Selective reductions with stable indium trihydride reagents

Article abstract of DOI:10.1016/S0040-4039(00)01299-5

The carbene and tertiary phosphine adducts of indane, [InH₃{CN(Mes)C₂H₂N(Mes)}] and [InH₃{P(C₆H₁₁)₃}] (Mes = 2,4,6-trimethylphenyl), have been used to reduce unsaturated organic functionalities. The success and selectivity of these reductions relative to those carried out with lighter group 13 hydride complexes is discussed. (C) 2000 Elsevier Science Ltd.

Full text of DOI:10.1016/S0040-4039(00)01299-5

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 41 (2000) 7567–7570
Selective reductions with stable indium trihydride reagents
Colin D. Abernethy, Marcus L. Cole, Aaron J. Davies and Cameron Jones*
Department of Chemistry, Cardiff University, PO Box 912, Park Place, Cardiff CF10 3TB, UK
Received 5 June 2000; accepted 28 July 2000
Abstract
The carbene and tertiary phosphine adducts of indane, [InH3{CN(Mes)C2H2N(Mes)}] and
[InH3{P(C6H11)3}] (Mes=2,4,6-trimethylphenyl), have been used to reduce unsaturated organic function-
alities. The success and selectivity of these reductions relative to those carried out with lighter group 13
hydride complexes is discussed. © 2000 Elsevier Science Ltd. All rights reserved.
Keywords: carbene; indium hydride; phosphine; selective reduction.
Boro- and alumino-hydride reagents have been exhaustively utilised in organic synthesis and
a large number of fundamental advances have been made in examining the selectivity of these
toward the hydrometallation of functional groups.1 The use of hydride complexes of the heavier
group 13 elements in organic synthesis has not been equally developed. This situation has arisen
from the increasing frailty of the metalꢀhydrogen bond as the group is descended, which has
resulted in a paucity of species available for study. Despite this, some gallium hydride
complexes, e.g. [GaH3{P(C6H11)3}], have been applied to the reduction of organic carbonyl
containing functionalities.2 Moreover, in recent years several indium hydride species have
displayed selectivity in the reduction of a variety of bi- and poly-functional compounds.3
However, the indium hydride reagents that have been studied are poorly characterised, difficult
to handle and most are thermally unstable and air-sensitive.
We have recently synthesised the first indium trihydride species,4,5 for example
[InH3{P(C6H11)3}] 1 and [InH3{CN(Mes)C2H2N(Mes)}] 2, both of which have been crystallo-
graphically characterised. The air and room temperature stability of 1 and 2 has prompted us
to apply these complexes to organic synthesis. This is of interest as indium has an electronega-
tivity between that of aluminium and gallium. Therefore it might be expected that the InꢀH
bond should have a polarity between that of the analogous AlꢀH and GaꢀH bonds. Conse-
quently, there should be a degree of chemoselectivity in the reduction of organic functionalities
,
using indium hydride reagents. In addition indium has a greater covalent radius (1.5 A) than
* Corresponding author. Tel: +44-(0)29-20874060; fax: +44-(0)29-20874030; e-mail: jonesca6@cardiff.ac.uk
0040-4039/00/$ - see front matter © 2000 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(00)01299-5

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,
either aluminium or gallium (1.25 A) which means that indane complexes, like alane but unlike
gallane complexes, should prefer to participate in hypervalent (five or six coordinate) bonding.
This preference for higher co-ordination numbers may give rise to a high degree of diastereo-
selectivity in the reduction of bifunctional substrates. In this report we compare the diastereo-,
chemo- and regioselectivity of reductions utilising 1 and 2 relative to similar reductions involving
alane and gallane reagents.
The Lewis-base adducts 1 and 2 can be readily prepared in high yield via the ligand
displacement of NMe3 from [InH3(NMe3)] or elimination of LiH from LiInH4, respectively.5
Reductions were performed under an inert atmosphere with equimolar proportions of reductant
to substrate (except where indicated) in anhydrous toluene with warming from −78°C to room
temperature and stirring overnight (ca. 15 h) before quenching with dilute acid. Product ratios
1
were determined by H NMR and in the case of liquid products, GCMS analyses. The results
are summarised in Table 1. The substrates studied are those commonly used to evaluate
reducing agents.6
Reductions of simple ketones such as acetophenone (I) were shown to go to completion.
Activated ketones such as benzoin, benzil and benzoin methyl ether (II–IV) were also reduced
in high yield with excellent diastereoselectivity. This is akin to the unstable indium hydride
and [InHCl2(THF)],3c although 1 does appear to effect substantially better
3a,b
complexes LiInH4
yields. The diastereoselective reductions of II–IV suggest a strong chelation of the substrate to
the indium centre of the complex, which allows a directed hydride delivery leading to the
observed result. Decreasing the amount of 1 to 0.33 molar equivalents had little effect on the
diastereoselectivity of the reduction of II, although only a 74% conversion was observed.
Reductions of II and III with 2 proceeded with a similar selectivity to those with 1 but with
lower conversions, which is not surprising given the considerable steric bulk of the carbene
ligand used to stabilise 2.
The diastereoselectivity observed for reduction of 4-tert-butylcyclohexanone (V) with equi-
molar proportions of 1 or 2 resulted in a predominance of the trans alcohol, the yield of the
former reduction being quantitative. This is as per many aluminium and gallium hydride
reagents2,7 and is consistent with Cieplak’s model for stabilisation of the transition state via
antiperiplanar allyic bonds.8
The attempted reduction of ethyl-4-oxocyclohexanecarboxylate (VI) with 1 equivalent of 1
proceeded in moderate yield (60%) without reduction of the ester moiety. By contrast the
reduction of ethyl benzoate performed with [AlH3(NMe3)] provides the benzyl alcohol in 80%
yield under similar conditions.2 This intimates the milder reducing nature of indane adducts
relative to that of similar alane species as predicted on electronegativity grounds. Tricyclo-
hexylphosphine indane, 1, quantitatively reduces 2-cyclohexenone (VII) to its alcohol without
any conjugate addition. This is contrary to the reducing ability of [InHCl2(THF)] which has
been shown to effect a 1,4-reduction with the allylic carbonyl of chalcone.3c In addition, both 1
and 2 were shown to be ineffective towards the reduction of ethyl benzoate (VIII) and ethyl
cinnamate (IX), whilst LiInH4, LiPhInH3 and LiPh2InH2 are known to reduce similar esters.3a
In probing the regioselectivity of reduction with 1, 2,4%-dibromoacetophenone (X) was chosen
as a substrate due to comparative data being available on its reduction with Lewis-base adducts
of borane, alane and gallane.2 As per the debromination qualities of [InHCl2(THF)],3c 1 was
shown to reduce the ketone moiety in high yield (76%), with concomitant cleavage of the
adjacent carbonꢀbromine bond in 57% of cases. This is intermediate between the behaviour of
alane and gallane complexes, the former of which effects quantitative a CꢀBr cleavage whilst the

7569
Table 1
Reduction of organic compounds with [InH3{P(C6H11)3}], 1 (bold) and [InH3{CN(Mes)C2H2N(Mes)}], 2

7570
latter effects minimal cleavage. The corresponding borane adduct, [BH3(NMe3)], is completely
inactive towards the substrate. These differences can again be explained by the intermediate
electronegativity of indium relative to aluminium and gallium which gives rise to an intermediate
MꢀH bond polarity and therefore reactivity. This contrast is compounded by the regiochemistry
of the reduction of styrene oxide (XI) with 1. The proportion of 2-phenylethanol formed in this
reduction (44%) suggests the participation of an alkoxyindium transition state that possesses a
benzylic carbocation prior to hydride transfer. This is similar to the behaviour of quinuclidine–
alane (37% primary alcohol).2 However, in keeping with the electropositive nature of MH3
adducts, the secondary alcohol is also formed in roughly equivalent yield (56%). Tricyclo-
hexylphosphine gallane reduces styrene oxide to the secondary alcohol with >99% selectivity,
which again places the indane complex, 1, in between alane and gallane complexes in terms of
its regioselectivity2.
In summary, we have proven the utility of indium trihydride complexes as selective reducing
agents. Overall, they appear to behave in an intermediate fashion to their aluminium and
gallium trihydride analogues, which was predicted based on the physical properties of the metal
involved. We believe our success in synthesising air and room temperature stable Lewis-base
adducts of indane will lead to such complexes being added to the organic chemist’s arsenal of
selective reducing agents. The study described here is currently being extended, placing emphasis
on the isolation of intermediates, as we believe the nature of these will shed light on the
mechanisms involved. The results of these investigations will be reported in subsequent
publications.
Acknowledgements
The authors wish to thank Mr. Robert Jenkins for GCMS analyses and the Engineering and
Physical Sciences Research Council for financial support (C. D. A. and M. L. C.).
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