Angewandte
Communications
Chemie
Transfer Hydrogenative Couplings
Hot Paper
Iron-Catalyzed Regioselective Transfer Hydrogenative Couplings of
Unactivated Aldehydes with Simple Alkenes
Yan-Long Zheng+, Yan-Yao Liu+, Yi-Mei Wu, Yin-Xia Wang, Yu-Tong Lin, and Mengchun Ye*
Abstract: An FeBr3-catalyzed reductive coupling of various
aldehydes with alkenes that proceeds through a direct hydride
i
transfer pathway has been developed. With PrOH as the
hydrogen donor under mild conditions, previously challenging
coupling reactions of unactivated alkyl and aryl aldehydes with
simple alkenes, such as styrene derivatives and a-olefins,
proceeded smoothly to furnish a diverse range of functional-
ized alcohols with complete linear regioselectivity.
T
he catalytic hydrogenative or transfer hydrogenative cou-
pling of p-unsaturated reactants with carbonyl compounds
À
has recently emerged as one of the most attractive C C bond-
forming methods.[1] Unlike traditional catalytic reductive
[2]
À
C C couplings that employ alkyl metal reagents, metal
hydrides,[3] or elemental metals[4] as the reducing agents
(Scheme 1a), (transfer) hydrogenative couplings using hydro-
gen gas or hydrogen donors as greener terminal reductants
provide a much less expensive and more environmentally
À
benign C C bond-forming process without generating stoi-
chiometric amounts of metallic wastes. Following an isolated
report by Molander and Hoberg on the H2-mediated reduc-
tive cyclization of 1,5- and 1,6-dienes,[5] Krische and co-
workers pioneered the development of both hydrogenative
and transfer hydrogenative couplings of carbonyl compounds
with a variety of p-unsaturated compounds, including eno-
nes,[6a] alkynes,[6b] 1,3-dienes,[6c] enynes,[6d] allenes,[6e] and allyl
compounds.[6f] However, readily available simple alkenes,
such as styrenes and a-olefins, have always been challenging
substrates for intermolecular couplings with carbonyl com-
pounds owing to their low reactivity.[7] Although significant
progress has already been made to address this challenge, for
example, by introducing activated carbonyl compounds such
as carboxylic anhydride [Scheme 1b, Eq. (1)],[8] or by using
hydroxyoxindole as the pyruvamide precursor[9] [Eq. (2)] to
facilitate these couplings, a generally effective strategy to
achieve regioselective (transfer) hydrogenative couplings of
simple alkenes with abundant and accessible carbonyl com-
pounds such as aryl and alkyl aldehydes remains elusive.
Scheme 1. Catalytic intermolecular reductive couplings of p-unsatu-
rated reactants with carbonyl compounds.
On the other hand, catalysts based on noble metals such as
Rh, Ir, or Ru dominate these (transfer) hydrogenative
couplings of carbonyl compounds with various p-bonds.[1]
The replacement of these noble metals with less toxic,
inexpensive, and abundantly available metals is one of the
most important challenges in this field. A major breakthrough
was the nickel-catalyzed transfer hydrogenative coupling of
1,3-dienes with paraformaldehyde developed by Krische and
co-workers.[10] Iron as the second most abundant and gen-
erally non-toxic metal on Earth has become an increasingly
sought-after metal catalyst,[11] but iron-catalyzed (transfer)
hydrogenative couplings have not been developed thus far.
Herein, we report the first iron-catalyzed regioselective
transfer hydrogenative coupling of unactivated aldehydes
with simple alkenes, including styrene derivatives and a-
olefins, which is mediated by iPrOH [Eq. (3)].
There are two most commonly proposed pathways for
hydrogen transfer in metal-catalyzed (transfer) hydrogena-
tions of carbonyl compounds. The first one involves the initial
formation of a metal–hydride species and subsequent hydro-
gen transfer to the unsaturated bond.[12] The second one has
been proposed for Meerwein–Ponndorf–Verley (MPV) reac-
tions[13a] and alcohol dehydrogenase processes, which do not
[*] Y.-L. Zheng,[+] Y.-Y. Liu,[+] Y.-M. Wu, Y.-X. Wang, Y.-T. Lin, Prof. Dr. M. Ye
State Key Laboratory and Institute of Elemento-Organic Chemistry
Nankai University, Tianjin 300071 (China)
E-mail: mcye@nankai.edu.cn
Prof. Dr. M. Ye
Collaborative Innovation Center of Chemical Science and
Engineering (Tianjin), Tianjin 300071 (China)
[13b]
À
involve M H species;
direct hydride transfer from the
H donor to the unsaturated bond catalyzed by various non-
noble metal complexes is thus observed.[14] Currently, almost
all (transfer) hydrogenative couplings of carbonyl compounds
with p-unsaturated reactants have been developed on the
[+] These authors contributed equally to this work.
Supporting information for this article can be found under:
Angew. Chem. Int. Ed. 2016, 55, 6315 –6318
ꢀ 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
6315