Organic Syntheses, Vol. 79, p. 59
Checked by Edward B. Holson and William R. Roush.
1. Procedure
2. Notes
1. The commercial mixture of xylenes was used as received without
further purification. Degassing was accomplished by bubbling
argon
through the solvent for 30 min.
2.
Indium powder,
−100 mesh, 99.99%, was purchased from Aldrich Chemical
Company, Inc.
3. Vigorous stirring is very important. Use of a large stir bar for
this reaction is crucial. During the course of the reaction the powdered
indium metal may adhere to the sides
of the flask. On occasion it was necessary to dislodge this powder from the walls
of the flask. The flask was removed from the heat source, allowed to cool below reflux,
and the walls of the flask were scraped with a
metal spatula.
Caution should be exercised when performing this operation to avoid burns
and the flask should be blanketed with argon to prevent solvent
flash. On a larger scale the submitters recommend use of a
mechanical
stirrer.
4. A
coarse, 150-mL, fritted glass filter
was used for the hot filtration. This filtration should be performed quickly, as precipitates
form rapidly upon cooling. This filtration may be performed in the air without complication.
5. The product is very hygroscopic and should be handled under an
inert atmosphere. The checkers found that inactive material was produced if the filtration
was performed using a
150-mL fritted funnel under a blanket
of
nitrogen. The checkers subsequently performed this filtration
under
nitrogen using a
Schlenk filtration system
consisting of a
2-L, 24/40 three-necked flask, a
24/40
double male adapter, and a
400-mL 24/40 coarse fritted Schlenk
filter. The reaction vessel is connected to one end of the double male
adapter and the other end is quickly attached to the Schlenk filter system under a
positive flow of nitrogen. The solution is poured onto the filter, and filtered into
the three-necked flask via a vacuum system that is connected to one of the ports on
the three-necked flask.
6. This step may be performed by using a
rotary evaporator
connected to a
water aspirator, with a drying column inserted
between the aspirator and the evaporator. The rotary evaporator is vented with
nitrogen
once the desired final volume is reached.
9. The recovered InI
3 can be used without further purification
to generate additional InI. Procedure B was repeated with recovered
InI3
(14.4 g, 29.1 mmol),
indium
powder (1.7 g, 14.8 mmol) and degassed
xylenes (320 mL) to yield
5.0 g (
95%)
of
indium(I) iodide
and
10.0 g (
93%) of recovered
indium(III)
iodide.
13. The separation is achieved on a column of
silica
gel with
pentane:ether (gradient
18:1 to 9:1) as the eluent.
14. The physical properties are as follows:
[α]D20−16.4° (CHCl3, c
2.8);
1H
NMR (300 MHz, CDCl
3) δ: 1.04 (s, 9 H), 1.16 (d,
3 H, J = 6.9), 2.72 (m, 1 H), 3.70 (s, 3 H), 3.73
(dd, 1 H, J = 9.9, 5.7) 3.84 (dd, 1 H, J = 9.9, 6.9), 7.36-7.46
(m, 6 H), 7.65-7.68 (m, 4 H); IR (film) cm
−1: 3071, 3050,
2955, 1746, 1111. Anal. Calcd for
C
21H
28O
3Si; C, 70.74; H, 7.92. Found: C, 70.73; H,
7.80.
15.
Hexane
was dried by storage over activated
4 Å molecular sieves.
16. The submitters indicated that 1.1 equiv of DIBAL-H was the optimal
stoichiometry to ensure complete consumption of the starting methyl ester. If less
was used, the aldehyde was not readily obtained in pure form. Excess DIBAL-H results
in ≈5-10% overreduction to afford a small amount of the alcohol. However, the
checkers found that the reaction did not go to completion under these conditions,
and that it was very difficult to separate the aldehyde product from the ester starting
material. Therefore, the checkers used 1.13-1.15 equivalents of DIBAL-H for complete
reaction, and obtained the product aldehyde in 85-86% yield along with 12-13% yields
of alcohol from overreduction. The checkers also obtained small amounts of ester
1
(2-5%, depending on the batch of DIBAL-H used). Ester
1 can be visualized by
TLC (R
f 0.65,
5% ether/
pentane), versus Rf's = 0.40 for the
starting ester and product aldehyde (which do not separate under these conditions).
17. The biphasic mixture should be stirred until both layers are
clear upon settling.
18. The separation is achieved on a column of
silica
gel with
pentane:ether (gradient
18:1 to 9:1) as the eluent. If any methyl ester remains, the aldehyde can
be further purified by recrystallization from hexanes.
19. The physical properties are as follows:
[α]D20−24.7° (CHCl3, c
1.5);
mp 63-64°C;
1H NMR (300 MHz,
CDCl
3) δ: 1.04 (s, 9 H), 1.10 (d, 3 H, J = 6.9),
2.57 (m, 1 H), 3.84 (dd, 1 H, J = 10.5, 6.3), 3.91
(dd, 1 H, J = 10.5, 5.4), 7.37-7.47 (m, 6 H), 7.63-7.66
(m, 4 H), 9.77 (d, 1 H, J = 1.2). Anal. Calcd for C
20H
26O
2Si:
C, 73.57; H, 8.03. Found: C, 73.30; H, 7.93.
20.
(R)-(+)-3-Butyn-2-ol
was purchased from Aldrich Chemical Company, Inc., or DMS
Fine Chemicals Inc.
21. Concentration of the crude mesylate under reduced pressure must
be done with care to avoid loss of product due to volatility.
22. The physical properties are as follows:
[α]D20+108.4° (CHCl3, c
2.39);
1H
NMR (300 MHz, CDCl
3) δ: 1.66 (d, 3 H, J = 6.8), 2.70
(d, 1 H, J = 2.0), 3.12 (s, 3 H), 5.29 (qd, 1 H, J = 6.8,
2.0);
13C
NMR (75 MHz, CDCl
3) δ: 22.3, 39.0, 67.4,
76.6, 80.1.
23. The checkers found that the mesylate is unstable to storage and
gave best results in the subsequent reaction with In(I)I if used immediately after
preparation.
24.
PdCl2(dppf) was
prepared according to the published procedure
2
from
PdCl2(NCPh)2 and dppf ligand
purchased from Aldrich Chemical Company, Inc. The
commercially available
PdCl2(dppf)
catalyst was also used, but the freshly prepared catalyst proved superior.
25. TLC analysis was performed on
silica
gel plates developed with
hexanes:ether (3:1),
R
f = 0.47, and visualized with
ceric(IV)
sulfate/
ammonium molybdate
stain.
26. The separation is achieved on a column of
silica
gel (34 cm × 16 cm) with
hexanes:ether (9:1)
as the eluent.
27. The physical properties are as follows:
[α]D20−17.0° (CHCl3, c
1.51);
1H
NMR (300 MHz, CDCl
3) δ: 0.86 (d, 3 H, J = 6.9), 1.07
(s, 9 H), 1.33 (d, 3 H, J = 7.5), 2.06 (m, 1 H),
2.15 (d, 1 H, J = 2.4), 2.71 (m, 1 H), 3.42 (m, 1
H), 3.44 (d, 1 H, J = 1.5), 3.71 (dd, 1 H, J = 10.2, 6.9),
3.78 (dd, 1 H, J = 10.2, 4.2), 7.37-7.46 (m, 6 H), 7.72-7.67
(m, 4 H); IR (film) cm
−1:
3493, 3305, 2931;
13C NMR (75 MHz, CDCl
3) δ:
13.5, 17.9, 19.1, 26.8, 30.2,
38.9, 68.6, 70.2, 78.1, 85.0,
127.8, 129.8, 132.9, 135.6.
Anal. Calcd for C
24H
32O
2Si: C, 75.74; H, 8.47. Found:
C, 75.74; H, 8.43.
28. The (2R,3R,4R) diastereomer results from partial racemization
of one or both of the allenylmetal intermediates. This point was confirmed by comparison
to authentic material as the (S)-MPA (
(S)-(2-methoxy)phenylacetic acid-Mosher's
acid) derivative. The optical rotations of these compounds are small, and thus correlation
by comparison of [α]
D20 values is unreliable.
All toxic materials were disposed of in accordance with "Prudent Practices in the
Laboratory"; National Academy Press; Washington, DC, 1995.
3. Discussion
The present procedure combines the second and third steps, thus avoiding handling
of the hygroscopic intermediate In2I4 complex. It also demonstrates
efficient recycling of the recovered InI3 etherate. Commercial InI, available
from Aldrich Chemical Company, Inc., can be used in the allenylindium procedure with
comparable results but at greater expense. The InI prepared as described is an easily
handled free-flowing powder, whereas the commercial product consists of small beads
that must be crushed before use.
Appendix
Chemical Abstracts Nomenclature (Collective Index Number);
(Registry Number)
Indium (I) iodide: Indium iodide
(8); Indium iodide (InI) (9); (13966-94-4)
(2R,3S,4S)-1-(tert-Butyldiphenylsilyloxy)-2,4-dimethyl-5-hexyn-3-ol:
5-Hexyn-3-ol, 1-[[(1,1-dimethylethyl)diphenylsilyl]oxy]-2,4-dimethyl-, (2R,3S,4S)-
(14); (220634-80-0)
Indium (III) iodide: Indium iodide
(8); Indium iodide (InI3) (9); (13510-35-5)
Indium (8, 9); (7440-74-6)
Iodine (8, 9); (7553-56-2)
(R)-3-(tert-Butyldiphenylsilyloxy)-2-methylpropanal:
Propanal, 3-[[(1,1-dimethylethyl)diphenylsilyl]oxy]-2-methyl-, (2R)-
(12); (112897-04-8)
Methyl (R)-(−)-3-hydroxy-2-methylpropionate:
Propanoic acid, 3-hydroxy-2-methyl-, methyl ester, (R)- (10);
(72657-23-9)
N,N-Dimethylformanide: CANCER SUSPECT AGENT: Formanide,
N,N-dimethyl- (8, 9); (68-12-2)
Imidazole (8); 1H-Imidazole (9);
(288-32-4)
tert-Butyldiphenylchlorosilane: Silane, chloro(1,1-dimethylethyl)diphenyl-
(9); (58479-61-1)
Methyl (R)-3-(tert-butyldiphenylsilyloxy)-2-methylpropionate:
Propanoic acid, [[(1,1-dimethylethyl)diphenylsilyl]oxy]-2-methyl-, methyl
ester, (2R)- (13); (153775-90-7)
Diisobutylaluminum hydride: DIBAL-H: Aluminum,
hydrodiisobutyl- (8); Aluminum, hydrobis(2-methylpropyl)-
(9); (1191-15-7)
(R)-3-Butyn-2-yl methanesulfonate: 3-Butyn-2-ol,
methanesulfonate, (2R)- (12); (121887-95-4)
(R)-(+)-3-Butyn-2-ol: 3-Butyn-2-ol, (+)-
(9); (42969-65-3)
Triethylamine (8); Ethanamine, N,N-diethyl-
(9); (121-44-8)
Methanesulfonyl chloride (8, 9); (124-63-0)
Hexamethylphosphoramide: HIGHLY TOXIC; CANCER SUSPECT
AGENT: Phosphoric triamide, hexamethyl- (8, 9); (680-31-9)
[1,1'-Bis(diphenylphosphino)ferrocene]dichloropalladium:
Palladium, [1,1'-bis(diphenylphosphino)ferrocene-P,P']dichloro-
(10); (72287-26-4)
Bis(benzonitrile)dichloropalladium(II): Palladium,
bis(benzonitrile)dichloro- (8, 9); (14220-64-5)
1,1'-Bis(diphenylphosphino)ferrocene (dppf):
Phosphine, 1,1'-ferrocenediylbis[diphenyl- (8); Ferrocene,
1,1'-bis(diphenylphosphino)- (9); (12150-46-8)
(2R,3R,4R)-1-(tert-Butyldiphenylsilyloxy)-2,4-dimethyl-5-hexyn-3-ol:
5-Hexyn-3-ol, 1-[[(1,1-dimethylethyl)diphenylsilyl]oxy]-2,4-dimethyl-, (2R,3R,4R)-
(14); (220634-81-1)
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