Coupled organolanthanide-catalyzed C-N/C-C bond formation processes. Efficient regiospecific assembly of pyrrolizidine and indolizidine skeletons in a single catalytic reaction

Full text of DOI:10.1021/ja952433l

J. Am. Chem. Soc. 1996, 118, 707-708
707
Coupled Organolanthanide-Catalyzed C-N/C-C
Table 1. Intramolecular Hydroamination/Bicyclization Results
Bond Formation Processes. Efficient Regiospecific
Assembly of Pyrrolizidine and Indolizidine
Skeletons in a Single Catalytic Reaction
Yanwu Li and Tobin J. Marks*
Department of Chemistry
Northwestern UniVersity
EVanston, Illinois 60208-3113
ReceiVed July 21, 1995
The remarkable kinetic facility with which early lanthanide-
alkyl and -heteroatom bonds undergo insertion of unactivated
1
,2
3,4
alkene and alkyne functionalities within bis(pentamethyl-
1
cyclopentadienyl)metal environments (e.g., eqs 1 and 2; Cp′
5
)
η -Me5C5; X ) alkyl, NR2, PR2) has recently been docu-
mented, as has the susceptibility of the resulting Ln-C bonds
to protonolysis.2 These results raise the interesting question
,3
of whether lanthanide-mediated C-N/C-C fusions could be
coupled in sequence to assemble, in conjunction with proto-
nolysis, complex polycyclic, heteroatom-containing skeletons
a
2 2 2 2 2
Cp′ SmCH(TMS) SiCp′′ NdCH(TMS) as
as precatalyst. b Me
c d
(
e.g., pyrrolizidine, indolizidine, and other alkaloid frame-
5,6
precatalyst. NMR and preparative scale reactions. Isolated yield.
Yield determined by H NMR and GC/MS after vacuum transfer of
the volatile products. Traces of other isomers present; see text.
works) in a single catalytic reaction. We report here the facile,
regiospecific organolanthanide-catalyzed bicyclization of ami-
nodiolefins, aminodialkynes, and aminoalkenalkynes to access
e
1
f
a variety of such architectures, as well as initial observations
regarding scope and mechanism.
(
1) Alkene insertions involving alkyls: (a) Schaverien, C. J. AdV.
7
Organomet. Chem. 1994, 36, 283-362 and references therein. (b) Jeske,
G.; Lauke, H.; Mauermann, H.; Swepston, P. N.; Schumann, H.; Marks, T.
J. J. Am. Chem. Soc. 1985, 107, 8091-8103. (c) Watson, P. L.; Parshall,
G. W. Acc. Chem. Res. 1985, 18, 51-55. (d) den Haan, K. H.; de Boer,
J. L.; Teuben, J. H.; Spek, A. L.; Kajic-Prodic, B.; Hays, G. R.; Huis, R.
Organometallics 1986, 5, 1726-1733. (e) Molander, G. A.; Hoberg, J. O.
J. Am. Chem. Soc. 1992, 114, 3123-3124. (f) Yang, X.; Seyam, A. M.;
Fu, P.-F.; Marks, T. J. Macromolecules 1994, 27, 4625-4626. (g)
Molander, G. A.; Nichols, P. J. J. Am. Chem. Soc. 1995, 117, 4415-4416.
The unsaturated difunctional amine substrates shown in Table
1
were straightforwardly synthesized, purified, and characterized
8
by standard methodologies. Reactions with precatalysts Cp′2-
1
b
5
SmCH(TMS)2 and Me2SiCp′′2NdCH(TMS)2 (Cp′′ ) η -
9
Me4C5) were carried out in C6H6/C6D6 under rigorously
anhydrous/anaerobic conditions ([catalyst] ) 7.5-15 mM;
8
(
2) Alkene insertions involving heteroatoms: (a) Giardello, M. A.;
substrate:catalyst ≈ 50:1). Isolated yields in Table 1 refer to
Conticello, V. P.; Brard, L.; Gagn e´ , M. R.; Marks, T. J. J. Am. Chem. Soc.
products isolated by distillation or column chromatography.
With the exception of entries 3 and 4 (vide infra), bicyclizations
1
994, 116, 10241-10254. (b) Giardello, M. A.; King, W. A.; Nolan, S.
P.; Porchia, M.; Sishta, C.; Marks, T. J. In Energetics of Organometallic
Species; Martinho Simoes, J. A., Ed.; Kluwer: Dordrecht, 1992; pp 35-
1
proceed with g95% regioselectivity, as ascertained by H NMR
5
1
1. (c) Gagn e´ , M. R.; Stern, C. L.; Marks, T. J. J. Am. Chem. Soc. 1992,
and GC/MS, and at the turnover frequencies (Nt) indicated.
14, 275-294. (d) Gagn e´ , M. R.; Nolan, S. P.; Marks, T. J. Organome-
Product structure and stereochemistry were established by 1-D
tallics 1990, 9, 1716-1718.
1
13
8
(
3) Alkyne insertions involving alkyls: (a) Heeres, H. J.; Teuben, J. H.
and 2-D H/ C NMR, HRMS, and other standard techniques.
Organometallics 1991, 10, 1980-1986 and references therein. (b) Heeres,
It can be seen that alkyne, alkene; alkyne, alkyne; and alkene,
alkene bicyclizations can all be effected to yield a variety of
H. J.; Meetsma, A.; Teuben, J. H.; Rogers, R. D. Organometallics 1989, 8,
2
637-2646.
5
,6
(4) Alkyne insertions involving heteroatoms: (a) Li, Y.; Fu, P.-F.; Marks,
pyrrolizidine and indolizidine skeletons. Thus, entries 1 and
T. J. Organometallics 1994, 13, 439-440. (b) Li, Y.; Marks, T. J. Abstracts
of Papers, 34th National Organic Symposium, ACS Division of Organic
Chemistry, Williamsburg, VA, June 1995; American Chemical Society:
Washington, DC, 1995; Abstract 44.
-1
2
demonstrate clean and rapid (Nt as high as 777 h at 21 °C)
sequential alkyne, alkene insertive bicyclization. That alkyne
insertion into Ln-N bonds is expected to be more rapid and
4
(
5) For some leading reviews, see: (a) Robins, D. J. Nat. Prod. Rep.
exothermic than that of olefins (which in this case would also
1
994, 11, 613-619 and references therein. (b) Michael, J. P. Nat. Prod.
yield strained three-membered rings) suggests the representative
mechanistic scenario portrayed in Scheme 1. Further evidence
for this pathway derives from entries 3 and 4, in which the
second (olefinic) insertion into the R-silylvinyl-lanthanide
Rep. 1994, 11, 639-657 and references therein. (c) Daly, J. W.; Spande,
T. F. In Alkaloids: Chemical and Biological PerspectiVes; Pelletier, S. W.,
Ed.; Wiley: New York, 1986; Vol. 4, Chapter 1. (d) Mattocks, A. R.
Chemistry and Toxicology of Pyrrolizidine Alkaloids; Academic Press:
Orlando, 1986. (e) Robins, D. J. AdV. Heterocycl. Chem. 1979, 24, 247-
1
b
linkage is arrested (slow, precedented catalytic double bond
2
91.
6) For representative synthetic approaches, see: (a) Hudlickly, T.; Reed,
(
J. W. In ComprehensiVe Organic Synthesis; Trost, B. M., Fleming, I., Eds.;
(7) Communicated in part: Li, Y., Marks, T. J. Abstracts of Papers,
209th National Meeting of the American Chemical Society, Anaheim, CA,
Spring 1995; American Chemical Society: Washington, DC, 1995;
INOR012.
(8) See supporting information for full synthetic details and characteriza-
tion data for new compounds.
Pergamon Press: Oxford, 1991; Vol. 5, pp 937-965 and references therein.
(
b) Hassner, A.; Rai, K. M. L. In ref 6a, Vol. 2, pp 557-559 and references
therein. (c) Shiosaki, K. In ref 6a, Vol. 3, pp 882-885 and references
therein. (d) Overman, L. E.; Ricca, D. J. In ref 6a, Vol. 3, pp 1040-1044
and references therein. (e) McGrane, P. L.; Livinghouse, T. J. Org. Chem.
1
992, 57, 1323-1324 and references therein. (f) Jefford, C. W.; Tang, Q.;
Zaslona, A. J. Am. Chem. Soc. 1991, 113, 3513-3518.
(9) Jeske, G.; Schock, L. E.; Mauermann, H.; Swepston, P. N.; Schumann,
H.; Marks, T. J. J. Am. Chem. Soc. 1985, 107, 8103-8110.
0
002-7863/96/1518-0707$12.00/0 © 1996 American Chemical Society

7
08 J. Am. Chem. Soc., Vol. 118, No. 3, 1996
Communications to the Editor
Scheme 1. Proposed Pathway for
Organolanthanide-Catalyzed Sequential C-N and C-C
Bond Formation
illustrates that alkene, alkyne bicyclization can be employed to
produce an exo-alkene-functionalized pyrrolizidine. In this case,
2
a,c
initial olefinic insertion into the Ln-N bond
is favored,
doubtless due to the short alkyne connecting linkage. The
stereochemistry of 16 is assigned by analogy to that of 10, by
3,4
NOE difference spectroscopy, and by the expected cis course
of the alkyne insertion process.
In regard to reaction mechanism, an H NMR kinetic analysis
1
of the Cp′2Sm-catalyzed 11 f 12 transformation indicates zero-
order behavior in [substrate] over a 20-fold concentration range
and first-order behavior in [Sm] over a 15-fold concentration
range (eq 3), implicating an intramolecular, insertive process
as the turnover-limiting step. Further support for a turnover-
1
0
ν ) k[Sm] [substrate]
(3)
limiting insertion scenario is found in the pronounced correlation
of 1 f 2 turnover frequencies (at constant [Cp′2Ln], [substrate],
3+
and temperature) with decreasing eight-coordinate Ln ionic
1
3
radius (Ln (ionic radius, Å), Nt): La (1.16), 148; Nd (1.11),
-
1
4
5; Sm (1.08), 17; Lu (0.977), <0.2 h ). Similar trends obtain
in a variety of Cp′2Ln-catalyzed processes, where the turnover-
1
b,2a,c,14
limiting step is olefin insertion.
In summary, these results demonstrate that organolanthanide
centers can mediate unusual tandem sequences of insertive C-N
and C-C bond-forming processes and that such transformations
can be readily integrated into novel and regioselective catalytic
cycles. Of note is the attraction of assembling pyrrolizidine
and indolizidine skeletons having varying degrees of unsatura-
tion, hence points for subsequent functionalization, in a single
catalytic cycle. Additional applications are currently under
investigation.
migration occurs in entry 3 instead), presumably due to a
combination of electronic10 and steric impediments. The two
products indicated each contain ∼10% of other uncyclized
double bond positional isomers. Entry 5 illustrates rapid
sequential alkyne, alkyne insertive bicyclization to introduce
two regions of heterocyclic unsaturation. The stereochemistry
of 10 is assigned from NOE difference spectroscopy. Entries
Acknowledgment. We thank the National Science Foundation for
generous support of this research under Grant CHE9104112. We thank
Professor Frank McDonald for helpful discussions.
Supporting Information Available: Details of the syntheses and
characterization data for new compounds (13 pages). This material is
contained in many libraries on microfiche, immediately follows this
article in the microfilm version of the journal, can be ordered from the
ACS, and can be downloaded from the Internet; see any current
masthead page for ordering information and Internet access instructions.
6
and 7 illustrate alkene, alkene bicyclization to yield the
11
saturated (known) pyrrolizidine 12 and indolizidine 14 (cis:
trans ) 45:55 and 85:15,12 respectively). Entry 8 further
(
10) For discussions of unusual aspects of d0 metal-R-silylvinyl
electronic structure and bonding, see: (a) Horton, A. D.; Orpen, A. G.
Organometallics 1991, 10, 3910-3918. (b) Koga, N.; Morokuma, K. J.
Am. Chem. Soc. 1988, 110, 108-112. (c) Eisch, J. J.; Piotrowski, A. M.;
Brownstein, S. K.; Gabe, E. J.; Lee, F. L. J. Am. Chem. Soc. 1985, 107,
JA952433L
7
219-7220.
(12) Stereochemistry assigned from NMR comparisons to similar
compounds: Heidt, P. C.; Bergmeier, S. C.; Pearson, W. H. Tetrahedron
Lett. 1990, 5441-5444.
(13) Shannon, R. D. Acta Crystallogr. A 1976, 32, 751-767.
(14) Fu, P.-F.; Brard, L.; Li, Y.; Marks, T. J. J. Am. Chem. Soc. 1995,
117, 7157-7168.
(11) (a) Newcomb, M.; Marquardt, D. J.; Deeb, T. M. Tetrahedron 1990,
46, 2329-2344. (b) Newcomb, M.; Deeb, T. M. J. Am. Chem. Soc. 1987,
109, 3163-3165. (c) Surzur, J.-M.; Stella, L. Tetrahedron Lett. 1974,
2191-2194. (d) Skvortsov, L. M.; Antipova, I. V. J. Org. Chem. USSR
1979, 15, 777-783.