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Configurational Stability of Vinyllithium Derivatives with 1-Trimethylsilyl and 1-Alkoxy Substituents.

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converted into SAMP-hydrazones (S)-2, which are metalated with lithium diisopropylamide (LDA) in ether and alkylated with dimethyl sulfate or alkyl bromides to give 3.
According to ‘H-NMR shift experiments [methoxy singlet,
Eu(fod),], the diastereomeric excess (de) is greater than
95%. Reduction with catecholborane (CB) in ether leads to
the hydrazines 4, whose reductive N-N cleavage with Raney nickellhydrogen in methanol affords the p-substituted
primary amines 5 in good overall yields (41-63%) (Table
1). (S)-2-methoxymethylpyrrolidine [(S)-6],which is also
formed in this reaction, permits, after being separated off,
the recovery of the chiral auxiliary SAMP14] by nitrosatiodreduction or N-amination with KOCN/Hofmann degradationrS1.The enantiomeric excesses of the amines 5
(ee 395%) are consistent with the de values obtained at the
hydrazone stage 3. They were determined polarimetrically
( 5 e ) and NMR spectroscopically via the 3,3,3-trifluoro-2methoxy-2-phenylpropionamides(MTPA)16] (I9F, ‘H) and
by shift experiments with Eu(hfc),.
a 3 - 9 7 ~I ~F
o c H 3
- -RON0
- _/
21 R’X
R’ and R2.This “opposite enantioselectivity by synthon
control” is demonstrated in Table 1 for the enantiomeric
pairs (S)-5a/(R)-5aand (S)-5b/(R)-5b. The absolute configurations of the new, optically active amines 5a-d follow
from the known selectivity in SAMP-hydrazone alkylationd’]; the absolute configuration of (+)-5e was already
kno wn[’].
The novel method of a-alkylation/reductive amination
of aldehydes via SAMP-hydrazones[” thus opens up an efficient and general entry to both optical antipodes of psubstituted amines 5 of high enantiomeric purity[”,”1.
Received: February 15, 1984 [Z 709 IE]
German version: Angew. Chem. 96 (1984) 368
[I] Review: D. Enders, “Afkylutionof Chirul Hydruzones”, in J. D. Morrison: Asymmetric Synthesis, Vol. 3, Academic Press, New York 1984, p.
[2] a) D. Enders, H. Eichenauer, Chem. Ber. 112 (1979) 2933; b) D. Enders,
H. Eichenauer, U. Baus, H. Schubert, K. A. M. Kremer, Tetrahedron 40
(1984), in press.
[3] D. Enders, K. Papadopoulos, Tetrahedron Lett. 24 (1983) 4967.
141 SAMP and its enantiomer RAMP are also commercially available.
[5] D. Enders, P. Fey, H. Kipphardt, unpublished results.
[6] J. A. Dale, H. S. Mosher, J . Am. Chem. SOC.95 (1973) 512.
171 H. Biere, C. Rufer, H. Ahrens, 0. Loge, E. Schroder, J. Med. Chem. 17
(1974) 716.
[S] Procedure: To a solution of 20 mmol LDA (from 12.5 mL 1.6 M n-butyllithium in n-hexane and 2.9 mL diisopropylamine) in 20 mL ether is added 20 mmol (S)-2 under argon at 0°C and the mixture stirred for 4-5 h.
After cooling to - 120°C, the mixture is treated dropwise with R’X, stirred for a further 3 h, and then allowed to warm to room temperature
(RT).Work-up and distillation affords the hydrazones 3, which are dissolved in 50 mL ether and treated under argon at 0°C with two equivalents of CB. Warming to RT within I2 h, washing with water and several
times with 1 N NaOH, drying over MgS04, removal of solvent, and
short-path distillation, affords the hydrazines 4. These are dissolved in
methanol (50 mL) and hydrogenated in a Parr hydrogenation apparatus
with freshly prepared alkaline Raney nickel [9]/Hz (3.5-3.8 bar, 2040°C). After filtering off the catalyst, the filtrate is evaporated down,
taken up in 50 mL ether, refiltered, treated with 1.5 equivalents ofp-nitrobenzaldehyde, and stirred for 12 h at RT. The Schiff bases that are
formed (Rr20.9) are separated from (S)-6 (RrG0.2- +recycling) by column chromatography (SO2, ether); their ethereal solution (50 mL) is
stirred with 50 mL 1N HC1 for 2 h. The aqueous phase is separated off,
covered with a layer of ether (50 mL), and rendered alkaline with KOH
pellets. After shaking, the ether phase is dried over MgS04, evaporated
down, and the amines are distilled.
[9] Orgunikum, VEB Deutscher Verlag der Wissenschaften, Berlin 1977.
[lo] All new compounds gave correct elemental analyses and characteristic
spectra (IR ’H-NMR, MS).
[l 11 Enantioselective synthesis of a-substituted amines by asymmetric reduction or C N addition to SAMP/RAMP hydrazones: D. Enders et al., unpublished.
Table I. Primary amines 5 prepared via SAMP-hydrazones from aldehydes 1
by alkylation/reductive amination.
yield (neat)
n-C6H,3 CH3
100-110/15 52
(CH&CH(CH& 74/15
n-C9H19 CH3
78-84/13 53
- 8.4”
- 9.6’
[a] Data for short-path distillation. [b] According to NMR spectroscopic determination (MTPA-amides) ee > 95%. [c] Alkylation in tetrahydrofuran. [d]
[a]g (c=1.8, EtOH). [el [a]$? (c=l.l, C6H6). [fl [a]$? (c=1.0, EtOH); (S)-5e
[7]: [alg= -33” (c= 1.0, EtOH) corresponding to 96% ee.
Configurational Stability of
Vinyllithium Derivatives with
1-Trimethylsilyl and 1-Alkoxy Substituents**
By Rudolf Knorr* and nerese uon Roman
Considerable preparative
has been directed
towards vinyllithium derivatives with ~ilyl[’-~]
and alk o ~ y [ ’ , ~functions
in the a-position. Qualitative observations on 1-silyl-1-alkenyllithium compounds (1, R’ = R3Si,
R2# H) indicate that the E/Z-isomerization (a + b) in alkane solvents in the presence of 1,2-bis(dimethylamiI*]
Depending on the choice of nucleophilic and electrophilic building blocks, the C-C coupling procedure permits both enantiomers of an amine 5 to be prepared with
high enantioselectivity by simply changing the priority of
0 Verlag Chernie GmbH, 0-6940 Weinheim, 1984
Prof. Dr. R. Knorr, DipLChem. T. Freifrau von Roman
Institut fur Organische Chemie der UniversitSLt
Karlstrasse 23, D-8000 Miinchen 2 (FRG)
[**I E/Z-Equilibria, Part 9. This work was supported by the Deutsche Forschungsgemeinschaft, the Fonds der Chemischen Industrie, and the Stiftung Vo1kswagenwerk.-Part 8: E. Lattke, R Knorr, Chem. Ber. 124
(1981) 1600.
0570-OU33/U4/0505-0366 $02.50/0
Angew. Chem. Znt. Ed. Engl. 23 (1984) No. 5
no)ethane (TMEDA) at
25 oCL3a1
or in diethyl ether
(EtzO) above - 35 oC[3b,c1
occurs rapidly; only at temperatures below -65°C is the configurational stability in ether[3c1and in tetrahydrofuran (THF)L2b3c1
sufficient for stereospecific syntheses, but detailed rate data are not known.
By direct observation of the E/Z-diastereotopomerization
l a + lbL6]using dynamic NMR spectroscopy, we have now
been able, for the first time, to determine the rate constants
and activation parameters.
H i
1- 4
The 'H-NMR spectrumLs1of a THF solution[71of l-trimethylsilylvinyllithium 1 exhibits the AB splitting pattern
of the olefinic CH2 group (Table 1). As the solution was
warmed to above room temperature, considerable line
broadening was observed which was found to be reversible
on cooling. Line-shape analysisLg1between
26 and
+70°C gave an activation enthalpy AHc=7.4 (+ 1.5)
kcal/mol and activation entropy AS' = - 32 (k4) cal K-'
mol-'. The half-life of the Z / E permutation in THF at
+48"C is therefore 0.11 s and, by extrapolation, ca. 0.515 min at -70°C.
At room temperature, solutions of 1 decompose slowly
(Table 1). In the absence of TMEDA, 1 cannot be generated in a similar way['' in pentane; rather, as with the ana(3,3-dimethyl-llogous (l-chlorovinyl)trimethylsilaneL1ol,
buteny1)trimethylsilane is formed in addition to tert-butyltrimethylsilane. In TMEDA (by-product, N,N-dimethylvinylamine) the half-life of the Z/E-diastereotopomerization
at 61 "C is considerably greater than 15 s. Since this solvent dependence and the previously mentioned activation
parameters of 1 are in accord with those of l-arylvinyllithium compounds["], an ionic mechanism, as proposed["'
for the latter compounds, involving stabilization of charge
by silicon[3c1can be presumed.
1-Alkoxy-1-alkenyllithiums R2HC=C(OAlk)LiL6] are
formed and react in THF below -78°C[4c,5a,b1
up to ca.
- 2O0CLSc1
with retention of configuration; we investigated
their previously unknown degree of configurational stability spectroscopically[8,'21.The positions of the 'H-NMR
signals of the vinyl protons of 1-ethoxyvinyllithium 2,
which show up as sharp singlets in ethereal solutions['3],
are consistent with the values
for 3 and are
strongly solvent-dependent (Table 1); up to 106"C, line
broadening does not occur in TMEDA, but rather decomposition is observed. Since (E)- 1-ethoxy-1-propene in the
E / Z mixture[I3'reacts considerably more rapidly with tertbutyllithium to afford 4a than the (2)-isomer to give 4b,
reduction of the amount of tert-butyllithium allows the selective formation of different E/Z-mixtures (1 :3 to 3 : 1) of
1-ethoxy-1-propenyllithium4. These ratios remain constant
for more than 13 days at +25"C in THF; therefore, the
compounds 4 (as well as 9 ) are stable with respect to Z / E isomerization.
We propose that the vanishingly small coupling constant
of 2 and the unusually strongly positive one of 1 are due
to the o-inductive effects of R' and Li, which operate in
opposite directions in 2 but in the same direction in l[l4].
Received: December 16, 1983;
revised: March 14, 1984 [Z 656 IE]
German version: Angew. Chem. 96 (1984) 349
Table 1. 'H-NMR data and stability of vinyllithium derivatives 1-4 in 0.050.5 M solutions, t / 2 = half-life of the decomposition.
6 ( ~ ' ) ~ ( H c ) ~J(H,H) 2/2
["Cl [a1
b THF/HMPT [b]
b THF/alkane [c]
b Et20/alkane [c]
b TMEDA/alkane [c, d] +25
b THF[e]
b Et20/THF [fl
b TMEDA [g]/alkane [h] +25
b C6D6/THF [g]
b [D8]THF/TMEDA [g, n] +25
5.48 [I]
5.44 [I]
4.45 [m] 4.32 [m] -
20 min
17 h
17 d
t15 h
% 2d
t 9d
t 17 h
[a] Assignments for 1-3 interchangeable. [b] With ca. 15 vol.-% hexamethylphosphoric triamide (HMF'T). [c] Ca. 57 VOI.-~/Opentanelhexane. [d] Same
NMR parameters at +61 and -32°C. [el Almost the same &values with 50
vol.-% pentane at +25 and -5O"C, with (CH30CH2)2or with 83 VO~.-~/O
TMEDA. [fl20 vol.-%. [g] One mol. equivalent. [h] 90 vol.-Oh pentane/hexane.
[i] Very broad. [k] Lit. [12a]. [I] q with 'J=6.5 Hz (E-isomer). [m] q with
re'J=6.0 Hz (Z-isomer). [n] Methyl doublets at S=1.57 (E) and 1.47 (Z),
Angew. Chem. Int. Ed. Engl. 23 (1984) No. 5
[I] Review: 0. W. Lever, Tetrahedron 32 (1976) 1943, especially p. 19581962.
[2] a) L. A. Paquette, G. J. Wells, K. A. Horn, T.-H. Yan, Tefrahedron 39
(1983) 913; b) L. E. Overman, T. C. Malone, J. Org. Chem. 47 (1982)
5297; c) R. 9. Miller, G. McGarvey, ibid. 44 (1979) 4623; d) T. H. Chan,
W. Mychajlowskij, 9. S. Ong, D. N. Harpp, ibid. 43 (1978) 1526; e) R.
Amouroux, T. H. Chan, Tetrahedron Left. 1978, 4453: f ) 9. T. Grobel, D.
Seebach, Chem. Ber. 110 (1977) 867; g) A. G. Brook, J. M. Duff, Can. J.
Chern. 51 (1973) 2024.
[3] a) R. F. Cunico, J. Organomet. Chem. 60 (1973) 219; b) A. G. Brook, J.
M. Duff, W. F. Reynolds, ibid. I21 (1976) 293; c) G. Zweifel, R. E. Murray, H. P. On, J . Org. Chem. 46 (1981) 1292.
141 a) C. E. Russel, L. S. Hegedus, J. Am. Chem. Soc. 105 (1983) 943; b) 0.
Miyata, R. R. Schmidt, Tetrahedron Lett. 23 (1982) 1793; c) R. R.
Schmidt, R. Betz, Synthesis 1982, 748; d) I. Hoppe, U. Schollkopf, Liebigs Ann. Chern. 1980, 1474; e) T. Yogo, A. Suzuki, Chem. Lett. 1980,
591; f ) E. E. Knaus, K. Avasthi, K. Redda, A. Benderly, Can. J. Chem.
58 (1980) 130; g) E. J. Corey, D. L. Boger, Tetrahedron Lett. 1978, 13; h)
J. R. Wiseman, N. I. French, R. K. Hallmark, K. G. Chiong, ibid. 1978,
3765; i) J. E. Baldwin, 0. W. Lever, N. R. Tzodikov, J. Org. Chem. 41
(1976) 2874, 2312.
[5] a) J. Hartmann, M. Stahle, M. Schlosser, Synthesis 1974, 888; b) R. Everhardus, R. GrBfing, L. Brandsma, Red. Trau. Chim. Pays-Bas 97 (1978)
69; c) J. A. Soderquist, A. Hassner, J. Am. Chem. Sac. 102 (1980) 1577.
[6] Compounds 1-4 are represented in simplified notation since neither
their crystal structures nor their degrees of association in solution are
[7] Experimental Procedure for 1: A solution of commercial (I-bromoviny1)trimethylsilane in 1.0 mL solvent is allowed to react with tert-butyllithium (1.5 M in pentane/hexane, 2.0 mmol) under N2 at -74°C until
reaction is complete (2 h) [2d, f, 3c]. The lithium ethenolate formed in
THF with tC4H9Li interferes in the spectroscopic investigation; solvent
is therefore removed at 12 torr (room temperature) from a solution of 1
in EtzO, and the residue is dissolved in THF at -25°C. Injection of tertbutyl alcohol at - 78 "C yields trimethylvinylsilane.
(81 Measured at 60 MHz after addition of ca. 15 vol. Yo (CH3)$3 using a
Varian HA-60 IL spectrometer.
[9] a) S. Alexander, J. Chem. Phys. 37 (1962) 967, and literature cited therein; b) G. Binsch, Top. Stereochem. 3 (1968) 97, see p. 113; c) Temperature dependence of the spectral parameters in ca. 0.4 M THF solution:
6(HL)=7.29+0.00046 ( T -298 K), 6(HC)=6.92+0.0017 ( T -298 K),
2J(H,H)=9.84-0.014 ( T -298 K).
[lo] R. F. Cunico, Y. K. Han, J. Organornet. Chem. 174 (1979) 247.
[Ill R. Knorr, E. Lattke, Tetrahedron Left. 2977, 3969.
1121 a) 'H-NMR of 3: J. A. Soderquist, G. J.-H. Hsu, OrganometaNics I
(1982) 830; b) "C-NMR of 2 : F. T. Oakes, J. F. Sebastian, J. Org. Chern.
45 (1980) 4959.
0 Verlag Chemie GmbH, 0-6940 Weinheim. 1984
0570-0833/84/0505-0367 $02.50/0
[ 131 Experimenfal Procedure for 2 and 4d4b (cf. [12a]): terf-Butyllithium
(15-18 mmol in pentane/hexane) is added dropwise to a solution of 1-
ethoxyethene (7.0 mmol) or of I-ethoxypropene (E/Z=28 :72) in 10 mL
THF (or 5.0 mL pentane with 7.0 mmol TMEDA) under an inert gas atmosphere at -74"C, the mixture allowed to warm slowly to room temperature, the solvent and educt removed at 12 torr/+25"C, and the residue taken up in fresh solvent. Signals of the regenerated enol ether (for
4d4b in the same E/Z ratio) appear in the 'H-NMR spectrum only
after addition of ferf-butyl alcohol.
1141 R. Knorr, Tetrahedron 37 (1981) 929.
Detection of Intramolecular
Linkage lsomerization of a (Pseudo)tetrahedral
Nickel(I1) Bis(chelate)**
By Rudolf Knorr* and Friedrich Ruf
one, and then a second, methyl singlet17b1
appear for 3 and
4, arising from incorporation of the p-tolyliminomethyl
groups into the chelate ring. In addition, a novel triplet for
the p-hydrogen atom of the previously coordinated phenylimino group is observed. Consumption of 2 is measured
by the reduction in intensity of the methyl signal of the
exocyclic tolylimino groups and the p-absorption of the
coordinated phenylimino
The final equilibrium
of 2, 3, and 4 corresponds to the statistical distribution
(1:4:4). The rate constant1'] k,,,=38(ltr5)~10-'s-' at
24.5 "( & 1)OC refers to only one of the four equally probable linkage isomerizations of 2. A parallel experiment using a twofold initial concentration yields the same value
within experimental error; in this inert solvent the isomerization is, therefore, a first order reaction[91.
The monomolecular interconversion of tetrahedral and
planar isomers of tetracoordinated nickel(r1) bis(che1ates)
such as 1 could proceed either as a thermally allowed,
synchronous process['] or, instead, in two steps involving
reversible opening of a chelate ring. We found that a
model (pseud0)tetrahedral nickel(1i) compoundI2l closely
related to 1 undergoes slow inversion of configuration at
25 0C13*41,
possibly involving transient formation of the planar (not detectable) form. We now wish to report that a
spontaneous chelate opening is possible, using evidence of
linkage isomerization of 2 to 3 and 4.
2 =
The very rapid formation of 2 from 1 permits an independent measurement of the rate constant under irreversible conditions. The 'H-NMR spectrum recorded immediately after mixing the nickel complex 1 (0.175 M) withptoluidine (3.73 M) in DCCI3 shows only the nickel complex 2. Intermediate products (e.g. 3) of the linkage isomerization may be present in only very small steady-state
concentrations, since they react immediately and almost
completely with the remaining p-toluidine to form 5 by
substitution of the now exocyclic phenylimino groups released from the chelate. The repeated interplay of bonding
isomerization and exocyclic substitution leads eventually
via three additional intermediateds1 to 6, the sole final
p r o d ~ c t [ ~ " The
- ' ~ ~increase
in intensity of the methyl signal
(6 = 26.6) for the coordinated p-tolylimino group at the
expense of that of the p-hydrogen signal of 2
( S = - 11.4)['*] was studied as a function of time and gave
k,,,=64(f20) x lO-'s-', assuming the same rate constant
for each of the conceivable linkage isomerizations. Within
the limits of experimental error, this value is consistent
with the forementioned rate constant and proves that free
p-toluidine does not measurably accelerate the linkage
Considering that the catalytically efficient donor property of p-toluidine should not be smaller than that of the
solvents used in the two experiments, we suggest that the
linkage isomerizations are initiated by monomolecular
rupture of the N'Ni bond in 2["].
Since the subsequent C2C3rotation presumably contributes to the free energy of activation (AG* = 26.0( zk 0.3)
kcal/mol) of the linkage isomerization, the similar values
of k,,, and the rate constant for inversion of configura-
Exchange of the two exocyclic phenylimino substituents
of 1['' for p-tolylimino substituents, leading to 2, is complete after less than 5 min at room temperaturel6'. The 'HNMR spectrum[7a1of a solution of the purified nickel complex 2 in CCI,/DCC13 (3 : 1) initially exhibits no extraneous signals; however, in the course of a few days at first
Prof. Dr. R. Knorr, Dr. F. Ruf
Institut fur Organische Chemie der UniversitBt
Karlstrasse 23, D-8000 Miinchen 2 (FRG)
Paramagnetically Induced NMR Shifts, Part 10. This work was s u p
ported by the Stiftung Volkswagenwerk, the Deutsche Forschungsgemeinschaft, and by the Fonds der Chemischen 1ndustrie.-Part 9: [5a].
Q Verlag Chemie GmbH, 0-6940 Weinheim, 1984
0570-0833/84/0505-0368 $02.50/0
Angew. Chem. Int. Ed. Engl. 23 (1984) No. 5
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trimethylsilyl, substituents, configuration, alkoxy, vinyllithium, derivatives, stability
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