Expeditious synthesis of 1-aminoindane derivatives achieved by [1,4]-hydride shift mediated C(sp3)-H bond functionalization

Article abstract of DOI:10.1039/c4cc00894d

Described herein is a [1,4]-hydride shift mediated expeditious synthesis of 1-aminoindane derivatives. A wide variety of substrates could be employed in this reaction to afford various indane derivatives in good to excellent chemical yields. Examination of the amine moiety revealed that the sterically hindered amine is the key to achieving both low catalyst loading and excellent chemical yields. This journal is the Partner Organisations 2014.

Full text of DOI:10.1039/c4cc00894d

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Expeditious synthesis of 1-aminoindane
derivatives achieved by [1,4]-hydride shift
Cite this: Chem. Commun., 2014,
50, 3729
mediated C(sp3)–H bond functionalization†
Received 3rd February 2014,
Accepted 13th February 2014
Keiji Mori, Kazuki Kurihara and Takahiko Akiyama*
DOI: 10.1039/c4cc00894d
www.rsc.org/chemcomm
Described herein is a [1,4]-hydride shift mediated expeditious
synthesis of 1-aminoindane derivatives. A wide variety of substrates
could be employed in this reaction to afford various indane derivatives
in good to excellent chemical yields. Examination of the amine moiety
revealed that the sterically hindered amine is the key to achieving both
low catalyst loading and excellent chemical yields.
Scheme 1 C(sp3)–H bond functionalization via an internal redox process.
The development of a method for the direct functionalization
of relatively unreactive C–H bonds has become a major target of
research.1 Recently, the C(sp3)–H bond functionalization by the
hydride shift/cyclization process, namely, the ‘‘internal redox
process,’’ has attracted much attention due to its unique features
(Scheme 1).2 The key feature of this transformation is the [1,5]-hydride
shift of the C(sp3)–H bond a to the heteroatom. Subsequent 6-endo
cyclization to the cation species affords heterocycle 2.3 Although C–H
bond functionalization is promoted by a transition metal catalyst in
most cases, this type of C–H bond functionalization typically proceeds
under thermal conditions or Brønsted or Lewis acid catalysis.
In this process, the low catalyst loading of Yb(OTf)3 (5 mol%) sufficed
to promote the desired transformation to afford 1-aminoindane
derivatives in good to excellent chemical yields.
(1)
The desired [1,4]-hydride shift process was realized when
benzylidene malonate 3 was employed as the substrate. Upon
Recent advances in the internal redox process have enabled the treatment of 3a with 5 mol% Yb(OTf)3 in refluxing ClCH2CH2Cl, the
construction of an array of useful skeletons.4–7 An enantioselective desired reaction proceeded smoothly to afford indane derivative 4a in
variant of the reaction was also realized by using both a chiral metal a quantitative yield with a short reaction time (0.5 h).10 The substrate
catalyst and an organocatalyst, affording synthetically useful chiral scope of this reaction is summarized in Fig. 1. Investigation of the
tetrahydroquinoline derivatives with excellent enantioselectivities.8 amine moiety revealed that the bulkiness of the substituent on the
Contrary to the dramatic advances offered by the [1,5]-hydride shift nitrogen atom played a critical role in the reactivity; whereas 30 mol%
process, the corresponding [1,4]-hydride shift process, which also Yb(OTf)3 was required to afford N,N-diethylamine derivative 4b and
generates synthetically useful skeletons, has not been well investi- 5 mol% of the same catalyst sufficed for N,N-diisopropylamine
gated. To the best of our knowledge, there are only two precedents in derivative 3a. Relatively bulky amines, such as N,N-dibenzyl, diphenyl,
which two equivalents of a transition metal additive (CuBr)9a or and diallyl amines 3c–e, underwent the reaction to give indanes 4c–e
strong electronic assistance from two heteroatoms9b was required.
in good to excellent chemical yields with a low catalyst loading
We wish to report herein a [1,4]-hydride shift triggered C(sp3)–H (5 mol%).11 This reactivity control by the steric effect was much more
bond functionalization from simple benzylamine derivatives. prominent in cyclic amine derivatives. Although almost no appreci-
able product was generated using piperidine substrate 3f (30 mol%
Department of Chemistry, Faculty of Science, Gakushuin University, 1-5-1 Mejiro,
Toshima-ku, Tokyo 171-8588, Japan. E-mail: takahiko.akiyama@gakushuin.ac.jp;
Fax: (+81) 3-5992-1029; Tel: (+81) 3-5992-1029
Yb(OTf)3, 24 h), 3g with 2,2,6,6-tetramethylpiperidine (an extremely
bulky amine) enabled the smooth formation of desired adduct 4g
using a 5 mol% catalyst (ring-opened product 4h was also obtained
and the combined yield is shown in Fig. 1, 4g :4h = 2.3:1). Isoquino-
line derivative 4i was obtained in moderate yield with a low catalyst
loading (61%, 5 mol%).
† Electronic supplementary information (ESI) available: Experimental procedures
and characterization data for all new compounds. CCDC 980641–980643. For ESI
and crystallographic data in CIF or other electronic format see DOI: 10.1039/
c4cc00894d
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Fig. 2 Rationalization for enhancement of reactivity by the bulky amine
moiety.
Furthermore, the bulky amine moiety would prevent the nucleo-
philic attack of nitrogen. As a result of these two factors, the
reactivity of bulky amines was improved dramatically.12
Because benzylamine derivative 3 has some hydrogens adjacent
to the nitrogen atom (Ha and Hb in Scheme 3), two reaction
pathways could be assumed for the formation of key iminium
cation intermediate E (Scheme 3): (1) the [1,4]-hydride shift path-
way (path A) and (2) the pathway involving the [1,6]-hydride shift
([1,6]-H shift followed by isomerization, path B).
To clarify the detailed reaction course, a D-labeling experi-
ment was conducted. The fact that deuterium incorporation
was observed only at the benzylic position (498% D) led us to
unambiguously rule out the latter pathway.
Fig. 1 Substrate scope of the [1,4]-H shift/cyclization sequence.
Most of the internal redox reactions are considered to proceed
via the intramolecular hydride shift process, although the inter-
molecular hydride shift mechanism is proposed in some cases.6e,f
In order to ensure the intramolecular nature of the hydride shift
process, we conducted a crossover experiment between d-3a and
3o (Scheme 4). The deuterium incorporation was observed in only
d-4a, which revealed that this hydride shift proceeded intramole-
cularly. Furthermore, the observation of the primary kinetic
isotope effect (kH/D = 3.2) suggested that the hydride shift process
was the rate-determining step in the reaction.
The substituent on the aromatic ring did not have an impact on
the reaction, and the corresponding adducts (4j–n) were obtained
in good to excellent chemical yields with the 5 mol% catalyst (the
amine moiety was fixed to N,N-dibenzylamine).
Next, we attempted to decrease the catalyst loading of less reactive
substrates (such as 3b with an N,N-diethylamine moiety) by employing
more reactive benzylidene barbiturate 6. When aldehyde 5 was mixed
with 1,3-dimethylbarbituric acid in EtOH at room temperature, 5 was
almost completely consumed in 1 h. The resulting product, however,
was not desired benzylidene barbiturate 6 but zwitterionic compound
7 (intramolecular cyclization adduct).11 This result indicates that the
nitrogen in 6 has the propensity to attack the activated electrophilic
carbon of the hydride acceptor (Scheme 2).
In summary, we have developed an expeditious synthesis of
1-aminoindane derivatives by [1,4]-hydride shift mediated
Based on this result, the high reactivity of bulky amine deriva-
tives could be rationalized by taking two factors into consideration:
(1) control of the conformational behavior of the benzylamine
moiety and (2) suppression of the intramolecular nucleophilic
attack (Fig. 2). The desired [1,4]-hydride shift would be promoted
via conformer B, wherein benzylic hydrogens would be located in
the vicinity of the electrophilic a carbon of benzylidene malonate.
In the case of 3a, the conformational equilibrium would be shifted
markedly to desired conformer B because of the steric repulsion
between the bulky diisopropylamine moiety and the malonate group.
Scheme 3 Clarification of the reaction mechanism of the [1,4]-hydride
Scheme 2 Formation of a zwitterionic species.
3730 | Chem. Commun., 2014, 50, 3729--3731
shift/cyclization sequence.
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C(sp3)–H bond functionalization. A wide variety of substrates were
applicable to this reaction and various 1-aminoindane derivatives
were obtained in good to excellent chemical yields. The salient
feature of this reaction is that the bulky amine significantly
enhanced the reactivity, which could be rationalized by two
factors: (1) control of the conformational behavior of the benzyl-
amine moiety and (2) suppression of the intramolecular nucleo-
philic attack. Detailed investigation of the reaction mechanism
suggested that the [1,4]-hydride shift was the rate-determining
step and occurred intramolecularly. Further investigation toward
the development of new reactions by exploiting the [1,4]-hydride
shift/cyclization sequence is underway in our laboratory.
This work was partially supported by a Grant-in-Aid for
Scientific Research on Innovative Areas ‘‘Advanced Transforma-
tion Organocatalysis’’ from MEXT, Japan.
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dibenzylamine to the optimum conditions (10 mol% Yb(OTf)3,
ClCH2CH2Cl, reflux) resulted in a moderate chemical yield (55%)
of the indane derivative. This clearly indicates the reversibility from
zwitterionic compound to benzylidene barbiturate.
This journal is ©The Royal Society of Chemistry 2014
Chem. Commun., 2014, 50, 3729--3731 | 3731