Effective, selective hydroalkoxylation/cyclization of alkynyl and allenyl alcohols mediated by lanthanide catalysts

Article abstract of DOI:10.1021/ja071707p

Catalytic hydroalkoxylation/cyclization reactions of alkynyl and allenyl alcohols are efficiently mediated by homoleptic lanthanide amides Ln[N(SiMe₃)₂]₃ (Ln = La, Nd, Sm, Y, and Lu). Conversions are found to be highly selective with products distinctly different from those produced by conventional transition metal catalysts. Turnover frequencies as high as 18.0 h^-1 at 60 °C are observed. Kinetic studies indicate that these transformations are zero-order in [substrate] and first-order in [catalyst]. Catalytic cycles are proposed in which insertion of C-C unsaturation into a Ln-O bond is turnover-limiting. Copyright

Full text of DOI:10.1021/ja071707p

Published on Web 05/17/2007
Effective, Selective Hydroalkoxylation/Cyclization of Alkynyl and Allenyl
Alcohols Mediated by Lanthanide Catalysts
Xianghua Yu, SungYong Seo, and Tobin J. Marks*
Department of Chemistry, Northwestern UniVersity, EVanston, Illinois 60208
Received March 11, 2007; E-mail: t-marks@northwestern.edu
Scheme 1. Proposed Catalytic Cycle for Lanthanide-Mediated
Hydroalkoxylation/Cyclization of Alkenyl, Allenyl, and Alkynyl
Alcohols
Nitrogen- and oxygen-containing heterocycles are important
structural components of a vast array of naturally occurring and
pharmacologically active molecules.1 The limitations of traditional
heterocycle synthetic methodologies have stimulated considerable
interest in developing of new, efficient catalytic methods for the
synthesis of heterocyclic compounds.2 Catalytic formal addition of
an X-H bond, where X ) O, N, across C-C unsaturation is in
principle an attractive, atom-economical route for the synthesis of
functionalized heterocycles.3 However, due to a number of factors,
including the relatively high bond enthalpies of most X-H σ-bonds
and the modest reactivity of electron-rich olefins with nucleophiles,
efficient catalytic intramolecular hydrofunctionalization remains a
challenge. Olefin hydroalkoxylation (HO) is an area with limited
numbers of catalysts and is relatively unexplored.3-6 Only a few
alkali and transition metal HO catalysts have been studied, with
limited reported reaction yields and scope. Organolanthanide
complexes are known to be highly active hydrofunctionalization
catalysts.7,8 Their versatility in hydroamination and hydrophosphi-
nation raises the intriguing question of whether or not these efficient
catalysts could mediate hydroalkoxylation. Bond energetic consid-
erations9 for unexplored alkene-, alkyne-, and allene-lanthanide
alkoxide cycles (Scheme 1) predict net exothermic processes for
all alcohols; however, the very large Ln-O bond enthalpy9a renders
insertive step i very endothermic for alkenyl alcohols. Here we
report the effective and selective intramolecular HO/cyclization of
alkynyl and allenyl alcohols mediated by homogeneous lanthanide
catalysts.
Table 1. Catalytic Hydroalkoxylation/Cyclization by Precatalyst
La[N(SiMe3)2]3 (5 mol %) in Benzene-d6
In the present study, homoleptic lanthanide amides, Ln-
[N(SiMe3)2]3, are found to undergo instantaneous protonolysis with
C-C unsaturated alcohols (substrates 2-7 in Table 1) at room
temperature to form the corresponding alkoxides and free HN-
(SiMe3)2. At 60 °C, substrate 2 undergoes conversion to cyclic
methylenetetrahydrofuran 8 within 5 h with 5 mol % of La-
[N(SiMe3)2]3 (1a) precatalyst. Conversion is clean and quantitative
1
as monitored by H NMR spectroscopy. The regioselective exo
hydroalkoxyl addition to the alkyne here differs markedly from that
of most transition metal catalysts with similar substrates, where
endo addition is commonly observed.3a,5
Such different regiochemistries suggest that very different
mechanisms are operative.5b A similar selectivity is observed with
Ag2CO3 as the catalyst; however, only trace amounts of product
are detected unless stoichiometric substrate/catalyst ratios are
employed.5e The 2 f 8 conversion is found to be first-order in
[catalyst] and zero-order in [substrate], similar to lanthanide-
catalyzed hydroamination/cyclization processes.7 An -OH versus
-OD labeling study (entry 2, Table 1), assayed by 1H and 2H NMR
spectroscopy, indicates that deuterium is transferred to both terminal
methylene positions (products 9 and 10). The measured 2-D
turnover frequency is only slightly smaller than that for 2 (KIE )
0.95), suggesting a nonprimary isotopic effect and consistent with
the alkyne insertion being the turnover-limiting step in the catalytic
a Yields determined by NMR integration with methyltriphenylsilane as
the internal standard.
cycle. These data are consistent with the pathway in Scheme 1,
where slow alkyne insertion is followed by rapid substrate proto-
nolysis. This scenario would then be followed by ligand substitution
by another substrate molecule. Kinetic analysis of the 2 f 8
conversion between 40 and 80 °C yields ∆Hq ) 20.2(1.0) kcal/
mol, ∆Sq ) -11.8(0.3) eu, and Ea ) 20.9(0.3) kcal/mol, with the
negative ∆Sq suggesting a rather organized transition state.7 The
formation of 10 (9/10 ratio ) 54:46) suggests that any coordination
9
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10.1021/ja071707p CCC: $37.00 © 2007 American Chemical Society

C O M M U N I C A T I O N S
of the furan oxygen to the Ln3+ ion may be weak, likely due to the
abundant concentrations of free alcohol and product furan. Other
homoleptic lanthanide amide complexes {Ln[N(SiMe3)2]3, Ln )
Nd (1b), Sm (1c), Y (1d), and Lu (1e)} similarly catalyze this
reaction, with decreasing turnover frequency accompanying declin-
ing ionic radius [Nt ) 4.2 (1b), 2.1 (1c), 0.13 (1d), and 0.20 h-1
(1e)]. This pattern parallels that of organolanthanide-catalyzed
aminoalkenehydroamination/cyclizationbutnotthatforaminoalkynes.7a
Longer chain alkynol 3 (entry 3) undergoes quantitative HO/
cyclization to methylenepyran 11 at a significantly diminished Nt,
while substituted alkynyl alcohols 4 and 5 proceed more rapidly
(entries 4 and 5), consistent with previous hydroamination/
cyclization trends.7a,f In marked contrast to 2, pent-4-en-1-ol, the
olefinic analogue of 2, undergoes negligible reaction in the presence
of 1a, even at 120 °C, in accord with bonding energetic expectations
(Scheme 1).
Supporting Information Available: Experimental details and
kinetic studies. This material is available free of charge via the Internet
at http://pubs.acs.org.
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Acknowledgment. We thank NSF (Grant CHE-04157407) for
support of this research. We also thank Mr. Holming Yuen, Mr.
Charles Weiss, Mr. Joseph Letizia, and Ms. Sharon Koh for helpful
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