Communication
Scheme 1. Activation of the precatalyst [RuCl2(PPh3)3] (1) through additives.
perhydride” complex [Ru(H2)H2(PPh3)3] (3) [Eq. (3), Scheme 1].
In the absence of zinc, the Ru–OH complex 4 is formed from 1
in the presence of catalytic amounts of KOH [Eq. (2),
Scheme 1]. These spectroscopic results provide a direct explan-
ation for the observed chemoselectivities. For example, the ac-
tivity of the structurally similar complex [RuHCl(PPh3)3] in the
chemoselective reduction of olefins in the presence of carbon-
yl groups has been described in the literature.[9] On the contra-
ry, complex 3 is one of the most active Ru catalysts in the re-
duction of carbonyl groups and quasi inert to olefin/alkyne re-
ductions.[10]
With these results in hand, the activation of D2O under the
established conditions was studied by the reduction of diaryl-
alkynes 5–7 and acetophenone derivatives 11–13 (Scheme 2).
By addition of CuI, the Z-bis-deuterated olefins 8–10 could be
isolated in good yields of 86% at a deuteration degree of
85%. Another 14% corresponded to the E-bis-deuterated
olefin; interestingly, the degree of deuteration on both olefinic
carbon atoms was identical at about 85%. Mixed H–D-substi-
tuted olefins were undetectable. After a longer reaction time
only E-configured olefins 8–10 could be detected; a change in
the degree of deuteration or overreduction was not observed
[reaction conditions (A), Eq. (1), Scheme 2]. Upon addition of
KOD [reaction conditions (B), Eq. (2), Scheme 2], no conversion
was observed, whereas ketones 11–13, upon addition of cata-
lytic amounts of KOD, reacted cleanly to give the correspond-
ing alcohols 14–16 [Eq. (3), Scheme 2]. The H–D exchange at
the acidic a-carbon atom occurs as a KOD-catalyzed back-
ground reaction, and the addition of [RuCl2(PPh3)3] 1 was not
necessary under these conditions. In the presence of CuI as an
additive, however, no reduction of the carbonyl group and no
deuteration at the a-carbon atom was observed. Interestingly,
under these conditions a selective deuteration of the two
ortho-carbon atoms in the aromatic moiety ketones 17–19 was
observed [Eq. (4), Scheme 2].
Scheme 2. Additive-directed chemoselective reductive deuteration of car-
bonyl compounds and alkynes. [a] 16 h reaction time.
and oxidative[13] conditions. The simple H–D exchange is for-
mally a redox-neutral transformation, which raises the question
of the necessity of zinc as a reducing agent in such processes.
To obtain a better overview of the scope of ortho-deuteration,
different catalyst-directing groups were subsequently investi-
gated with regard to their reactivity (Table 1). In fact, using cat-
alytic amounts of [RuCl2(PPh3)3] (1) and KOD in the absence of
stoichiometric amounts of zinc (conditions (C)) an efficient
ortho-selective C(sp2)–H–D exchange was possible. The use of
catalytic amounts of [RuCl2(PPh3)3] (1) and CuI (conditions (A)),
on the other hand, provided the expected deuterated aromat-
ics only when using zinc.
Depending on the additive, significant differences in the
deuteration were observed. While the ortho-deuteration of
C(sp2)ÀH bonds using catalytic amounts of KOD was highly se-
lective, catalytic depletion of CuI led both to C(sp2)ÀH- and C
(sp3)ÀH bond deuteration plus in some cases ring opening of
the directing group, for example, oxazolidines. Since C(sp3)ÀH-
deuteration of benzoic acid propylamide 33 with the addition
of both KOD and CuI led to almost identical results (entry 10,
Table 1), we assume that C(sp3)ÀH-deuteration occurs prior to
the opening of the oxazolidinone. Importantly, no dehalogena-
Carbonyl groups are able to direct the ortho-selective CÀH
activation through coordination of Ru catalysts. Since the
groundbreaking work of Murai,[11] a large number of Ru com-
plexes have been developed that enable ortho-CÀH activation
by a wide variety of directing groups under redox-neutral[7,12]
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Chem. Eur. J. 2019, 25, 1 – 6
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ꢀ 2019 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
ÝÝ These are not the final page numbers!