Imine hydrogenation by alkylaluminum catalysts

Article abstract of DOI:10.1039/c3cc47889k

Di-isobutylaluminum hydride and tri-iso-butylaluminum (DIBAL 1, TIBAL 2) are shown to be efficient hydrogenation catalysts for a variety of imines at 100 °C and 100 atm of H₂, operating via a hydroalumination/ hydrogenolysis mechanism.

Full text of DOI:10.1039/c3cc47889k

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Imine hydrogenation by alkylaluminum catalysts†
Jillian A. Hatnean,a Jordan W. Thomson,b Preston A. Chaseb and
Cite this: Chem. Commun., 2014,
50, 301
Douglas W. Stephan*a
Received 14th October 2013,
Accepted 8th November 2013
DOI: 10.1039/c3cc47889k
www.rsc.org/chemcomm
Di-isobutylaluminum hydride and tri-iso-butylaluminum (DIBAL 1, for sterically unhindered imines, nitriles, enamines, silylenol
TIBAL 2) are shown to be efficient hydrogenation catalysts for a ethers,11 substituted olefins12 and alkynes.13 In addition, FLP
variety of imines at 100 8C and 100 atm of H2, operating via a reductions have also been shown to effect the reduction of
hydroalumination/hydrogenolysis mechanism.
aniline derivatives to the corresponding cyclohexylammonium
salts.14 Such aromatic reductions have also been extended to
The reduction of unsaturated molecules by H2 is undoubtedly the reductions of N-heterocycles.15 At the same time, the nature of
the most important and widely utilized transformation in FLP catalysts has also evolved. Erker11a,16 has developed several
industry. This process is facilitated by both homogeneous highly effective intramolecular P/B systems, while N/B systems
and heterogeneous catalysts, well established technologies. have been explored by Repo and co-workers.17 Klankermayer18
While this is generally the case for a variety of substrates, the has designed chiral boranes for stereoselective reductions
production of amines from imine reduction is of significant while Wang and coworkers12a have recently shown that
interest to the chemical industry.1 The majority of atom efficient (C6F5)2BH catalyses the reduction of olefins. This latter finding
approaches involve the use of expensive precious metals including prompts us to report the ability of readily available di- and
Ir,2 Ru,3 Rh,4 and Pd.5,6 An alternative approach exploiting tri-isobutylaluminum (DIBAL 1; TIBAL 2) to catalyse imine
more abundant, but non-precious metal complexes for the reductions. In contrast to FLP catalysts, which operate via
catalytic hydrogenation of imines with H2 has garnered some heterolytic cleavage of hydrogen, the Al-catalyzed reactions are
recent attention. Cantat et al. reported the use of NHC adducts shown to proceed via a mechanism involving hydroalumination
of Zn salts to catalytically deoxygenate reactions of CO2 with of the imine double bond and hydrogenolysis of the resulting
methylanilines.7 while Blechert and Roesky et al. exploited Al–N bond.
ZnCp*2 and Zn2Cp*2 in catalytic hydroamination reactions.8
The treatment of imine, RNQC(R0)R00, with catalytic amounts
Beller et al. reported the first example of imine hydrogenation of either 1 (5 mol%) or 2 (10 mol%) under H2 (102 atm) in toluene
catalyzed by Zn(OTf)2,9 while we recently have used ZnCp*2 in at 100 1C for 24 h resulted in reduction to the corresponding
the presence of N-heterocyclic carbenes (NHCs) to effect the amine (Table 1). Both catalysts were effective in reducing imines
catalytic hydrogenation of imines with H2.10
with small donating groups on N (R = Me or SiMe3) in near
A further alternative to precious metals that has garnered quantitative yields. These substrates typically are not hydro-
attention in the last few years have been the use of ‘‘frustrated genated by FLP catalysts due to their ability to form strong
Lewis pairs’’ (FLPs) as metal-free hydrogenation catalysts.11 adducts with boron. In general, substrates bearing bulky NtBu
While this class of catalysts was initially shown to be efficient groups or electron withdrawing substituents were reduced in poor
for bulky imine and nitrile reduction, this concept has been yield, although the imines tBuNQCHPh and tBuNQCH( p-tBuPh)
applied to a broadening range of substrates, effecting reductions were reduced in up to 79–100% yield. The quantitative reduction
of a ketamine, (2,6-Me2Ph)NQC(Me)Ph by 1 affords a racemic
mixture of the chiral amine product. Trials to use catalysts 1 and 2
a Department of Chemistry, University of Toronto, 80 St. George St., Toronto,
to hydrogenate enamines or indolines failed, again in contrast to
FLP catalysts.11
Ontario, Canada M5S 3H6. E-mail: dstephan@chem.utoronto.ca
b GreenCentre of Canada, 945 Princess Kingston, Ontario, Canada K7L 5L9
Efforts to probe the mechanism of action prompted investigation
† Electronic supplementary information (ESI) available: Synthetic, spectroscopic
of stoichiometric combinations of these aluminium reagents with
imine substrates. Reaction of 1 with the imine, PhNQCH( p-BrC6H4),
and crystallographic data are deposited. CCDC 966185. For ESI and crystallo-
graphic data in CIF or other electronic format see DOI: 10.1039/c3cc47889k
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Table 1 Hydrogenation by alkylaluminum catalysts
Conversiona (%)
Substrate
Product
1
2
MeNQCHPh
(Me3Si)NQCHPh
PhNQCHPh
PhNQCH( p-BrPh)
tBuNQCH( p-tBuPh)
(Ph2CH)NQCHPh
MeNHCH2Ph
(Me3Si)NHCH2Ph
PhNHCH2Ph
PhNHCH2( p-BrPh)
tBuNHCH2( p-tBuPh)
(Ph2CH)NHCH2Ph
98
96
100 (95)
100b
100 (87) 86
86 96
99 (97) 99 (94)
36 100 (97)
(2,6-Me2Ph)NQC(Me)Ph (2,6-Me2Ph)NHCH(Me)Ph 100 (94) 30
tBuNQCHPh
BnNQCHPh
tBuNHCH2Ph
BnNHCH2Ph
79
43
60
56
tBuNQCH( p-NMe2)
tBuNQCH(m-BrPh)
tBuNQCH( p-BrPh)
(PhO2S)NQCHPh
(p-ClPh)NQCHPh
tBuNQCH(m-OMePh)
tBuNHCH2( p-NMe2)
tBuNHCH2(m-BrPh)
tBuNHCH2( p-BrPh)
(PhO2S)NHCH2Ph
( p-ClPh)NHCH2Ph
tBuNHCH2(m-OMePh)
48c
29c
31c
25c
15c
16c
33c
36c
25c
20c
38c
0c
Scheme 1 Proposed hydrogenation pathway of imines by 1 and 2.
a
b
Yield based on 1H NMR data, isolated yields in parentheses. N–Si
This is also reflected in the Al–N–Al and N–Al–N angles of
91.56(7)1 and 88.44(7)1, respectively.
c
bond hydrolysed upon aqueous workup. Reaction time: 48 h.
It is reasonable to propose that the mechanism of hydro-
genation of imines proceeds via initial hydroalumination of
imine as evidenced by the isolation of 3 and 4. The subsequent
reaction of the Al-amide with H2 proceeds to regenerate the
Al–H bond, liberating the amine. This hydrogenolysis of the
Al–N bond is thought to be facilitated by elevated temperatures
by effecting dissociation of the Al-amide dimer. The mono-
meric form can then interact with H2 affording the transient
formation of the amine–alane adduct. Thermal dissociation
liberates 1 and frees the product amine. In support of this view,
reaction of 3 with D2 generated PhNDCH2(p-BrBn) as evidenced
by 1H and 2D NMR spectra (see ESI†). Interestingly, on prolonged
standing under D2 for 1 week, scrambling of the D over the N
and alpha-C sites of the amine is observed, suggesting that
hydrogen transfer steps are reversible (see ESI,† Scheme 1).
Compound 2 is thought to as a precatalyst with the thermal
generation of 1 via loss of isobutene and subsequently proceeding
in the mechanism described for 1.
Fig. 1 POV-ray drawing of 3 (C, black; N, blue; Al, aquamarine; Br, brown).
H atoms have been omitted for clarity.
This metal-free reaction pathway stands in contrast to that
of FLP catalysts, which operates via a mechanism involving
at room temperature overnight afforded colourless X-ray quality heterolytic cleavage of H2. The present mechanism of hydro-
1
crystals of 3 in 92% yield. H and 13C{1H} NMR spectroscopic alumination followed by hydrogenolysis or s-bond metathesis
data of 3 were consistent with the incorporation of the imine is analogous to that described for the hydrogenation of olefins
fragment while the broad 27Al NMR signal at 67.6 ppm suggested recently reported by Wang et al.12a It is noteworthy that the
the formulation as the dimer [iBu2AlN(Ph)CH2( p-BrC6H4)]2. In a mechanism is conceptually similar to that inferred for the
similar fashion, reaction of 1 with tBuNQCH(Ph) afforded the hydrogenation of olefins under 1000 psi H2 at 220 1C employing
isolation of a colorless oil 4 in 95% yield. On the basis of NMR data BiPr320 or superacid systems,21 and to the described process for
this species was formulated as the dimer [iBu2Al(N(tBu)Bn)]2. In the the hydrogenation of coal catalysed by BI3 or alkyl boranes
case of 3 the formulation was confirmed by X-ray crystallography under forcing conditions.22
(Fig. 1). The compound is centrosymmetric with an inversion
In conclusion, the hydrogenation of imines has been demon-
symmetry relating the two halves of the dimer. The geometry strated to proceed catalysed by the addition of di-isobutylaluminum
around the N and Al atoms is pseudo-tetrahedral. The Al–N bond hydride and tri-iso-butylaluminum at 100 1C and 100 atm of H2.
lengths of 2.047(2) Å and 2.021(2) Å are comparable to those These reactions proceed via hydroalumination followed by
reported for other Al-amides.19 This small dissymmetric in the hydrogenolysis/s-bond metathesis. This unique reactivity
Al–N distances about the planar Al2N2 core presumably reflect coupled with the ability to hydrogenate sterically unhindered
steric congestion between the amide-and Al-bound substituents. substrates complements that of FLP catalysts.
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D. W. Stephan and J. Paradies, Angew. Chem., Int. Ed., 2012, 51,
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