Asymmetric alkylation of nitroalkanes

Article abstract of DOI:10.1002/1521-3773(20000901)39:17<3122::AID-ANIE3122>3.0.CO;2-8

Cyclic meso-2-ene-1,4-diol diesters undergo desymmetrization and cycloalkenyl esters undergo dynamic kinetic asymmetric transformations with excellent enantioselectivity when nitromethane and 2-nitropropane are used in the reaction (see scheme). A short s

Full text of DOI:10.1002/1521-3773(20000901)39:17<3122::AID-ANIE3122>3.0.CO;2-8

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[1] a) G. Süss-Fink, G. Meister, Adv. Organomet. Chem. 1993, 35, 41;
b) Metal Clusters in Catalysis (Ed.: B. C. Gates, L. Guzci, V. H.
Knozinger), Elsevier, Amsterdam, 1986; c) Catalysis by Di- and
Polynuclear Metal Cluster Complexes (Ed.: R. D. Adams, F. A.
Cotton), WILEY-VCH, New York, 1998; d) P. Braunstein, J. Rose
in Comprehensive OrganometallicChemistry , Vol. 10, (Eds.: E. W.
Abel, F. G. A. Stone, G. Wilkinson), 2nd ed., Pergamon, Oxford,
1995, Chapter 7, pp. 351 ± 385; e) P. Braunstein, J. Rose in Metal
Clusters in Chemistry (Eds.: P. Braunstein, L. A. Oro, P. R. Raithby),
Wiley-VCH, Weinheim, 1999, pp 616 ± 677.
[2] a) H. Suzuki, H. Omori, Y. Moro-oka, Organometallics 1988, 7, 2579;
b) H. Omori, H. Suzuki, Y. Moro-oka, Organometallics 1989, 8, 1576;
c) H. Omori, H. Suzuki, Y. Take, Y. Moro-oka, Organometallics 1989,
8, 2270; d) H. Suzuki, T. Takao, M. Tanaka, Y. Moro-oka, J. Chem.
Soc. Chem. Commun. 1992, 476; e) H. Suzuki, H. Omori, D. H. Lee, Y.
Yoshida, M. Fukushima, M. Tanaka, Y. Moro-oka, Organometallics
1994, 13, 1129; f) T. Takao, H. Suzuki, M. Tanaka, Organometallics
1994, 13, 2554; g) H. Suzuki, Y. Takaya, T. Takemori, M. Tanaka, J.
Am. Chem. Soc. 1994, 116, 10779; h) T. Takao, S. Yoshida, H. Suzuki,
M. Tanaka, Organometallics 1995, 14, 3855; i) K. Tada, M. Oishi, H.
Suzuki, M. Tanaka, Organometallics 1996, 15, 2422; j) A. Inagaki, Y.
Takaya, T. Takemori, H. Suzuki, M. Tanaka, M. Haga, J. Am. Chem.
Soc. 1997, 119, 625; k) K. Matsubara, R. Okamura, M. Tanaka, H.
Suzuki, J. Am. Chem. Soc. 1998, 120, 1108; l) K. Matsubara, A.
Inagaki, M. Tanaka, H. Suzuki, J. Am. Chem. Soc. 1999, 121, 7421;
m) A. Inagaki, T. Takemori, M. Tanaka, H. Suzuki, Angew. Chem.
2000, 112, 411; Angew. Chem. Int. Ed. 2000, 39, 404.
Chem. 1994, 473, 187; g) H. Tobita, H. Izumi, S. Ohnuki, M. C. Ellerby,
M. Kikuchi, S. Inomata, H. Ogino, J. Am. Chem. Soc. 1995, 117, 7013;
h) R. S. Simons, C. A. Tessier, Acta Crystallogr. Sect. C 1995, 51, 1997;
i) R. S. Simons, C. A. Tessier, Organometallics 1996, 15, 2604; j) P.
Braunstein, M. Knorr, C. Stern, Coord. Chem. Rev. 1998, 178 ± 180,
903 ± 965.
[9] Diffraction measurement was made on a RAXIS-2 imaging plate area
detector at À708C. In the reduction of the data, Lorentz and
polarization corrections were applied. The structure was solved by
the Patterson method (DIRDIF92, PATTY). All non-hydrogen atoms
were refined anisotropically, and all hydrogen atoms were refined
isotropically. Crystal data for 6: monoclinic, C2/c, a ˆ 18.528(3), b ˆ
11.429(2), c ˆ 19.22(1) Š, b ˆ 112.26(2)8, Vˆ 3767(2) Š3, Z ˆ 4,
1calcd ˆ 1.330 gcmÀ1; 4875 reflections (58 ꢀ 2q ꢀ 608), 4044 observed
[5b]
with F > 3s(F), 324 parameters; R ˆ 0.036, Rw ˆ 0.037.
[10] For cyclopentadienyliron complexes, see: a) H. R. Allcock, P. P.
Greigger, L. J. Wagner, M. Y. Bernheim, Inorg. Chem. 1981, 20, 716;
b) B. Deppisch, S. Schafer, Acta Crystallogr. Sect. C 1983, 39, 97 5;
c) H. G. Raubenheimer, F. Scott, S. Cronje, P. H. Van Rooyan, J.
Chem. Soc. Dalton Trans. 1992, 1859; d) C. Klasen, G. Effinger, S.
Schmidt, I.-P. Lorenz, Z. Naturforsch. B 1993, 48, 705; e) I.-P. Lorenz,
W. Pohl, K. Polborn, Chem. Ber. 1996, 129, 11.
[11] The free activation energy for this dynamic process was estimated as
DG= (158C) ˆ 13.5 kcalmolÀ1. This value is comparable to those for
site exchange of hydrides in the diruthenium bis-m-silylene com-
plex [{(h5-C5Me5)Ru(m-H)}2{m-SiPh(OH)}(m-SiPh2)] (DG= (08C) ˆ
12.6 kcalmolÀ1). T. Takao, S. Yoshida, H. Suzuki, unpublished results.
[3] K. Jonas, P. Klusmann, R. Goddard, Z. Naturforsch. B 1995, 50, 394.
[4] R. H. Crabtree, Angew. Chem. 1993, 105, 828; Angew. Chem. Int. Ed.
Engl. 1993, 32, 789, and references therein.
[5] a) Diffraction measurement was made on an AFC-7R four-circle
diffractometer equipped with graphite-monochromated MoKa radia-
tion at À1808C. The compound crystallized in the space group P2/c
with a ˆ 9.409(7), b ˆ 8.539(3), c ˆ 12.565(6) Š, b ˆ 104.64(4)8, Vˆ
976.8(8) Š3, Z ˆ 2, 1calcd ˆ 1.313 gcmÀ1
. A total of 2396 unique
Asymmetric Alkylation of Nitroalkanes**
reflections was recorded in the range 68 ꢀ 2q ꢀ 558, of which 1968
were used (F > 3s(F)) for solution and refinement. In the reduction of
the data, Lorentz/polarization corrections and empirical absorption
corrections based on azimuthal scans were applied to the data. The
structure was solved by the Patterson method (DIRDIF92, PATTY),
and all hydrogen atoms were refined isotropically and all non-
hydrogen atoms were refined anisotropically by using full-matrix
least-squares techniques on F. The final structure of 4 was refined to
R ˆ 0.027, Rw ˆ 0.026, for 167parameters. b) Crystallographic data
(excluding structure factors) for the structures reported in this paper
have been deposited with the Cambridge Crystallographic Data
Centre as supplementary publication nos. CCDC-142856 (4), CCDC-
142858 (5), and CCDC-142857( 6). Copies of the data can be obtained
free of charge on application to CCDC, 12 Union Road, Cambridge
CB21EZ, UK (fax: (‡44)1223-336-033; e-mail: deposit@ccdc.cam.
ac.uk).
Barry M. Trost* and Jean-Philippe Surivet
The utility of nitro compounds as synthetic intermediates
stems from the versatility of the reactivity of the nitro group.[1]
One feature arises from the ease of formation of nitronate
anions; however, their low reactivity generally limits the
reactions they undergo to carbonyl and conjugate addition.[2]
Alkylations do not normally proceed well. On the other hand,
Pd-catalyzed allylic alkylations have had some success.[3] This
success stimulates the search for an asymmetric allylic
alkylation (AAA) which has had good results in only one
case (the 1,3-diphenylallyl system) and when nitromethane
was used as solvent.[4] We here report that the Pd-catalyzed
AAA reaction[5] of nitroalkanes with cyclic allyl esters can
proceed in high yields and enantioselectivities and provide a
short asymmetric synthesis of a carbanucleoside.
[6] N. Koga, K. Morokuma, J. Mol. Struct. (THEOCHEM) 1993, 300, 181.
[7] Diffraction measurement was made on an AFC-7R four-circle
diffractometer at À508C. In the reduction of the data, Lorentz,
polarization, and empirical absorption corrections based on azimuthal
scans were applied to the data. The structure was solved by the
Patterson method (DIRDIF92, PATTY). All non-hydrogen atoms
Our initial studies focused on desymmetrization of meso
diesters [Eq. (1)].[6] Our earlier results suggested the diben-
À
were refined anisotropically, and hydrogen atoms except for Fe H
À
and Si C6H5 hydrogen atoms (refined isotropically) were fixed at
the calculated positions. Crystal data for 5: monoclinic, P21/a,
a ˆ 15.741(3), b ˆ 16.938(2), c ˆ 11.432(2) Š, b ˆ 102.00(1)8, Vˆ
2981.3(7) Š3, Z ˆ 4, 1calcd ˆ 1.262 gcmÀ1; 8970 reflections (68 ꢀ 2q ꢀ
558), 6318 observed with F > 3s(F), 364 parameters; R ˆ 0.041, Rw ˆ
0.044.[5b]
[*] Prof. B. M. Trost, Dr. J.-P. Surivet
Department of Chemistry
Stanford University
Stanford, CA 94305-5080 (USA)
Fax : (‡1)650-725-0002
[8] a) H. Tobita, Y. Kawano, M. Shimoi, H. Ogino, Chem. Lett. 1987, 2247;
b) S. G. Anema, G. C. Barris, K. M. Mackay, B. K. Nicholson, J.
Organomet. Chem. 1988, 350, 207; c) S. G. Anema, K. M. Mackay,
B. K. Nicholson, M. V. Tiel, Organometallics 1990, 9, 2436; d) N. I.
Kirillova, A. I. Gusev, O. N. Kalinina, O. B. Afanasova, E. A. Cherny-
shev, Metalloorg. Khim. 1991, 4, 773; e) K. Ueno, N. Hamashima, M.
Shimoi, H. Ogino, Organometallics 1991, 10, 959; f) H. Tobita, I.
Shinagawa, S. Ohnuki, M. Abe, H. Izumi, H. Ogino, J. Organomet.
E-mail: bmtrost@leland.stanford.edu
[**] We thank the National Science Foundation and the National Institutes
of Health (NIH), General Medical Sciences, for their generous
Ã
support of our programs. Rhone-Poulenc graciously provided
a
postdoctoral fellowship for J.-P. S. Mass spectra were provided by
the Mass Spectrometry Facility of the University of California, San
Francisco, supported by the NIH Division of Research Resources.
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chain has been converted to a hydroxymethyl side chain in
one step,[9] this constitutes a rapid asymmetric synthesis of
such carbanucleosides.
The success of the desymmetrization led to our investiga-
tion of the cycloalkenyl substrates [Eq. (4)].[10] For the
alkylations with nitromethane, the carbonates 10 proved
zoate 1a would be superior for enantiodiscrimination. Sur-
prisingly, using nitromethane (2a, 5 equiv) with the S,S-ligand
3 and a Pd0 complex 4 in DMSO with cesium carbonate as
base led to no reaction. Similar results were obtained with the
diacetate 1b and dicarbonate 1c. Switching the solvent to
methylene chloride (but not THF nor acetonitrile) with the
diacetate 1b led to some reaction to produce 5b[7] (18% yield)
but, gratifyingly, with excellent enantioselectivity (99%).
Remarkably, changing the base from cesium carbonate to
BSA (BSA ˆ O, N-bis-trimethylsilylacetamide) in methylene
chloride now led to smooth reaction producing 5b in 75%
yield while maintaining high ee (99%).[8] Identical results
were obtained with the dibenzoate 1a to give 5a;[7] however,
the dicarbonate led to very low conversions.
The complete reverse behavior was observed with 2-nitro-
propane (2b). Neither the dibenzoate 1a nor the diacetate 1b
reacted to any appreciable extent in methylene chloride. On
the other hand, the use of cesium carbonate in DMSO with
the diacetate 1b gave a 92% yield of 5c[7] having 95% ee.
The same trend was observed for nitromethane with the
larger ring meso diesters 6a,b. Using the optimal conditions
established for 5b [Eq. (2)], the corresponding monoalky-
lated products 7a[7] and 7b[7] were obtained in 82 ± 84% yield
with near perfect enantioselectivity (99% ee).
superior to the corresponding acetates. The conditions that
proved successful in the desymmetrization with nitromethane
also proved to be successful here. For the cyclopentenyl
system 10a, the alkylated product 11a[7] was obtained in 94%
yield (97% ee). Equally satisfactory results were obtained for
the six- (99% yield, 99% ee for 11b) and seven-membered
ring systems (94% yield, 95% ee for 11c[7]). The lactone 12
also followed the same pattern to provide, after esterification,
the nitroester 13[7] in 74% yield [99% ee; Eq. (5)].
Use of 2-nitropropane allowed use of the allyl acetates as
substrates [Eq. (6)]. The reactions performed in DMSO at
room temperature with tetra-n-butylammonium acetate (for
14b) or cesium carbonate (for 14a and 14c) as base gave
The absolute configuration is assigned by analogy.[5, 6]
Further support derives from conversion of 5b to a known
carbanucleoside intermediate 9 [Eq. (3)].[3g] A (‡) rotation is
reported for the enantiomer corresponding to the ªnormalº
enantiomeric series of the carbanucleosides, thus the (À)
rotation observed for our synthetic sample indicates the
absolute configuration as depicted. Since the nitromethyl side
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excellent results (15a[7], 74% yield, 97% ee; 15b[7], 7 9%
yield, 94% ee; 15c[7], 50% yield, 96% ee).
1987, 52, 2988; g) D. R. Deardorff, K. A. Savin, C. J. Justman, Z. E.
Karanjawala, J. E. Sheppeck, II, D. C. Hager, N. Aydin, J. Org. Chem.
1996, 61, 3616.
The absolute configuration was established by correlation
as depicted in Equation (7). Alkylation of the allyl carbonates
10a ± c using methyl nitroacetate proceeds with no added base
[4] H. Rieck, G. Helmchen, Angew. Chem. 1995, 107, 2881; Angew. Chem.
Int. Ed. Engl. 1995, 34, 2687.
[5] B. M. Trost, Acc. Chem. Res. 1996, 29, 355.
[6] B. M. Trost, D. L. Van Vranken, C. Bingel, J. Am. Chem. Soc. 1992,
114, 9327; B. M. Trost, D. E. Patterson, J. Org. Chem. 1998, 63, 1339.
[7] All new compounds have been satisfactorily characterized spectro-
scopically and their elemental composition established by high
resolution mass spectrometry or combustion analysis.
to give the desired products (16a,[7] 80%; 16b,[7], 93%; 16c,[7]
,
87%). Radical denitronation[11] gave the known cycloalkenyl
[8] The ee value was determined by GC using a chiral cyclosil B column.
[9] M. R. Peel, D. D. Stembach, M. R. Johnson, J. Org. Chem. 1991, 56,
4991.
[10] B. M. Trost, R. C. Bunt, J. Am. Chem. Soc. 1994, 116, 4089.
[11] N. Ono, H. Miyake, R. Tamura, A. Kaji, Tetrahedron Lett. 1981, 22,
1705; D. D. Tanner, E. V. Blackburn, G. E. Diaz, J. Am. Chem. Soc.
1981, 103, 1557. Also see: J. Torno, D. S. Harp, G. C. Fu, J. Org. Chem.
1998, 63, 5296; for a review, see: N. Ono, A. Kaji, Synthesis 1986, 693.
Enantiomeric Self-Recognition:
Cation-Templated Formation of Homochiral
Isoguanosine Pentamers**
acetates 17a ± c[10] thereby establishing the absolute config-
uration of 16a ± c. Alternatively, hydrolysis with concomitant
decarboxylation gave the nitroalkenes (11a, 64% yield, 85%
ee; 11b, 65% yield, 95% ee; 11c, 72% yield, >99% ee)
thereby establishing their absolute configurations as depicted.
The utility of nitroalkanes as building blocks makes a
significant step forward as a result of the ability to effect AAA
reactions using cyclic allyl esters. It is clear that the nitro-
alkane significantly influences the catalyst. The significantly
different reactivity between nitromethane and 2-nitropropane
highlight this fact. A possible explanation suggests that the
nitronate derived from nitromethane may serve as a com-
petitive ligand to palladium. The lack of polyalkylation of
nitromethane is noteworthy especially considering that the
higher nitroalkanes are better nucleophiles and the reported
significance of this problem in another system.[4] The current
method provides a practical approach to these chiral nitro-
alkanes that enhances their utility as useful building blocks.
Xiaodong Shi, James C. Fettinger, Mangmang Cai, and
Jeffery T. Davis*
Stereochemical information embedded within the building
blocks of biopolymers is often translated into higher organ-
ization. Both the protein a-helix and the DNA duplex,
structures that require homochiral chains, rely on such a
hierarchy.[1] To illustrate the impact of stereochemistry in
controlling the structure of noncovalent aggregates, we
describe the enantiomeric self-recognition of the racemic 5'-
tert-butyldimethylsilyl-2'-3'-di-O-isopropylidene-substituted
isoguanosine, isoG 1, to give homochiral, hydrogen-bonded
pentamers.
Self-recognition is a process whereby a compound selec-
tively associates with its own kind. Self-recognition relies on:
1) reversible processes[2] and 2) a subunitꢁs ªpre-dispositionº[3]
towards self-assembly. Stereochemistry can be crucial for self-
recognition. Enantiomeric self-recognition in supramolecular
systems has been achieved using metal ion coordination[4, 5] or
hydrogen bonds.[6±8]
Received: March 28, 2000 [Z14909]
[1] R. G. Coombes in Comprehensive OrganicChemistry, Vol. 2 (Eds.:
D. H. R. Barton, W. D. Ollis, I. O. Sutherland), Pergamon Press,
Oxford, 1979, pp. 303 ± 382; D. Seebach, E. W. Colvin, F. Lehr, T.
Weller, Chimia 1979, 33, 1; G. Rosini, R. Ballini, Synthesis 1988, 833;
The Chemistry of Amino, Nitroso, Nitro and Related Groups (Ed.: S.
Patai), Wiley, Chichester, 1996.
[2] For asymmetric additions, see: H. Sasai, N. Itoh, T. Suzuki, M.
Shibasaki, Tetrahedron Lett. 1993, 34, 855; E. M. Vogel, H. Gröger, M.
Shibasaki, Angew. Chem. 1999, 111, 1671; Angew. Chem. Int. Ed. 1999,
38, 1570; K. Funabashi, Y. Saida, M. Kanai, T. Arai, H. Sasai, M.
[*] Prof. J. T. Davis, X. Shi, Dr. J. C. Fettinger, M. Cai
Department of Chemistry and Biochemistry
University of Maryland
College Park, MD 20742 (USA)
Fax : (‡1)301-314-9121
E-mail: jd140@umail.umd.edu
Â
Â
Shibasaki, Tetrahedron Lett. 1998, 39, 7557; P. Bako, K. Vizvardi, Z.
Bajor, L. Toke, Chem. Commun. 1998, 1193.
[**] This research was sponsored by the Separations and Analysis
Program, Chemical Sciences Division, Office of Basic Energy
Sciences, U.S. Department of Energy. J.D. thanks the Dreyfus
[3] a) P. Aleksandrowicz, H. Piotrowska, W. Sas, Tetrahedron 1982, 38,
1321; b) P. A. Wade, S. D. Morro, S. A. Hardinger, J. Org. Chem. 1982,
Foundation for
a Teacher-Scholar Award. We thank Professors
Ã
47, 365; c) D. Ferroud, J. P. Genet, J. Muzart, Tetrahedron Lett. 1984,
Giovanni Gottarelli and Steve Rokita for helpful discussions.
25, 4379; d) V. I. Ognyanov, M. Hesse, Synthesis 1985, 645; e) J. P.
Ã
Supporting information for this article is available on the WWW under
http://www.wiley-vch.de/home/angewandte/ or from the author.
Genet, S. Grisoni, Tetrahedron Lett. 1986, 27, 4165; f) J. Tsuji, T.
Yamada, I. Minami, M. Yuhara, M. Nisar, I. Shimizu, J. Org. Chem.
3124
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