Org. Synth. 2000, 77, 98
DOI: 10.15227/orgsyn.077.0098
SYNTHESIS OF (S,E)-1-(METHOXYMETHOXY)-1-TRIBUTYLSTANNYL-2-BUTENE
[
Stannane, tributyl[1-(methoxymethoxy)-2-butenyl]-, [S-(E)]-
]
Submitted by James A. Marshall, Albert W. Garofalo, and Kevin W. Hinkle
1
.
Checked by Peter Belica and Steven Wolff.
1. Procedure
Caution! Many organotin compounds are highly toxic. All operations should be conducted in an efficient fume hood. Gloves and appropriate eye protection should be worn while performing these experiments.
A. A 500-mL, one-necked, round-bottomed flask is equipped with a Teflon-coated magnetic stirring bar
(Note 1), rubber septum and nitrogen inlet. The flask is charged with anhydrous tetrahydrofuran (THF) (150 mL) followed by
diisopropylamine (4.60 mL, 32.8 mmol). The solution is stirred at 0°C and BuLi is added (2.5 M solution in hexane, 12.2 mL, 30.4 mmol). After 15 min,
tributyltin hydride (7.70 mL, 27.8 mmol, (Note 2)) is added and the resulting yellow solution is stirred for 20 min. The solution is cooled to −78°C by means of a dry ice-acetone bath and
crotonaldehyde (2.10 mL, 25.3 mmol, (Note 2)) is added. After 30 min a solution of
1,1'-(azodicarbonyl)dipiperidine (ADD) (8.31 g, 32.9 mmol, (Note 2)) in THF (65 mL) is added by means of a cannula. The resulting dark red reaction mixture is warmed to 0°C and stirred for 1 hr (Note 3). The reaction is then quenched with
100 mL of aqueous saturated ammonium chloride
solution (Note 4) and extracted with two
100-mL portions of ether
. The aqueous phase is saturated with
sodium chloride
and extracted with
100 mL of ether
. The organic extracts are combined, dried over
magnesium sulfate
, filtered, and the solution is concentrated by rotary evaporation to a volume of 100 mL (Note 5). The orange solution is separated from a yellow precipitate by means of a cannula into a 2-L, two-necked, round-bottomed flask equipped with an overhead stirrer and containing
1 L of vigorously stirring hexane
(Note 2) under a nitrogen atmosphere (Note 6). The resulting mixture is filtered through a glass-fritted funnel and the solvent is removed by rotary evaporation to afford the crude acyl stannane as a clear orange oil. This oil is dissolved in
65 mL of THF and immediately subjected to reduction with
2,2'-dihydroxy-1,1'-binaphthyl-lithium aluminum hydride (BINAL-H) (Part B).
Because of the lability of the acyl stannane it is important to have a freshly prepared solution of BINAL-H at −78°C ready for addition of the acyl stannane. This is best achieved by starting the following reduction procedure just prior to the acyl stannane sequence.
B. A 500-mL, two-necked, round-bottomed flask is equipped with a Teflon-coated magnetic stirring bar
(Note 1), condenser, rubber septum and nitrogen inlet. The flask is charged with a suspension of
lithium aluminum hydride (LiAlH4) powder (2.13 g, 53.4 mmol) in 110 mL of anhydrous THF. The suspension is stirred at room temperature and a solution of
ethanol (EtOH) (3.13 mL, 53.4 mmol, (Note 7)) in
10 mL of THF is added dropwise over a period of 15 min with vigorous evolution of
hydrogen
gas. The mixture is stirred for 20 min and a solution of
(R)-1,1'-bi-2-naphthol (16.0 g, 55.8 mmol, (Note 8)) in
60 mL of THF is added over 1 hr by means of a cannula. The resulting cloudy, milky solution is refluxed for 2 hr (Note 9). The solution is cooled to −78°C in a dry ice-acetone bath and a solution of the acyl stannane in
65 mL of THF (Part A) is added over 45 min by means of a cannula. The reaction mixture is stirred for 16 hr (Note 10) as the bath slowly warms to room temperature. The reaction is quenched by the careful addition of
100 mL of aqueous saturated ammonium chloride
solution and diluted with 100 mL of water and
200 mL of ether
. The layers are separated and the aqueous layer is acidified by the addition of
200 mL of 1.0 M hydrochloric acid (HCl) and extracted with two
200-mL portions of ether
. The organic layers are combined and washed with
200 mL of aqueous saturated sodium bicarbonate
solution, dried over magnesium sulfate, filtered and the solvent is removed by rotary evaporation.
Hexane (100 mL) is added and distilled from the solution by rotary evaporation to ensure complete removal of residual ether and THF (Note 11). The solid yellow residue is triturated with
200 mL of hexane
and filtered. Solvent is removed from the filtrate by rotary evaporation and the yellow oil is again triturated with
200 mL of hexane
and filtered (Note 12). Solvent is again distilled from the filtrate by rotary evaporation to afford 8.97 g of crude hydroxy stannane as a yellow oil (Note 13).
While the α-hydroxy stannane is not as labile as the acyl stannane precursor, it should generally be converted to the ether derivative immediately after isolation.
C. The hydroxy stannane is dissolved in
100 mL of anhydrous methylene chloride
in a 250-mL, one-necked, round-bottomed flask equipped with a Teflon-coated magnetic stirring bar. The yellow solution is stirred at 0°C and
diisopropylethylamine (i-Pr2NEt) (8.80 mL, 50.5 mmol) is added, followed by
chloromethyl methyl ether (2.90 mL, 38.2 mmol). After 5 hr the reaction is quenched with
100 mL of aqueous saturated ammonium chloride
solution. The layers are separated and the aqueous layer is extracted with two
100-mL portions of ether
. The organic layers are combined, dried over magnesium sulfate, filtered, and the solvent is distilled by rotary evaporation. The residue is purified by column chromatography on silica gel
(Note 14). Elution with hexane followed by EtOAc-hexane (1:9) affords 4.1-5 g (40-49% yield) of
(S,E)-1-methoxymethyl)-1-tributylstannyl-2-butene
(Note 15).
2. Notes
1.
All apparatus was dried by alternately evacuating the flask while heating with a flame and venting in dry
nitrogen gas.
2.
Tributyltin hydride, 97%, crotonaldehyde, 99%, 1,1'-(azodicarbonyl)dipiperidine, 99%, and lithium aluminum hydride, 95%, were purchased from Aldrich Chemical Company, Inc.
Hexane refers to a distilled, isomeric mixture of C
6H
14.
3.
A viscous oil may form which makes stirring difficult. If this occurs, the flask is removed from the bath and shaken by hand until stirring can be resumed.
4.
The reaction is monitored by TLC (silica gel; 1:9 EtOAc-hexane). The TLC plate is developed by dipping into a 0.02 M solution of
phosphomolybdic acid in EtOH. The initially formed
hydroxy stannane (R
f = 0.52) will stain blue without heating. The acyl stannane (R
f = 0.69) is observed by charring the plate.
5.
Because of the air sensitive nature of the acyl
stannane, the flask is vented with
argon after removal of solvent.
6.
A large volume of
hexane is required to precipitate fully residual ADD and its reduction product. Alternatively the
ether extracts may be concentrated to dryness and triturated with
250 mL of hexane
.
7.
The
ethanol is distilled from
calcium hydride
and stored over molecular sieves.
8.
Incomplete reduction of the acyl stannane is observed when fewer equivalents of BINAL-H are employed.
9.
It was discovered by J. C. Saddler and co-workers at Upjohn that for reproducible results it was necessary to reflux the mixture of
binaphthol, LiAlH
4, and EtOH before performing the reduction. Enantioselective reduction of the acyl
stannane can also be effected with Chirald, albeit with slightly diminished enantioselectivity.
2
10.
The reduction is generally complete within a few hours and may be monitored by TLC
(Note 4). As stated in the procedure section, the submitters recommend that the hydroxy stannane not be stored after isolation. It can, however, be kept in the reaction mixture overnight.
11.
The ensuing trituration is most efficient when residual ether and THF are completely removed.
12.
Because of a slight solubility of the
binaphthol in the crude hydroxy stannane mixture, two triturations are required. The
binaphthol is recrystallized as previously described.
3 Generally >90% of purified
binaphthol is recovered.
13.
The checkers found that the residue after removal of solvent contained water, which they removed azeotropically with
toluene. Subsequent incomplete removal of the
toluene led to amounts of stannane greater than theoretical.
14.
The crude product was chromatographed on a
silica gel column (ca. 150 g) using
300 mL of hexane
followed by EtOAc-hexane (1:9 v/v) until complete elution. Because of a slight impurity, the early and late fractions of this separation were yellow; the middle fractions were colorless.
15.
The following physical data were recorded:
[α]
D
25 −62.6 (CH
2Cl
2,
c 2.3),
1H NMR (400 MHz, CDCl
3) δ: 0.90 (m, 15 H), 1.31 (m, 6 H), 1.50 (m, 6 H), 1.68 (d, 3 H, J = 6.2), 3.33 (s, 3 H), 4.56 (m, 1 H), 4.49, 4.67 (ABq, 2 H, J = 6.6), 5.39 (dq, 1 H, J = 15.4, 6.2), 5.58 (dd, 1 H, J = 15.4, 7.7)
;
13C NMR (75 MHz, CDCl
3) δ: 8.9, 13.5, 17.5, 27.3, 29.0, 55.2, 72.4, 95.0, 119.9, 132.5
. Anal. Calcd for C
18H
38O
2Sn: C, 53.35; H, 9.45. Found: C, 53.63; H, 9.28. The rotation corresponds to an enantiomeric excess of greater than 90% as previously reported.
2
Handling and Disposal of Hazardous Chemicals
The procedures in this article are intended for use only by persons with prior training in experimental organic chemistry. All hazardous materials should be handled using the standard procedures for work with chemicals described in references such as "Prudent Practices in the Laboratory" (The National Academies Press, Washington, D.C., 2011 www.nap.edu). All chemical waste should be disposed of in accordance with local regulations. For general guidelines for the management of chemical waste, see Chapter 8 of Prudent Practices.
These procedures must be conducted at one's own risk. Organic Syntheses, Inc., its Editors, and its Board of Directors do not warrant or guarantee the safety of individuals using these procedures and hereby disclaim any liability for any injuries or damages claimed to have resulted from or related in any way to the procedures herein.
3. Discussion
Chiral α-alkoxyallylic stannanes [O-MOM, O-BOM (benzyloxymethyl)], as well as their α-siloxy (O-TBS) analogues, are useful reagents for chain homologation (
Figure 1). The title compound has been used for the synthesis of carbohydrate homologues, cembranes, and macrolide precursors.
4
5,6
7 The reagents are readily prepared and can be stored for extended periods with no apparent decomposition or racemization. The preparation of chiral α-siloxy allylic stannanes parallels the above procedure with the substitution of appropriate silylating agents in Part C. These stannanes undergo highly selective Lewis-acid promoted additions to aldehydes to give syn S
E' addition products.
2
Figure 1
These reagents are also useful for the preparation of 1,2-diols. Upon exposure to Lewis acids such as
boron trifluoride etherate (BF3·OEt2), the α-alkoxy and α-siloxyallyl stannanes undergo a stereospecific, intermolecular 1,3-isomerization to give γ-alkoxy- and γ-siloxy allylic stannanes.
3,8,9 When
tert-butyldimethylsilyl trifluoromethanesulfonate
is substituted for
chloromethyl methyl ether in the above procedure, the isomeric γ-siloxy allylic stannane can be obtained directly with no loss of enantioselectivity.
8 These stannanes can then be added to various aldehydes to give monoprotected 1,2-diols with high diastereoselectivity.
10
Appendix
Chemical Abstracts Nomenclature (Collective Index Number);
(Registry Number)
(S,E)-1-(Methoxymethoxy)-1-tributylstannyl-2-butene:
Stannane, tributyl[1-(methoxymethoxy)-2-butenyl]-, [S-(E)]- (12); (131433-64-2)
Diisopropylamine (8);
2-Propanamine, N-(1-methylethyl)- (9); (108-18-9)
Butyllithium:
Lithium, butyl- (8,9); (109-72-8)
Tributyltin hydride:
Stannane, tributyl- (8,9); (688-73-3)
Crotonaldehyde:
Crotonaldehyde, (E)- (8);
2-Butenal, (E)- (9); (123-73-9)
1,1'-(Azodicarbonyl)dipiperidine [ADD]:
Diimide, bis(piperidinocarbonyl)- (8);
Piperidine, 1,1'-(azodicarbonyl)bis- (9); (10465-81-3)
Lithium aluminum hydride:
Aluminate(1−), tetrahydro-, lithium (8);
Aluminate(1−), tetrahydro-, lithium, (T-4)- (9); (16853-85-3)
(R)-(+)-1,1'-Bi-2-naphthol:
[1,1'-Binaphthalene]-2,2'-diol, (R)-(+)- (8);
[1,1'-Binaphthalene]-2,2'-diol, (R)- (9); (18531-94-7)
Phosphomolybdic acid:
Molybdophosphoric acid (H3PMo12O40), hydrate (9); (51429-74-4)
Chloromethyl methyl ether
CANCER SUSPECT AGENT:
Ether, chloromethyl methyl (8);
Methane, chloromethoxy- (9); (107-30-2)
Chirald:
Benzenethanol, α-[2-(dimethylamino)-1-methylethyl]-α-phenyl-, [S-(R,R)]- (9); (38345-66-3)
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