Samarium-promoted diastereoselective reductive coupling of optically active imines

Article abstract of DOI:10.1055/s-1999-2695

The intermolecular pinacol-like coupling of optically active imines was performed stereoselectively with metallic samarium and a catalytic amount of iodine to give chiral C₂-2,2'-ethylenediimino-diethanol derivatives.

Full text of DOI:10.1055/s-1999-2695

LETTER
537
Samarium-promoted Diastereoselective Reductive Coupling of Optically
Active Imines
Reiko Yanada,*a Nobuyuki Negoro,a Masanori Okaniwa,a Yoshihisa Miwa,a Tooru Taga,a Kazuo Yanada,b Tetsuro
Fujitab
aGraduate School of Pharmaceutical Sciences, Kyoto University, Yoshida, Sakyo-ku, Kyoto 606-8501, Japan
Fax +81 (75) 7612698
bFaculty of Pharmaceutical Sciences, Setsunan University, Nagaotoge-cho, Hirakata, Osaka 573-0101, Japan
Received 23 February 1999
Metal-promoting coupling of imines has been examined
Abstract: The intermolecular pinacol-like coupling of optically ac-
but stereoselectivity and chemical yield have not been suf-
tive imines was performed stereoselectively with metallic samarium
ficiently improved.4 Only one example of high diastereo-
and a catalytic amount of iodine to give chiral C2-2,2’-ethylenedi-
selectivity was achieved with very bulky and activated
special imines, tricarbonyl(benzaldimine)chromium com-
plex.5
imino-diethanol derivatives.
Key words: samarium, imines, reductive coupling, diastereoselec-
tive, C2-2,2’-ethylenediiminodiethanol derivatives
Samarium reagents have quite unique and useful proper-
ties such as long ion radius, high coordination number,
strong Lewis acidity, and high oxophilicity. Recently,
some examples have shown high stereoselectivity in free
radical reactions by chelation between the Sm(III) cation
and oxygen functional groups.6 Previously, we reported
diastereoselective Barbier-type allylation of optically ac-
The reductive coupling of optically active imines is a use-
ful method for the synthesis of chiral C2-1,2-ethylenedi-
amine derivatives, which are important as chiral catalysts
in stereoselective reactions1 and medicinal chemistry.2
Their preparation generally includes optical resolution.3
Figure 1
Synlett 1999, No. 5, 537–540 ISSN 0936-5214 © Thieme Stuttgart · New York

538
R. Yanada et al.
LETTER
tive imines with metallic samarium(Sm) and a catalytic Various ether-type imines(6) gave the coupling products
amount of iodine.7 The reaction suggests that both nitro- (major 8 and minor 9 and/or 10) with accompanying
gen and oxygen atoms of imine may coordinate to Sm(III) amines(11) (Table 1).9,10 The diastereoselectivity
in an intermediate of the reaction. We observed also that (8:(9+10)) was from predominantly to 80:20. The ratio of
reductive coupling products of imines were sometimes 8 increased when the bulkiness of a substituent R become
produced as by-products.
more (Ph > i-Pr > Et) (Runs 3, 1, and 2). The bulkiness of
b-substituent R’also affected the diastereoselectivity. The
selectivity of 8d (R = Me, R’= Ph) was higher than that of
8b (R = Et, R’= H) (Runs 4 and 2).
The mildness and operational simplicity of our new proto-
col with Sm encouraged us to further investigate the scope
and utility with a series of representative chiral imines.
Here we would like to report that intermolecular pinacol- Unexpectedly, unusual C2-dimer 12 was produced in 8%
like coupling of optically active imines was achieved dia- yield during the coupling reaction of imine 6g as a by-
stereoselectively with samarium and a catalytic amount of product. Its structure was confirmed by the coupling reac-
iodine to afford chiral C2-2,2’-ethylenediiminodiethanol tion of imine 6h. The compound 12 was produced in 31%
derivatives.
yield with accompanying C2-dimer 8h (Run 8). The rea-
son has not been clarified why the o-methoxy group on the
phenyl ring was removed and why the CC bond formation
occurred. To our knowledge, such a bond-formation has
no precedent in samarium chemistry.
The coupling reaction8 was affected by the structure of
substrate imines (Figure 1). Both N-benzylideneaniline(1)
and N-benzylidenebenzylamine(2) gave the coupling
products in good yield (95%) but in low diastereoselectiv-
ity (dl:meso = 1.4:1). (R)-N-Benzylidene-a-methylbenzy- The absolute configuration of 8 at the newly produced
lamine(3)9 was reacted in 95% and gave better benzylic center was R, R (S, S), if imine 6 had S (R) abso-
diastereoselectivity (dl:meso = 5.7:1) than 1 and 2. These lute configuration at the a-position of nitrogen. For exam-
results imply that the diastereoselectivity of the reaction ple, (S)-6a gave (R, R)-8a at two benzylic centers. Its
might be affected by the bulkiness at the a-position of the absolute structure was confirmed by the synthesis of 8a
nitrogen atom. Among three imines derived from L-valine via another route (eq. 1). The known C2-ester(13) was pre-
derivatives, N-benzylidene-L-valinol(4), methyl N-ben- pared from (S)-5 by Shono’s method.4c The compound 13
zylidene-L-valinate(5), and N-benzylidene-O-methyl-L- was reduced with LiAlH4 and then methylated to give 8a.
valinol(6a), ether-type 6a was the best substrate for this The X-ray crystallography of 8d further confirmed our ex-
coupling reaction. Alcohol type 4 was reduced only at the perimental rule (Fig. 2).11 It shows that 8d has (RSRRSR)
C = N double bond to give N-benzylvalinol(7) quantita- absolute configuration. These results are useful to visual-
tively. Ester-type 5 was inert under these reaction condi- ize the reaction mechanism.
tions and the starting material was recovered (90%).
Scheme 1
Synlett 1999, No. 5, 537–540 ISSN 0936-5214 © Thieme Stuttgart · New York

LETTER
Samarium-promoted Diastereoselective Reductive Coupling of Optically Active Imines
539
Figure 2
(3) (a) Saigo, K.; Kubota, N.; Takebayashi, S.; Hasegawa, M.
Bull. Chem. Soc. Jpn. 1986, 59, 931-932. (b) Corey, E. J.;
Imwinkelried, R.; Pikul, S.; Xiang, Y. B. J. Am. Chem. Soc.
1989, 111, 5493-5495.
The high stereoselectivity in the coupling of 6 is explained
by the high coordination number and Lewis acidity of sa-
marium(III) reagents and the steric interaction of R and R’
groups.12 Scheme 1 illustrates the proposed mechanism
for the coupling reaction. Imine 6a is reduced with Sm
and a catalytic amount of iodine. The nitrogen and oxygen
atom of the produced imine radical coordinate to the gen-
erated Sm(III) species.13 Among three plausible radical
intermediates(8a’, 9a’, 10a’), the steric interaction seems
minimum in 8a’ to give the main product (R, R)-8a (78%
yield).
(4) For recent reports: (a) Takaki, K.; Tsubaki, Y.; Tanaka, S.;
Beppu, F.; Fujiwara, Y. Chem. Lett. 1990, 203-204. (b)
Imamoto, T.; Nishimura, S. Chem. Lett. 1990, 1141-1142. (c)
Shono, T.; Kise, N.; Oike, H.; Yoshimoto, M.; Okazaki, E.
Tetrahedron Lett. 1992, 33, 5559-5562. (d) Shimizu, M.; Iida,
T.; Fujisawa, T. Chem. Lett. 1995, 609-610. (e) Dutta, M. P.;
Baruah, B.; Boruah, A.; Prajapati, D.; Sandhu, J. S. Synlett
1998, 857-858. (f) Alexakis, A.; Aujard, I.; Mangeney, P.
Synlett 1998, 873-874. (g) Annunziata, R.; Benaglia, M.;
Cinquini, M.; Cozzi, F.; Raimondi, L. Tetrahedron Lett. 1998,
39, 3333-3336.
(5) Taniguchi, N.; Uemura, M. Synlett 1997, 51-53.
(6) (a) Molander, G. A.; Kenny, C. Tetrahedron Lett. 1987, 28,
4367-4370. (b) Molander, G. A.; Kenny, C. J. Am. Chem. Soc.
1989, 111, 8236-8246. (c) Kan, T.; Hosokawa, S.; Nara, S.;
Oikawa, M.; Ito, S.; Matsuda, F.; Shirahama, H. J. Org. Chem.
1994, 59, 5532-5534. (d) Kawatsura, M.; Matsuda, F.;
Shirahama, H. J. Org. Chem. 1994, 59, 6900-6901.
(e) Matsuda, F. J. Synth. Org. Chem., Jpn. 1995, 53, 987-998.
(f) Molander, G. A.; Harris, C. R. Chem. Rev. 1996, 96, 307-
338. (g) Kawatsura, M.; Dekura, F.; Shirahama, H.; Matsuda,
F. Synlett 1996, 373-376. (h) Kito, M.; Sakai, T.; Haruta, N.;
Shirahama, H.; Matsuda, F. Synlett 1996, 1057-1060.
(i) Kawatsura, M.; Kishi, E.; Kito, M.; Sakai, T.; Shirahama,
H.; Matsuda, F. Synlett 1997, 479-480. (j) Renaud, P.; Gerster,
M. Angew. Chem. Int. Ed. Engl. 1998, 37, 2562-2579.
(7) Negoro, N.; Yanada, R.; Okaniwa, M.; Yanada, K.; Fujita, T.
Synlett 1998, 835-836.
In conclusion, we have achieved excellent to complete
diastereoselective intermolecular coupling reactions of
optically active imines with Sm and a catalytic amount of
iodine to give C2-2,2’-ethylenediiminodiethanol deriva-
tives. Optically active aminoalcohols have extensively
been used as catalysts in alkylation of aldehyde with
alkyllithium14 or dialkylzinc,15 reduction of ketones with
borane or borates,16 and dihydroxylation of a double bond
with osmium tetroxide.17 We are trying now to use our C2-
chiral compounds for these reactions as asymmetric
ligands.
References and Notes
(1) (a) Whitesell, J. K. Chem. Rev. 1989, 89, 1581-1590.
(b) Tomioka, K. Synthesis 1990, 541-549. (c) Noyori, R.;
Kitamura, M. Angew. Chem. Int. Ed. Engl. 1991, 30, 49-69.
(d) Kolb, H. C.; VanNieuwenhze, M. S.; Sharpless, K. B.
Chem. Rev. 1994, 94, 2483-2547. (e) Bennani, Y. L.;
Hanessian, S. Chem. Rev. 1997, 97, 3161-3195.
(2) (a) von Angerer, E.; Egginger, G.; Kranzfelder, G.;
Bernhauer, H.; Schönenberger, H. J. Med. Chem. 1982, 25,
832-837. (b) Pasini, A.; Zunino, F. Angew. Chem. Int. Ed.
Engl. 1987, 26, 615-624. (c) Reedijk, J. J. Chem. Soc., Chem.
Commun. 1996, 801-806.
(8) The general procedure is as follows. A mixture of imine (10
mmol), Sm (10 mmol), and iodine (1 mmol) in THF (8 ml)
was stirred at room temperature under argon for 2 h. The
volume of THF was very important. The minimum volume of
THF gave the maximum yield of the dimer 8 and minimum
yield of by-product amine 7. Other solvents examined did not
give the C2-coupling products. The use of SmI2 gave mainly
amine 7 because of the low concentration of SmI2 (0.1 M).
(9) Enders, D.; Reinhold, U. Tetrahedron: Asymmetry 1997, 8,
1895-1946 and references cited therein.
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R. Yanada et al.
LETTER
(10) When allyl bromide is present in the reaction system,7 the
reductive addition of allyl bromide to the imines proceeds
preferentially.
implies that the generated Sm(II) in the reaction mixture reacts
immediately with imine to generate the Sm(III) species during
the reaction and that Sm(II) remained after the imine was
consumed.
(11) Crystallographic data for 8d: C34H40N2O2, M = 508.7,
orthorhombic, space group P212121, Colorless prism,
a = 12.150(4) Å, b = 20.370(9) Å, c = 6.158(2) Å, V = 1524.1
Å3, Z = 4, and Dc = 1.1083 gcm-3. The reflection data of 1320
reflections with 0<q<60° were collected on a Rigaku AFC-5
diffractometer using monochromated CuKa radiation and w-
2q scan technique (0£h£13, 0£k£22, 0£l£6). The structure
was solved by the direct method and refined by the fullmatrix
least-squares method. The final R value was 0.047 for 1260
observed reflections (wR = 0.052, w = 1/[s2(F)+0.023F2]).
(12) Shono et al. reported as follows in Ref. (4c). 1) The
intermolecular coupling of chiral imine (5) did not give
satisfactory stereoselectivity by reduction with zinc and
methanesulfonic acid. 2) The intramolecular coupling of
diimines, in which two molecules of 5 were linked by a carbon
chain, gave good stereoselectivity. 3) The stereoselectivity
was explained by steric interaction of isopropyl groups in the
diprotonated intermediate. Shono's method is the most
practical synthesis of chiral 1,2-diarylethylenediamines.
(13) A clear yellow-green supernatant was observed during the
mild exothermic reaction. After the imine was consumed, it
turned to purple and the excess of Sm(0) remained at the
bottom. It is generally known that Sm(II) solution is purple-
blue and Sm(III) solution is yellowish. The change of the color
(14) Mukaiyama, T.; Suzuki, K. Chem. Lett. 1980, 255-256.
(15) (a) Kitamura, M.; Suga, S.; Kawai, K.; Noyori, R. J. Am.
Chem. Soc. 1986, 108, 6071-6072. (b) Soai, K.; Ookawa, A.;
Kaba, T.; Ogawa, K. J. Am. Chem. Soc. 1987, 109, 7111-7115.
(c) Soai, K.; Yokoyama, S.; Ebihara, K.; Hayasaka, T. J.
Chem. Soc., Chem Commun. 1987, 1690-1691. (d) Bolm, C.;
Zehnder, M.; Bur, D. Angew. Chem. Int. Ed. Engl. 1990, 29,
205-207. (e) Kunieda, T.; Ishizuka, T. J. Synth. Org. Chem.,
Jpn. 1997, 55, 1018-1028.
(16) (a) Corey, E. J.; Bakshi, R. K.; Shibata, S. J. Am. Chem. Soc.
1987, 109, 5551-5553. (b) Corey, E. J.; Shibata, S.; Bakshi, R.
K. J. Org. Chem. 1988, 53, 2861-2863.
(17) (a) Yamada, T.; Narasaka, K. Chem. Lett. 1986, 131-134. (b)
Tomioka, K.; Shinmi, Y.; Shiina, K.; Nakajima, M.; Koga, K.
Chem. Pharm. Bull. 1990, 38, 2133-2135. (c) Ogino, Y.;
Chen, H.; Kwong, H. -L.; Sharpless, K. B. Tetrahedron Lett.
1991, 32, 3965-3968.
Article Identifier:
1437-2096,E;1999,0,05,0537,0540,ftx,en;Y04399ST.pdf
Synlett 1999, No. 5, 537–540 ISSN 0936-5214 © Thieme Stuttgart · New York