Checked by Darius J. Robinson and Amos B. Smith, III.
1. Procedure
A.
(Tributylstannyl)methanol. A
500-mL, three-necked, round-bottomed flask is equipped with a
magnetic stirring bar, a
rubber septum, an
argon inlet adapter, and a
150-mL, pressure-equalizing, dropping funnel fitted with a
rubber septum (Note
1). The flask is charged with
13.7 mL (0.098 mol) of diisopropylamine (Note
2) and
120 mL of dry tetrahydrofuran (Note
3), and then cooled with an
ice-water bath while
58.4 mL (0.093 mol) of a 1.60 M solution of butyllithium in
hexane (Note
4) is added dropwise via syringe over 15 min. After 30 min, a solution of
24.75 g (0.0850 mol) of tributyltin hydride (Note
5) in
50 mL of tetrahydrofuran is added dropwise via the
addition funnel over 50 min. After 30 min,
3.57 g (0.119 mol) of paraformaldehdye (Note
6) is added in one portion, the
ice bath is removed, and the heterogeneous yellow reaction mixture is stirred for 3 hr at room temperature. The resulting clear, colorless solution is diluted with
500 mL of petroleum ether and washed with 300 mL of water. The aqueous phase is separated and extracted with
150 mL of petroleum ether, and the combined organic layers are washed with
200 mL of saturated sodium chloride solution, dried over anhydrous
sodium sulfate, filtered, and concentrated at reduced pressure using a
rotary evaporator to afford approximately
30 g of
(tributylstannyl)methanol as a colorless oil, which was used in the next step without further purification (Note
7).
B.
Tributyl[(methoxymethoxy)methyl]stannane. A
1-L, three-necked, round-bottomed flask is equipped with a
mechanical stirrer, an argon inlet adapter, and a rubber septum (Note
1). The flask is charged with the
(tributylstannyl)methanol prepared in the previous reaction,
190 mL of dichloromethane (Note
8),
280 mL (3.16 mol) of dimethoxymethane (Note
9), and 50 g of powdered 4 Å molecular sieves (Note
10).
Boron trifluoride etherate (13.0 mL, 0.106 mol) (Note
11) is added dropwise over 2 min via syringe to the vigorously stirred reaction mixture, and the resulting orange suspension is stirred at room temperature for 13 hr, and then filtered through a
2-cm pad of Celite in a
sintered-glass funnel. The filter cake is washed with
250 mL of dichloromethane, and the combined filtrates are washed with two
250-mL portions of saturated sodium bicarbonate solution. The combined aqueous layers are extracted with
250 mL of dichloromethane, and the combined organic phases are then washed with
250 mL of saturated sodium chloride solution, dried over anhydrous
sodium sulfate, filtered, and concentrated at reduced pressure using a rotary evaporator. The residual pale yellow oil (
30 g) is dissolved in
20 mL of hexane and applied to
150 g of alumina (Note
12) packed in a
4.5-cm diameter column. The column is eluted with
1.3 L of 1% ethyl acetate-hexane (Note
13). The total eluant is concentrated at reduced pressure using a rotary evaporator, and the residual colorless oil is transferred to a
100-mL, round-bottomed flask and distilled through a
10-cm Vigreux column to furnish
23 g (
74% overall yield based on
tributyltin hydride) of
tributyl[(methoxymethoxy)methyl]stannane as a colorless liquid, bp
117°C (0.34 mm) ((Note
14) and (Note
15)).
2. Notes
1. The glass components of the apparatus are immersed in a solution of
19.8 g of potassium hydroxide in 20 mL of water and
88 mL of ethanol for 20 min, dried overnight in a 150°C oven, and then assembled and maintained under an atmosphere of
argon during the course of the reaction. This procedure removes traces of materials that otherwise can catalyze decomposition of the organotin reagents employed in the reaction.
3.
Tetrahydrofuran was distilled from
sodium benzophenone ketyl immediately before use.
4.
Butyllithium was purchased from Aldrich Chemical Company, Inc. and titrated using the method of Watson and Eastham.
3
5.
Tributyltin hydride was freshly prepared by the method of Hayashi et al.
4 Commercial
tributyltin hydride (Aldrich Chemical Company, Inc.) can also be used, but in this case the yield of product is 5–7% lower.
7. If desired, the product can be purified by column chromatograpy on 230–400 mesh silica gel (50 times by weight, elution with 5–10%
ethyl acetate-hexane).
(Tributylstannyl)methanol exhibits the following spectral properties: IR (film) cm
−1: 3320, 2970, 2940, 2880, 2860, 1465, 1440, 1380, 1360, 1345, 1295, 1255, 1185, 1155, 1075, 1045, 1025, 985, 875;
1H NMR (300 MHz, CDCl
3) δ: 0.8–1.1 (m, 15 H), 1.2–1.7 (m, 13 H), 4.02 (d, 2 H, J = 4.5).
10. Linde type 4 Å molecular sieve pellets were crushed using a mortar and pestle and then dried under vacuum (0.3 mm) at 300°C
5 for 15 hr prior to use.
12. EM Science 80-325 mesh alumina was used for this filtration.
13. Filtration of the crude product through alumina prior to distillation is necessary to obtain pure material. If the filtration step is omitted, product of only 85–90% purity is obtained.
14. The purity of this material was determined to be >99% by gas chromatographic analysis (
0.25 mm × 30 m DB-1701 fused silica capillary column, 12 psi column pressure, 120°C for 2 min, 120–250°C at 10°C/min, then 250°C; retention time 13.1 min).
15. The product has the following spectral properties: IR (film) cm
−1: 2970, 2930, 2880, 2770, 1465, 1420, 1395, 1380, 1345, 1295, 1245, 1205, 1150, 1100, 1040, 965, 930, 875, 730;
1H NMR (250 MHz, CDCl
3) δ: 0.8–1.1 (m, 15 H), 1.2–1.7 (m, 12 H), 3.33 (s, 3 H), 3.74 (s, 2 H), 4.52 (s, 2 H);
13C NMR (75 MHz, CDCl
3) δ: 8.9, 13.6, 27.3, 29.1, 54.9, 57.6, 99.4. Anal. Calcd for C
15H
34O
2Sn: C, 49.34; H, 9.39. Found: C, 49.68, H, 9.56.
All toxic materials were disposed of in accordance with "Prudent Practices in the Laboratory"; National Academy Press; Washington, DC, 1995.
3. Discussion
Hydroxymethyl anion equivalents play an important role as building blocks in the synthesis of complex organic compounds.
6 Still
7 has previously demonstrated the utility of Bu
3SnCH
2OCH(OEt)CH
3 as a hydroxymethyl anion equivalent. The preparation of this reagent involves the addition of
tributylstannyllithium to
paraformaldehyde followed by the protection of the resultant alcohol with
α-chloroethyl ethyl ether. Transmetalation of the organostannane with one equivalent of
butyllithium then furnishes an α-alkoxymethyllithium reagent which adds to carbonyl compounds in good yield. Hydrolysis of the ethoxyethyl protective group provides the desired primary alcohols.
Like Still's reagent,
tributyl[(methoxymethoxy)methyl]stannane incorporates an alcohol protective group that can be conveniently unmasked under mild acidic conditions. However, an advantageous feature of this MOM ether derivative is that, in contrast to Still's reagent, it is achiral. In many applications the introduction of an additional chiral center into synthetic intermediates is undesirable because of the complications associated with the manipulation, analysis, and purification of diastereomeric mixtures.
Methoxymethylation of alcohols is generally achieved through alkylation with
chloromethyl methyl ether. The procedure described here for the preparation of Bu
3SnCH
2OCH
2OCH
3 avoids the use of the highly toxic
chloromethyl ether by employing an acid-catalyzed acetal exchange reaction with
dimethoxymethane for the key protection step. Two related procedures have been developed for the methoxymethylation of
(tributylstannyl)methanol based on this strategy.
8,9,10 The protocol described here employs BF
3-etherate and molecular sieves
8,11 to promote the acetal exchange and results in a higher yield of product compared to the alternative Fujita procedure
12 that uses
phosphorus pentoxide. In this fashion the title compound is obtained in excellent purity in 74% overall yield from
tributyltin hydride. An application of this organotin compound which illustrates its use as a hydroxymethyl anion equivalent may be found on
p. 493.
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