evolves is highly toxic and creates a stench. Therefore, the checkers recommend that this reaction as well as the workup be performed in an efficient fume hood. The checkers found it advantageous to scrub the
phosphorus hydride that formed in a trap (shown below) by bubbling the evolving gases through a solution of
250 mL of bleach (5% sodium hypochlorite in water). During the reaction a constant flow of
nitrogen was applied to avoid contamination of the reaction flask with wet gases from the traps.

7. The enantiomeric excess of this product was determined to be >99.5% using the same conditions as mentioned in (Note
4). The peaks are well separated and the
R-(+)-enantiomer is eluted second.
2 Another batch obtained from reduction of phosphate having 96.5% ee had mp
207–209°C and
[α]D25 +33.5° (THF, c 1.12). This material had an enantiomeric excess of >99.5%, determined under the same conditions as described in (Note
4). The submitters report
[α]D25 +24.7° (THF, c 1.035) for material with mp
207–209°C [lit.
3 mp
206.5–207.5°C,
[α]D25 +34.3° (THF, c 1.1)].
8. The product has the following spectral properties:
1H NMR (1 : 1 CDCl
3 :
d6-DMSO) δ: 7.04 (d, 2H,
J = 8.8), 7.20–7.35 (m, 4 H), 7.40 (d, 2H,
J = 8.8), 7.92 (d, 2 H,
J = 8.8), 9.21 (s, 2 H).
9. The enantiomeric excess of this product was determined to be >99.5% using the same conditions as mentioned in (Note
4). The second crop obtained from the reduction of phosphate having 96.5% ee had mp
200–204°C and
[α]D25 +20.7° (THF, c 1.13). This (second crop) material had an enantiomeric excess of 86.5%, determined under the same conditions as described in (Note
4). The submitters report
[α]D25 +33.5° (THF, c 0.775) for material with mp
204–206°C.
3. Discussion
Appendix
Compounds Referenced (Chemical Abstracts Registry Number)
silica gel
brine
(R)-(+)-1,1'-BINAPHTHALENE-2,2'-DIOL
(R)-(−)-Methyl 1,1'-binaphthyl-2,2'-diylphosphate
(R)-(−)-1,1'-binaphthyl-2,2'-diyl hydrogen phosphate
Crude (R)-(+)-1,1'-binaphthalene-2,2'-diol
(R)-(−)-methyl 1,1'-binaphthyl-2,2'-diyl phosphate
Red-Al
(R)-(−)-1,1'-binaphthyl-2,2'-diyl phosphate
1,1'-Binaphthalene]-2,2'-diol,(R)-
hydrochloric acid (7647-01-0)
ethyl acetate (141-78-6)
methanol (67-56-1)
ether (60-29-7)
sodium bicarbonate (144-55-8)
sodium sulfate (7757-82-6)
nitrogen (7727-37-9)
dimethyl sulfate (77-78-1)
Norit A (7782-42-5)
toluene,
M toluene (108-88-3)
2-propanol (67-63-0)
sodium hypochlorite (7681-52-9)
Diazomethane (334-88-3)
lithium aluminum hydride (16853-85-3)
hexane (110-54-3)
phosphate
N,N-dimethylacetamide (127-19-5)
sodium bis(2-methoxyethoxy)aluminum hydride
phosphorus hydride (7723-14-0)
1,1'-binaphthyl-2,2'-diyl hydrogen phosphate (39648-67-4)
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