Communication
ChemComm
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1a-d2 (96% D) with benzyl alcohol 2a displayed the H/D-scrambled
product in 42% yield (Scheme 3b and ESI,† Scheme S5).
It is worth mentioning that all these deuterium labeling
experiments as well as the formation of H/D-scrambled products
provide evidence for the involvement of the borrowing hydrogen
strategy under manganese catalysis.12,14 Further, incorporation of
deuterium at variable amounts in the a- and b-positions in the
branched ketones also strongly supports the micro-reversible
transformation for the alkylation process. Next, we demonstrated
the rate and order of the alkylation process using kinetic studies.
The experimental outcomes displayed first order kinetics with
respect to methylene ketone 1a while considering a steady state
approximation for benzyl alcohol (ESI,† Scheme S6).
In conclusion, we have developed an inexpensive and phos-
phine free manganese-catalysed practical route for the synthesis
of branched di-substituted ketones. Utilisation of renewable
alcohols with a variety of aryl and alkyl methylene ketones yielded
the functionalised branched products in up to 84% yield. As a
highlight, we have demonstrated the sequential one-pot double
alkylation to functionalise hetero bis-alkylated ketones using
2.5 mol% Mn-catalyst. To establish the synthetic utility of the
catalytic protocol; Alzheimer’s drugs, functionalization of steroid
hormones and fatty acid derivatives has been demonstrated.
Preliminary mechanistic investigation, kinetic studies to deter-
mine the rate and order of reaction and a series of deuterium
labeling studies were performed to establish the borrowing
hydrogen approach for ketone alkylation.
7 S. Chakraborty, U. Gellrich, Y. Diskin-Posner, G. Leitus, L. Avram
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8 (a) F. Kallmeier, B. Dudziec, T. Irrgang and R. Kempe, Angew. Chem.,
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10 S. Chakraborty, U. K. Das, Y. Ben-David and D. Milstein, J. Am.
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The authors thank SERB, India (Early Career Research Award
to D. B., ECR/2015/000600), and IIT Roorkee (SMILE-32). L. M. K.
and J. D. thank IIT-R for financial support.
Conflicts of interest
There are no conflicts to declare.
11 For selected recent examples, see: (a) S. Elangovan, C. Topf, S. Fischer,
H. Jiao, A. Spannenberg, W. Baumann, R. Ludwig, K. Junge and
M. Beller, J. Am. Chem. Soc., 2016, 138, 8809; (b) V. Papa, J. R.
Cabrero-Antonino, E. Alberico, A. Spanneberg, K. Junge, H. Junge and
M. Beller, Chem. Sci., 2017, 8, 3576; (c) F. Kallmeier, T. Irrgang, T. Dietel
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Chem. Commun.
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