вход по аккаунту


Asymmetric Michael Additions to Chiral -Unsaturated Alkoxycarbene Chromium Complexes.

код для вставкиСкачать
any symmetry constraints. Stationary points were characterized rigorously by
computing vibrationnl frequencies. Minima have no modes uith an imaginary
frequenc), while transition btructure? have one and only one xibration with an
iinaginxy frequency.
[I21 Optimized structural data for prototypical transition states for CCI, addition
to ethylene are quite similar at AM1 and a b initio (3-21G) levels [13h]. We
have also found that A M 1 transition state energetics correctly reproduce the
observed facial selectivities i n CCI, additions to X-methylenetricyclo[3.2 1 .02-i]octai~es reported by R. VV! Hoffniann. N . H;iiicl. B Landmanii.
(7rcrrr B r ) . 1983. 116. 3XY.
[13] a ) R. Hoffinann. ./. Ani. Chon. Soc. 1968. 90. 1475. b) A b initio calculations on
model systems confirm the qualitative predictions: 3-21G: K N Houk. N . G.
Rondan. J. Mareda. l i , / r d ~ & o n 1985. 41, 1563. MP2,6-31G*: J. F. Blake. S G.
Wiervhke. W. L. Jorgensen. J. A m . C/rlw. SIK 19119. ill. I Y I Y .
[I41 Ah initio calculations (3-21G)o n the AM1 transition structures for CCI, addition t o 2a support thegeneral conclusions. Total energies [Hartree] for . \ Y W and
unrr-facial addition structures: - 1429.11927 and .- 1429,12620 for C7 tipproacli. - 1429.12650 and - 142Y.12433for C-X ;ippro;ich. reqpectively Thus,
the former structures are energetically livored. Further. 5 i w t k e attack is
preferred to a grcater extent in the transition structures corresponding to C7
approach (1.9 L S 1.4 kcalinol-' for C8 approach)
Asymmetric Michael Additions to Chiral
a$-Unsaturated Alkoxycarbene Chromium
Complexes **
Prof. Dr. J. Barluenga. J. M. Montaerrat. Dr. J Florez
Instituto Universitario de Quimica Organometilica €nEnr.iyue Mo/c,.\
Universidad de Oviedo
J u l i i n Claveria, 8. E-33071 Oviedo (Spain)
Telefax. In[. code (348)5103446
Dr. S. Garcia-Grunda."' E. Martin"'
Depirtamento de Quimica Fisica y Analitica
Facultad dc Quimica, Universidad de Oviedo (Spain)
['I X-ray crystal structure analyses
[**I This work was supported by Direccibn General de Investigacion Cientifica y
Tecnica (DGICYT) (Grant PBXU-0538). J. M. M. thanks the Ministerio de
Educacibn y Ciencia de Espa~iafor a doctoral fellowship.
3a : R' = 2- furyl, 70%
3b : R' = Ph. 65%
Scheme 1 Synthesis of chiral carbene complexes 3. TMS
we synthesized the (-)-8-phenylmenthol-derived vinykarbenes
31q1(Scheme 1). The synthesis of these chiral carbene complexes
was achieved starting from the tetramethylammonium complex
l [ l o l by alkylation[' ' I and condensation.""
The reaction of the
organolithium reagent 4[13] (R2 = CH,=CHCH,) with the
vinylcarbene complex 3a (R' = 2-furyl) led to the acyclic 1.4-addition product 5a (Scheme 2) with good diastereoselectivity
(95% do; Table 1 . entry 1): but the expected['] intramolecular
Jose Barluenga,* Javier M. Montserrdt, Josefa Florez,
Santiago Garcia-Granda, and Eduardo Martin
The Michael reaction is one of the fundamental processes for
carbon-carbon bond formation; and significant advances in
asymmetric 1.4-conjugate addition reactions, involving chirally
modified substrates or a chiral reaction medium, have been
achieved."] x,b-Unsaturated Fischer carbene complexes. which
are increasingly playing an important role in organic synthesis,[*]
behave as reactive Michael acceptors. Since the pioneering work
by Casey et al. on additions[31of carbon nucleophiles, several
other nucleophiles have been 1,4-added to heteroatom-stabilized
alkenyl-[41and aIkynylcarbene['] complexes with good regioselectivities and diastereoselectivities;[bl but thus far no examples
of enantioselective Michael additions to a.P-unsaturated Fischer
carbene complexes are known. The asymmetric Michael reactions of chiral prolinol-derived aminocarbene complex anions to
cyclic enones have been recently described.['] We report herein
on highly diastereoselective conjugate additions of B-oxygenfunctionalized organolithium compounds, alkyllithium reagents,
and lithium enolates to chirally modified a.P-unsaturated alkoxycarbenechromium complexes that are readily available in optically pure form.
In a previous reportrs1we described the diastereoselective onepot synthesis of strained tricyclic ethers by reaction of properly
substituted P-oxygen-functionalized organolithium compounds
with Fischer vinylcarbene complexes. In order to prepare these
unusual tricyclic structures as enantiomerically pure compounds
2. Silica gel
5a : R' = 2- firryl. R2 = CH2CH=CH2.38%
5b : R' = R 2 = Ph, 59%
Ph Ph
"*, Ph
MeOH, 25°C
(R' = R2 = Ph)
Scheme 2. Asymmetric Michael additions of B-oxygen-substituted oreanolithium
compounds. R*OH = ( -)-8-phenylmenthol.
Table 1. Asymmetric Michael additions of organolithiuin compounds to optically
active carbene complexes 3.
Entry R'
R3 Product Yield
82 [fl
82 [h]
88 [h]
de [c]
I " / . ] [%I
87 [g]
90 [I]
80 [I]
b],, [d] Config. [el
-23 s
-97 R
[a] Michael adduct used in each cdse to determine the enantiomeric excess.
[b] Yield of isolated product after flash chromatography based on the corresponding carbene complexes 3. [c] Determined by ' H NMR spectroscopy (300 MHz) and
further confirmed by HPLC analysis (Nucleosil 120-10. hexane:THF. 15-36:l)
[d] Optical rotations were recorded i n CH,CI, at 20-25 'C. c = 0.25-0.35 g
100 mL- '. [el Absolute configuration of the new stereogenic center formed in the
addition step. Determined by X-ray analyses of compounds 8 a and IZa (entries 3.
6) and proposed by analogy in all the other adducts assuming the same stereocheinical model. [f] Based on enol ether 6.[g] Determined by HPLC (Chiralcell OD-H.
hexane: 7-propanol. 3 : 1) of compound 7 in comparison with the corresponding
racernic mixture. [h] Based on the corresponding enol ether Yb. 9c. [i] Determined
by HPLC (Chiralcell OD-H. hexane:THF, 6- 12: 1) of 2.4-dinitrophenylhydrazone
derivatives of the corresponding aldehydes 10 in comparison with the corresponding
racemic products.
alkoxide exchange and cyclopropanation reactions were not observed. probably due to the bulkiness of the 8-phenylmenthyl
group. While this approach has so far not led to tricyclic ring
the high asymmetric induction observed in the reaction prompted us to study the addition of other organolithium
compounds and these results represent the first examples of
asymmetric conjugate additions to Fischer vinylcarbene complexes.
Scheme 2 shows the Michael reaction of another [j'-oxygenfunctionalized organolithium 4 (R2 = Ph) with carbene complex
3 b ( R ' = Ph) which gave, after purification by silica gel chromatography. adduct 5 b. Removal of the pentacarbonylchromium fragment by basic treatment with sodium methoxide" in
methanol. afforded the less stable (Z)-enol ether[3c16 ( J = 6 Hz,
vinyl protons). The (- )-8-phenylmenthyl chiral auxiliary was
removed and recovered (80 %, after column chromatography)
by acid hydrolysis ( 1 N, HCI) of 6 which led to the cyclic hemiacetal 7 as a single product (Table 1 , entry 2), indicating high
asymmetric induction in the conjugate addition and also in the
intramolecular cyclization reaction. The relative configuration
of the newly formed stereogenic carbon centers of 7 was established by analysis of the coupling constants for the methine
protons and by a difference NOE experiment. Under the same
reaction conditions, the addition of alkyllithiurn reagents to cQunsaturated carbene complex 3 b led diastereoselectively to the
Michael adducts 8. Removal of the transition metal moiety and
the chiral auxiliary as previously described gave rise to the optically active p-substituted aldehydes 10 with high enantiomeric excesses (Scheme 3, Table 1. entries 3 - 5 ) . Both vinyl ethers 9 were
1. RZLi
2. Silica gel
OR* Ph
p R 2 11
R3 + 2 5 T
2. Silica gel
( c 0 ) 5 c r w R 2
MeOH, 25'C *
(Rz= Ph, R3 = H)
12a : RZ=Me, R3 = H
12b : Rz = Ph, R3 = H
12c : R2,R3= (CHz),
OR* Ph
[a]*= c1.8 (c = 0.50, CH2CIz)
Scheme 4. Asymmetric Michael additions of lithium enolates of ketones
OR* Ph
* (CO)@
MeOH, 25'C
8b : Rz = Bu
8c : R2= rBu
OR* Ph
THF. 2 5 T
9b : 76%
9c : 45%
Scheme 3 Asymmetric Michael additions of alkyllithium compounds. Yields of 9b
and 9 c are based on 3b: both vinyl ethers are a mixture Z : E , 6.1.
Fig. 1. Crystal structure of 8 a Selected bond lengths [A] and bond angles [ 1:
Cr(1)-C(1) 2.056(7). O(l)-C(l) 1.288(6), C(I)-C(Z) 1.528(8). C(2)-C(3) 1.528(&),
C(3)-C(7) 1.476(9), C(3)-C(4) 1.563(11); C(l5)-Cr(l)-C(1)172.8(4). C( 1)-0(1)C(18) 125.2(5), O(l)-C(l)-C(2) 103.4(5).
isolated as a 6: 1 mixture of diastereoisomers ( Z :E ratio determined from the ' H N M R spectrum; Jcis = 6.9 Hz, J,,,,
= 12.1 Hz, vinyl protons). The lithium enolates 11, generated
from the corresponding ketones by treatment with lithium diisopropylamide (LDA) at -78 "C in tetrahydrofuran,["] may also
be added as donors to the optically active acceptor 3 b, yielding
the 1.4-adducts 12 in uniformly high diastereomeric excesses
(Table 1. entries 6-8). The Michael addition of the lithium enolate of cyclohexanone to Fischer vinylcarbene complexes takes
place with syrz diastereoselectivity;16] thus, this stereochemistry
was assumed for compound 12c. Metal and chiral auxiliary-free
products are easily accessible in high enantiomeric purity as
indicated in Scheme 4 with the transformation of 12 b into the
1,5-dicarbonyI compound 14.[171
The absolute configuration of the newly formed stereogenic
center at the /lposition of the carbene complex was determined
by the single-crystal X-ray structure analysis of compounds
8a['*] (Fig. 1 ) and l2a.[l9IIn all other products it was assigned
by analogy.
The asymmetric induction that has been observed in all these
reactions can be explained in terms of the model shown in Figure 2. In this drawing of the most stable conformation the appropriately positioned phenyl group shields selectively the front
face of the double bond by qn-orbital overlap[*'] forcing the
nucleophile to attack preferentially on the opposite side.[*' I This
model is similar to the "n-stacking"
one previously proposed by W.
Oppolzer et a1.['*1 for cuprate
additions to enoates and the
one depicted by E. Nakamura
et aLC6]to explain the diastereoseoc-cr=c
lective syn Michael addition of enolates to Fischer vinylcarbene comco co
The net transformations deFig. 2. Model proposed to exscribed here are the synthetic
plain the asymmetric inducequivalent of Michael additions of
tlon of the Michael
alkyllithium compounds and kediscussed here
tone enolates to x,P-unsaturated aldehydes. The present carbene
route offers an attractive alternative to this otherwise generally
Exper imen tal Pro cediire
lob: To a cooled ( - 80 C ) solution o f 3 b (1.44 g, 2.68 mmol) in T H F (30 niL) was
added a 2.5 M solution of BuLi in hexane (1.15 mL. 2.8 mmol) under nitrogen and
the mixture was stirred at -80 C for 1 h and between -80 - C and room temperature for 0.5 h. After ieinoval of the solvents in vacuo :I solution of NaOMe (ca.
0.5 M ) in MeOH (20 mL) was added and the mixture &as stirred at room temperature for 3 h. MeOH was removed and the residue was purified by column chromatography (silica gel. hexane' Et,O. 4 : l ) to give 0.83 g (76%) o f 9 b . To a solution
of 9b (0.75 g. 1.86 mmol) in T H F (30 mL) was added 1 M HCI (3 mL) and the
mixtui-estirred at room temperature for 10 h. The solvent was removed in vacuo and
the residue was purificd by column chromatograph) (silica gcl. hexanc: EtfJ. 10: 1 )
to give 0.29 g ( 8 2 % ) of lob.
Received: January 31, 1994 [Z 6658 IE]
German version: h g r w . Cheni. 1994~106. 1451
[I] Recent reviews: a ) H. G . Schmali. in ('ainprdicnsirc OrKauir SInr/ic5i,s, Vol. 4
(Eds.: B. M. Trost, 1. Fleming). Pergamon. New York, 1991, p. 199: b) P.
Perlmutter. Coii/riguta Additiuii Rmctioiis in Orgunic Si.nrhe.$is,Pergamon. 0 x ford, 1992; for recent examples. see: c) K. Ruck. H. Kunz, Swt/icsi,\ 1993.
1018; d ) M . Yamaguchi, T. Shiraishi, M. Hirama. Angrir. Chrwi. 1993. 105.
1243, Aiigew. C/?en?.
h i . Ed. Engl. 1993, 32. 1 176; e) E. J. Corey. I. N. Houpis,
34. 2421; f ) A. Tatsukawa. M . Dan. M. Ohbatake. K.
Tctrulmlron L P ~1993.
Kawatake. T. Fukata. E Wada, S. Kaiiemasa. S. Kakei,.I Org. Chcni. 1993. .V.
4221 : g) S. Hanessian. A. Gomtcyan. A Payne. Y. Herie, S. Beaudoin, r h i r l
1993.58. 5032.
[2] W. D. Wulff in Coi?iprr,he,,r Orgunic Si.nrhcr!.\. Vul. 5 (Eds : B. M. Trost. I
Fleming). Pergamon. New, York. 1991. p. 1065.
[3] a) C. P. Casey. W. R. Brunsvold. J Orgunonzer. Chcni. 1974, 77. 345: b) ;hid
1975, 1/12?175: c) Iiiorg. f/zmi. 1977. 16, 391.
[4] a) I;.W. Macomber. M. H. Hung. A. G. Verma. R. D. Rogers. Organonwtullies 1988, 7,2072: b) D. \V. Macomber, P. Madhukar. R D. Rogers, ihrd. 1991.
/(I. 2121. c) S. Aoki. T Fujimura, E Nakamura. 1 A m . Clicni. So<. 1992, 1!4.
2985; conjugate addition of alkyl radicals (formal Michael reactions): d ) C A.
Merlic. D. Xu. ihirl. 1991. 113, 9855;e) C. A. Merlic. D . Xu. M. C. Nguyen. V.
Truong. Tc,rru/idmii LPII.1993. 34. 227.
[5] Carbon nucleophiles: a) S. L. B. Wang. W. D. Wulff. J A m . Chem. Soc. 1990.
f 12, 4550, b) H. Fischer, T. Meisner. J. Hofmann. Chon. Brr. 1990. 123. 1799.
Nitrogen nucleophiles: c) F Stein. M. Duetsch. R. Lackmann. M. Noltemeyer,
A. de Meijere. A n g m . Clieni. 1991. 103, 1669. .4n,yeir. Chcni./ n f . Ed. E q i .
1991. 30. 1658; d) M . Duetsch. F. Stein. R . Lackmann. E. Pohl. R. Hei-hstInner, A. de Meijere, Ciieni. Bcr. 1992. 125. 2051; e) R. Pipoh. R. van Eldik.
1993. 12. 2668 Oxygen nucleophiles- f ) F. Camps. A. Lleharia. J. M. Moreto. S. Ricart. J. M. Viiias, J. Ros. R. Ki1ie7. ./. Organowr C / w n
1991. 401. C17: g) R. Aumann. Choii. Brr. 1992. 125. 2773.
[6] E. Nakamura. K . Taiiaka. T. Fujimura. S. Aoki, P. G. Williard. .I Ani (%en?.
Soc. 1993. 115, 9015.
[7] B. A. Anderson. W. D . Wulff. A. Rahm, J. ,4im Chrii?. SOC.1993. ff5. 4602.
[8] J. Barluenga. J. M. Montsei-rat. J Flhrez. 1 C/ZPIII.
&I(. C'licn?.Cotninliti. 1993.
[9] First reported a s chiral auxiliar) : E. J. Corey. H. E. Ensley. 1 Air? C/irrii. Soc.
1975, 97. 6908.
[lo] E. 0 Fixher. A. Maasbd, C/wii. Bcr. 1967. 100. 2445.
1111 a ) E. 0.
Fischer. T.Selmayr. F. R Kreissl. Chem. Brr. 1977. 1111,2947;b) M . F.
Semmelhack. J. J. Bozell, Terruhrdim Lerr. 1982. 23. 2931; c) B. C. Soderherg.
L. S. Hegedus, M. A. Sierra. J An?. Chwi. Soc.. 1990. 112, 4364.
[I21 R Aumann. H. Heineii. Uzeiii. Ber. 1987, 120. 537.
[I31 J. Barluenga, J. Florez. M. Yus. J Chem. SIC.
Pwkiii Trunr. I 1983, 3019.
[14] Other approaches to the tricyclic compounds are currently being investigated
in our laboratory.
[15] This tramformation is more frequently carried out with pyridine: E. 0.
Fischer. D. Plahrt. C/i(mi.Bcr. 1974. 107. 3326. We first used sodium methoxide
with the aim of inducing the intramolecular alkoxide exchange reaction of
compouiid Sb: C. A. Merlic, D . Xu, B. G. Gladstone, J Org. Chcii7. 1993. 58.
[I61 H 0. House. M. Gall. H. D . Olmstead. J Org Clinn. 1971. 36. 2361.
[17] All new compounds were characterized spectroscopically ('H. " C NMR. IR)
and by mass spectrometry
1181 Crystal data for 8 a : C,,H,,CrO,, M , = 582 63. orthorhomhic. space group
P 2 , 2 , 2 , . u = l O 8 7 5 ( 3 ) . h=14.134(4). c=20.91(1).&. V = 3214.[2)A3. Z =
4. { J ~ =~ 1 ,. 2~0 g~ c m - ' . F(000)=1232, r . ( M o , , ) = 0 . 7 1 0 7 3 ~ . / 1 = 3 . 8 c m - ' ,
T = 293 K Yellow crystal (0.20 x 0.10 x 0.10 mm) obtained from a hexane solution at - 30 C. Enraf-Nonius CAD4 diffractometer. w 2 H scan technique.
Of 6609 reflections measured (0 < H < 2 5 ) . 5637 used in refinement. The
structure was solved by Patterson methods with the program SHELXS86 [24]
and expanded by DIRDJF[25]. An absoi-ption correctioii was applied by using
, I ,
VCH ~~rlri~.\ge.rc//.rC/i[i/r
rnhH. D-69451 Weinheini, 1994
DIFABS [26]. Full-matrix least-squares refinement on IF[' was made with
SHELXL93 [27]. All non-hydrogen atoms were anisotropically refined. Most
hydrogen atoms were located by differeiicc Fourier synthesis. Final conventional K = 0.048 (for 1550 Fo > 4 u(F,)) and wR2 = 0.131 (for all reflections
(5637)) 11' =l.O:[uz[F~)
+ (0.0625P)2]where P = (Max(F:, 0) + 2 F:)#3. The
absolute configuration was checked with the BIJVOET Program [28] and _en\e
B = 0.46(7) for the 100 strongest Friedel pairs. (Flack 1 parameter [29]
0.0076(402)). Total number of parameters 394 Residual electron density less
than 0.18 e k 3 The plot in Figure 1 was made by EUCLID package [30].
Further details of the crystal structure determination are available on request
from the Director of the Cambridge Crystallographic Data Ceiiti-e. I ? Union
Road. GB-Cambridge CB2 1EZ ( U K ) , on quoting the full journal citation.
I191 A complete description of the X-ray structure analysls and absolute configuration determination for 12 a has been deposited at the Camhridgc Crystallographic Data Centre.
1201 Evidence for n.n-attractive interactions: a) E . J. Corey, Y. Matsumurrc. Terroiierbon Ldr. 1991, 32. 6289: b) E. J. Corey. T. P. Loh. J An?. Chpni. Sol. 1991,
113. 8966; c) J. M. Hawkins. S. Loren, ihid. 1991, 113, 7794. and references
[21] A ci.suid conformation. less stable due to more steric interactions. and which
would lead to the Yame sense of asymmetric induction cannot he ruled out at
this time.
[22] a ) W. Oppolzer. H. J LDhcr. Heh. Chin7. A m i 1981. 64, 2808; b) J. d'Angelo,
J. Maddaluno. 1 hi Cheni. Soc. 1986. 108, 8112
[23] G. V. Kryshtal. V. V. Kulganek, V. E Kucherov. L. A. 'fanovskaya. Sjnrhecis
1979, 107.
1241 G. M. Sheldrick in C i ~ i , . \ r ~ ~ / / ~ )Conywiiig
~ r u / ~ / i i ~3, SHELXS86. (Eds.: G. M.
Sheldrick. C. Kruger, R. Goddard), Clarendon, Oxt'ord, 1985, pp. 175-189.
[25] P. T. Beurskens. G. Admiraal. G. Beurskens. W. P. Bosman, S Garcia-Granda.
R. 0 Gould. J. M. M. Sniits. C. Smykalla. The DIRL)IFprogrum.sjsi[~/i?.
E4n i d Repor1 of the Crj .sru//ogruphj~Lahorlltorv, University of Nijmegen, The
Netherlands. 1992.
[26] N. Walker. D. Stuart. Acfa C'j.s/u//ogr. Scci. A , 1983. 39. 158.
[27] G. M. Sheldrick in Cr~rru//ogrriphi(~
Coinpurrrig 6. SHELXL93 (Eds. H. D
Flack, P. Pal-kanji. K. Simon). Clarcndon. Oxford. 1993.
1281 G Beurskens. J. H. Noordik, P T. Beurskens. Crvsr. Srrucr. C~unnnun.1980, Y.
[29] H. D. Flack. Acfu ('ri..s/rrNo~r.See!. A . 1983. 39. 876
[30] A. L. Spek in Con?purutionu/ Cr~.stu/lngruph,v.Thr EUCLID Puckage (Ed.: D.
Sayre), Clarendon. Oxford. 1982. p. 528.
New Cyclic Derivatives of 3'-Amino-3'-deoxyadenosine-5'-diphosphate, -triphosphate, and
Morr" and Victor Wray
Dedicated to Professor Fritz Wogner
on the o(cavot7 OJ his 65th birthdo)
Whereas a number of chemical syntheses of 3'-amino-3'-deoxyadenosine (3'-AdA) (1) have been described,"] we have been engaged for a long time in its preparation by fermentation of
Hc.lminthosporium sp. 21 5.['] Compound 1, the basic component
of the antibiotic nucleoside p u r ~ m y c i n , ' ~has
] also been modified by us in many ways. Thus 1 was phosphorylated to 3'-AdA5'monophosphate (9), which in turn was cyclized with dicyclohexylcarbodiimide (DCC) or water-soluble carbodiimide (1 -ethyl3-(3-dimethylaminopropyl)carbodiimidehydrochloride, EDC)
to yield the CAMP-analogue 3'-AdA-3',5'-cyclophosphate(1 2)
(3'-NH-cAMP) .[4, 51 This was used for inhibition studies with
CAMP-dependent protein kinase.I6I A further derivative of 1 ,
3'-AdA-5'-triphosphate (7) (3'-NH,-ATP), proved to be of bio-
Dr. M. Morr. Di-. V. Wi-iiy
G B F - Gesellschaft fur Biotechnologische Forschung mbH
Mascheroder Weg 1. D-38124 Brdunschweig (FRG)
Telefax: Int. code + (531)6181-302
We are grateful to Mrs. D. Doring. Technical University of Brdunschweig. for
recording the FAB mass spectra.
f ~ 5 7 ~ 1 - U K 3 3 ~ 9 4 ~ 1 3 / 3 -.Y1 3I/I.~JO+
Angrit,. Chrni Inr. E d Engl. 1994, 33, Yo. I 3
Без категории
Размер файла
382 Кб
chiral, asymmetric, michael, additional, unsaturated, complexes, alkoxycarbene, chromium
Пожаловаться на содержимое документа