Angewandte
Communications
Chemie
Allylic Compounds
Rhodium-Catalyzed Enantioselective Intermolecular
Hydroalkoxylation of Allenes and Alkynes with Alcohols:
Synthesis of Branched Allylic Ethers
Abstract: Regio- and enantioselective additions of alcohols to
either terminal allenes or internal alkynes provides access to
allylic ethers by using a RhI/diphenyl phosphate catalytic
system. This method provides an atom-economic way to obtain
chiral aliphatic and aryl allylic ethers in moderate to good yield
with good to excellent enantioselectivities.
A
llylic ethers are key components of bioactive molecules
and natural products and serve as versatile synthetic inter-
mediates for further construction of numerous structures[1]
through a wide variety of reactions such as [2,3] and [3,3]
sigmatropic rearrangements and olefin metathesis reactions,
among many others.[1b,2,3] Significant progress towards their
synthesis has been achieved recently by employing transition
metal catalyzed allylic substitution. In most cases, allyl
acetates[4] or carbonates[5] have been used as electrophiles.
However, recent studies show that even allylic alcohols can
serve as allyl precursors.[6] To date, premetalated alkoxides
have been used as nucleophiles along with metals to soften
the hard nucleophilic character of an alkoxide (such as tin,[4a]
boron,[7] zinc,[4b,c,5f] and copper[5a,c–e]).
Scheme 1. Intermolecular allylic hydroalkoxylation. LG=leaving group.
Following on the initial work with palladium catalysts of
Initial reactions were conducted with 3-phenylpropyl
the groups of Trost[8] and Yamamoto,[9] we recently reported allene (1a) and ethanol (2b) as model substrates. First
on a series of rhodium-catalyzed pronucleophile addition reactivity assays indicated that the presence of an acidic
reactions to allenes and alkynes, reactions that can be cocatalyst was necessary. The reaction proved to work using
regarded as atom-economic alternatives to allylic substitution
a rhodium(I)/DPEphos/diphenyl phosphate catalyst in
chemistry displaying complementary branch regioselectivity dichloromethane (DCM) at 408C for 18 hours and furnished
(Scheme 1).[10] Thus, hydroamination,[11] hydroesterifica- the desired allylic ether in 34% yield (Table 1, entry 1).[15]
tion,[12] hydroacylation,[13] and hydrothiolation[14] have been Inspired by this result, various chiral bidentate diphosphine
achieved to afford versatile enantioenriched branched allylic ligands with different backbones were subjected to this model
products. In this context, it would be highly interesting if reaction. While many standard privileged chiral ligands failed
simple and non-deprotonated alcohols could be added atom to catalyze this reaction,[16] the chiral ferrocene-type ligand L4
economically to allenes or even to alkynes, thus giving proved to be the best (entries 5 and 6). To our delight,
valuable branched allylic ether products.
switching the solvent from DCM to 1,2-dichloroethane
We herein report on the implementation of such a trans- (DCE) gave the desired allylic ether in 76% yield with
formation allowing the highly regio- and enantioselective a remarkable 92% ee (entry 6).
addition of simple and functionalized alcohols, including
With these optimized reaction conditions in hand, we first
methanol and ethanol, to terminal allenes and internal explored the scope of this reaction with regard to different
alkynes to give a wide range of valuable building blocks for alcohols and 1a as the privileged allene (Table 2). Avariety of
synthetic organic chemistry.
allylic ethers could be prepared in moderate to good yields
with excellent enantioselectivities. Not only common primary
alcohols but also alcohols possessing functional groups such as
chloro, unprotected hydroxy, TMS, and alkenyl moieties (3e–
h) behaved well in this reaction. Notably, upon employing
propane-1,3-diol as the reaction partner, only the monoally-
lated product 3 f was obtained in 71% yield with 92% ee. In
addition to this, secondary alcohols were also successfully
allylated to furnish the corresponding products (3k,l) with
high enantioselectivities, but with slightly lower yields.
[*] Z. Liu, Prof. Dr. B. Breit
Institut fꢀr Organische Chemie
Albert-Ludwigs-Universitꢁt Freiburg
Albertstrasse 21, 79104 Freiburg im Breisgau (Germany)
E-mail: bernhard.breit@chemie.uni-freiburg.de
Supporting information and the ORCID identification number(s) for
Angew. Chem. Int. Ed. 2016, 55, 1 – 5
ꢀ 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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