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Carbonyl Olefinations with Methylenemolybdenum Reagents in Aqueous or Ethanolic Media.

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lytically pure crystals. After debenzylation of 5a via hydrogenation, delesserine 6, which exists in solution as an
equilibrium mixture of the bicyclic and monocyclic forms
[ I ] J. C. Yvin, A.-M. Chevolot-Magueur. L. Chevolot, J.-Y. Lallemand, P.
Potier, J. Gnilhem, J. Am. Chem. SOC. 104 (1982) 4497.
(21 H. Elmer, A. Liedmann, K. Oppers, Naunyn-Schmiedebergs Arch. Enp.
Pathol. Pharmakol. 190 (1938) 5 10.
131 D. Seebach, E. Hungerbiihler in R. Scheffold: Modern Synthetic Methods
1980, Vol. 2, Salle + Sauerlander, Frankfurt am Main Aarau 1980.
[4] E. Hungerbiihler, D. Seebach, Hehi. Chim. Acfa 64 (1981) 687.
[5] T. Mukaiyama, K. Suzuki, T. Ydmada, Chem. Left. 1982, 929.
[6] The debenzylation product of 5b, epi-delesserine, has the rotation
[a]dO=-2.7 under the same conditions.
[7] We wish to thank Dr. D. Hauser (Sandoz AG, Basel) for this test.
[8) A. J. Mancuso, S.-L. Huang, D. Swern, J. Org. Chem. 43 (1978) 2480.
+
Q
0I3 7,
1
'Q
2
OR2
6b
Carbonyl Olefinations with
Methylenemolybdenum Reagents in
Aqueous or Ethanolic Media**
By Thomas Kauffmann *, Petra Fiegenbaum, and
Raphael Wieschollek
Among the known transition metal reagents that have
been used for carbonyl ole fin at ion^'^,^^, the molybdenum
complexes first reported by US'^^,‘'^ deserve special attention, since they are the most easily accessible and are comparable in their carbonyl selectivity to the titanium-containing alkylating reagentsL4].
We report herein that the Mo-compounds 1 and 2 accessible according to Scheme I are-other than the titanium-containing Tebbe-reagent['"] and the structurally related Zr-reagents of Schwariz et al.[2h1-suitable for carbony1 olefination in aqueous or ethanolic solvents[51,which
could prove advantageous in the case of hydrophilic substrates.
lvlo0C1,
2 MeLi
d
0
II
c I-iVl0
(
112
(or d i n i e r )
iCfi,
1
2 MeLi
MoC1,
Cl~lVl<)-(112
(or d i m e r ) + <'Ill
Scheme I
Scheme I . Bz= benzyl. 1 : From methyl methoxyacetate and 4-benzyloxybenzyl bromide with lithium diisopropylamide (LDA) in tetrahydrofuran (THF),
-75"C, yield 86%-2: In four steps from diethyl ( +)-tartarateC4],40%.-3:
From 1 ( L D A i n THF, -75°C) and 2.-4: By Swern-oxidation [S] of 3 (dimethyl sulfoxide (DMSO), (COC1)2, Et3N, in CH,C12); 62% based on 2 . - 5 :
By hydrolysis of the acetonide protecting group (TsOH, MeOH) 91%. Separation of the two diastereomers by crystallization from etherlpentane; 5a
(35% of the mixture) crystallized (m.p. 144"C), 5b (65% of the mixture) remains in the mother liquor and is isolated as an oil.-6: From 5a by debenzylation with Pd/C in MeOH; 90% colorless, non-crystalline powder,
m.p.=105"C, [a]z,O= +44 (c=0.72, MeOH) [6] (natural product: +36 [I]);
ratio 6a16b (5 mg/mL CD30D): 63/37 ('H-NMR); I3C- and 'H-NMR data
of 6a and 6b agree with the values given in [I].
6a and 6b, was obtained. The identity of 6 was proven by
comparison of the sign and magnitude of its optical rotation and 'H-NMR data with the values reported in the literature"s61.Delesserine 6 possesses no anticoagulant properties in the Quick test"].
Received: March 12, 1984 [z 756 IE]
The reagent prepared in anhydrous tetrahydrofuran
(THF) (5 mmol in 50 mL) according to Scheme 1 is treated
with the carbonyl compound dissolved or suspended in
water, ethanol/water mixture, or ethanol (in each case ca.
20 mL) (Table 1). If this is carried out at -70 " C , the mixture is allowed to warm to room temperature within 12h; if
the addition is carried out at 0 "C, then the mixture is kept
at this temperature for 1 h.
Reactions with 1 : The yields of alkene (Table 1) on addition of the substrate in ethanol or ethanol/water at
-70 "C are practically the same as on addition of the substrate in anhydrous THF, with one exception: for some unknown reason 1 reacts better with benzaldehyde in the
presence of water or ethanol. Thus, as a rule, the carbonyl
olefination is more rapid than a replacement of the CI substituents in 1 by OEt or OH. If, however, water is added at
0 "C there is a distinct loss in reactivity.
Reactions with 2 : In ethanol or aqueous T H F the yields
of alkene are substantially lower than in anhydrous T H F
(Table 1). The drastic reduction in yield of alkene on addi-
German version: Anqew. Chem. 96 (1984) 498
CAS Registry numbers:
1, 74649-77-7: 2, 81028-12-8; 3 (isomer I), 90866-60-7; 3 (isomer 2), 9089980-2; 3 (isomer 3), 90899-81-3; 3 (isomer 4), 90899-82-4; 4 (isomer I), 9085888-1; 4 (isomer 2), 90899-52-8; 5% 90858-89-2; 5b, 90899-53-9; 6a, 8219878-5; 6b, 90899-54-0; methyl methoxyacetate, 6290-49-9; 4-benzyloxybenzyl
bromide, 5544-60-5
Angew. Chem. Inf. Ed. Engl. 23 (1984) No. 7
[*I Prof. Dr. Th. Kauffmann, P. Fiegenbaum, R. Wieschollek
Organisch-chemisches Institut der llniversitat
OrlBans-Ring 23, D-4400 Miinster (FRG)
[**I Transition Metal-Activated Organic Compounds, Part 15. This work was
supported by the Deutsche Forschungsgemeinschaft and the Fonds der
Chemischen 1ndustrie.-Part 14: [ I I.
0 Verlag Chemie GmbH, 0-6940 Weinheim, 1984
0570-0833/84/0707-0531 $ 02.50/0
53 1
tion of ethanol in the reaction with heptanal can be ascribed, in part, to the fact that its diethyl acetal 4 (13%) is
formed. Since 4 is undoubtedly formed via a semiacetallike intermediate and a lot of heptanal is recovered after
hydrolysis, presumably some of the heptanal of the carbonyl olefination is removed by formation of 3.
Since 1 and 2 are relatively insensitive towards compounds containing OH-groups, it was expected that hydroxyaldehydes can be readily olefinated with these reagents. The reaction 5 - 6 does indeed proceed quite
smoothly in anhydrous THFI6].
Received: February 21, 1984 [Z 716 IE]
German version: Angew Chem. 96 (1984) 500
3
4
Table I. Carbonyl olefinations in T H F with added EtOH, H 2 0 or EtOH/
H 2 0 . Molar ratio of reagent: carbonyl compound=2: 1, in competition reactions 2: 1 :1. Yields in brackets refer to the reaction in anhydrous THF.
Reagent
Carbonyl
compound
Added
solvent
1
1
1
1
Ph-CHO
Ph-CHO
4-MeO-C6H,-CH0
4-MeO-C6H4-CHO
1
1
1
4-Me0-C6H4-CHO
C6HI,-CH0
Ph-CO-Me
4-MeO-C6H4-CHO
EtOH
H20
EtOH
EtOH/
H20(4:6)
H20
EtOH
EtOH
+
2
2
2
2
Ph-CO-Me
Ph-CHO
Ph-CHO
4-MeO-C6H4-CHO
C6HnCHO
Yield [Yo]
T ["C] Alkene
Recovered
[a1
carbonyl
compound
-70
0
-70
-70
0
-70
-70
EtOH
-70
EtOH
H20
EtOH
EtOH
-70
0
-70
-70
90(20)
50
92 (93)
83
l(4)
22
0 (0)
5
55
23 (25)
48 (49)
62/1 [b]
16
0 (0)
47 (39)
12/87
(63/1)
36 (65)
31
41 (84)
10 (65)
(10160)
46 (30)
61
56 (3)
59 (25)
[a] Referred to carbonyl compound used. Determined gas-chromatographically. [b] Preferred olefination of the aldehyde.
Stability of 1 and 2 toward protic solvents: We treated
the THF solution of these reagents with 20 mL ethanol or
water, added a carbonyl compound after prescribed times,
and determined the yields of alkene. As shown in Figure 1,
1 and 2 are still rather active after 30 min at 0 "C and 30
min at -70 "C, respectively, despite a large excess of
water (molar ratio: HzO:l =220: 1) or ethanol (C2HSOH:2
= 70: 1). According to the activity curve a new stable species is formed from 2.
Yield of alkene
0
N
s
[%I
-
Fig. 1. Loss of reactivity of 1 (-)
and 2 (----) on addition of H 2 0 or
ethanol, respectively; reactions of 1 with 4-MeO-C6H4-CH0 at 0 ° C and of
2 with Ph-CHO at -70 "C, respectively. Points on the ordinates: protic solvent and carbonyl compound given simultaneously.
0 Verlag Chemie GmbH, 0-6940 Weinheim, 1984
[I] Th. Kauffmann, M. Bisling, Tetrahedron Lett. 25 (1984) 293.
[2] a) F. N. Tebbe, G. W. Parshall, G. S. Reddy, J. Am. Chem. SOC.100 (1978)
3611; b) F. W. Hartner, Jr., .I. Schwartz, ibid. 103 (1981) 4979; c) Th.
Kauffmann, B. Ennen, J. Sander, R. Wieschollek, Angew. Chem. 95 (1983)
237; Angew. Chem. Int. Ed. Enyl. 22 (1983) 244; d) Th. Kauffmann, G.
Kieper, ibid. 96 (1984) 502 and 23 (1984) 532.
131 The carbonyl olefinations with a Nb- and a Ta-reagent described by R. R.
Schrock, J. Am. Chem. SOC.98 (1976) 5399, gave poor yields.
[4] M. T. Reetz, Top. Curr. Chem. 106 (1982) I ; D. Seebach, B. Weidmann, L.
Widler in R. Scheffold: Modern Synthetic Methods 1983, Salle, Frankfurt
1983.
[5] Carbonyl olefinations in aqueous medium were first observed by R. Wieschollek (Universitat Munster).
[6] Procedure: 6 : Dissolution of MoC15 (1.37 mg, 5 mmol) in anhydrous
T H F at room temperature leads (within 2 h) to formation of the complex
(THF)2MoOCI, [7]. The solution is stirred with 10 mmol MeLi (ca. 1.5 M
in ether) at -70°C for 1.5h and then treated with 305 mg (2.5 mmol) ohydroxybenzaldehyde. The mixture is allowed to warm to room temperature within 12h, hydrolyzed with 20 m L water, and rendered neutral with
NaHCO,. The aqueous phase is extracted three times with 20 mL hexane.
The combined organic phases are shaken with a K,[Fe(CN),] solution
(2 g in 20 mL H 2 0 ) to give a water-soluble Mo-complex, washed twice
with water, and dried. After evaporation to dryness, the alkene is separated by column chromatography (silica gel, 13 x 4 cm, CHCI,); yield 228
mg (76%).
[7] C. A. McAuliffe, A. Werfali, Inorg. Chim. A d a 60 (1980) 87.
Selective Synthesis of
Carbonyl Olefinating or Alkylating Reagents
from MoCl, and MeLi
by Changing the Solvent or the Rate of Addition
of MeLi**
By Thomas Kauffmann* and Gudrun Kieper
Reaction of methyllithium (MeLi) with MoCI,,
(Et0)3MoC1z or O=MoCI, leads to the formation of carbonyl olefinating reagents1''21.We have now found, in the
case of MeLi and MoCI, , that the rate of addition of MeLi
and the solvent have a surprisingly marked influence on
the product pattern.
Reactions in tetrahydrofuran (THF): When a solution of
3 or 4 mol equivalents of MeLi in diethyl ether (ca. 1.5 M
solution) is added dropwise and slowly (1 drop per 7-10 s)
to a solution of MoCI, ( 5 mmol) in THF (ca. 40 mL) under
argon at -70 "C and the mixture is kept at this temperature
01
I
532
CAS Registry numbers:
1, 84809-63-2; 2, 84809-61-0; 4, 6138-82-4; 5, 90-02-8; 6, 695-84-1; MoOCII,
13814-74-9; MoCI,, 10241-05-01; I'hCHO, 100-52-7; 4-MeOC6H4CH0, 12311-5; CH,(CHz),CHO, 111-71-7; I'hC(O)CH,, 98-86-2; PhCH=CH2, 100-425; 4-MeC6H4CH=CH2, 637-69-4; CHZ=CH(CH2)5CH,, 111-66-0;
PhC(CH,)= CHz, 98-83-9
[*I Prof. Dr. Th. Kauffmann, G. Kieper
Organisch-chemisches Institut der Universitat
Orleans-Ring 23, D-4400 Miinster (FRG)
[**I Transition Metal Activated Organic Compounds, Part 16. This work was
supported by the Deutsche Forschungsgemeinschaft and the Fonds der
Chemischen 1ndustrie.-Part 15: [I].
0570-0833/84/0707-0532 $ 02.50/0
Angew. Chem. Int. Ed. Engl. 23 (1984) No. 7
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