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. 2017 Jul 1;8(7):4840-4847.
doi: 10.1039/c7sc01218g. Epub 2017 May 4.

Single operation palladium catalysed C(sp3)-H functionalisation of tertiary aldehydes: investigations into transient imine directing groups

S St John-Campbell  1 , A J P White  1 , J A Bull  1
Affiliations

Single operation palladium catalysed C(sp3)-H functionalisation of tertiary aldehydes: investigations into transient imine directing groups

S St John-Campbell et al. Chem Sci. .

Abstract

Simple amine and diamine derivatives can promote the palladium catalysed direct β-C-H arylation of aliphatic aldehydes via transient imine formation. Trifluoroacetate was shown to be crucial in promoting the reaction. Sub-stoichiometric quantities of simple N-tosylethylenediamine was shown to form a bidentate directing group with an imine linkage. Isolation of an unsymmetrical palladacycle has shown different potential binding modes of the secondary NTs coordinating group by single crystal X-ray diffraction analysis, suggestive of a hemilabile ligand.

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Figures

Scheme 1
Scheme 1. Transient directing groups for C–H arylation of aldehydes.
Fig. 1
Fig. 1. Proposed directing group structure.
Scheme 2
Scheme 2. Screen of bidentate and monodentate directing groups for the arylation of pivaldehyde derived imines. aYields quoted as combined yield for 3a–c, with separate mono-, di- and triarylated yields quoted below. Yields determined by 1H NMR using 1,3,5-trimethoxybenzene as an internal standard.
Scheme 3
Scheme 3. Screen of bidentate and monodentate directing groups for the direct arylation of pivaldehyde. Reaction conditions: pivaldehyde (0.2 mmol), 4-iodoanisole (2.6 equiv.), HFIP : AcOH (1 : 1, 0.5 M). aYields quoted as combined yield for 3a–c, with separate mono-, di- and triarylated yields quoted below. Yields determined by 1H NMR using 1,3,5-trimethoxybenzene as an internal standard.
Scheme 4
Scheme 4. Scope of aryl iodides to form aldehydes 3–12. Reaction conditions: pivaldehyde (0.4 mmol), 1a (0.5 equiv.), Ar-I (2.6 equiv.), HFIP : AcOH (1 : 1, 0.5 M). Yields correspond to sum of yields of isolated products, with individual yields a–c given below. aReaction time of 24 h. bIsolated as a mixture of di- and tri-arylated products. cUsing 1x in place of 1a. dReaction time of 6 h.
Scheme 5
Scheme 5. Reaction scope varying the aldehyde. Ar = C6H4OMe. Reaction conditions: aldehyde (0.4 mmol), 1a (0.5 equiv.), 4-iodoanisole (2.6 equiv.), HFIP : AcOH (1 : 1, 0.5 M). Yields correspond to sum of yields of isolated products, with individual yields a and b given below. aUsing 1x in place of 1a.
Scheme 6
Scheme 6. Arylation of 3a and 3b. Conditions: 3a (0.099 mmol) or 3b (0.064 mmol), 1a (0.5 equiv.), 4-iodoanisole (2.6 equiv.), Pd(OPiv)2 (5 mol%), AgTFA (2 equiv.), DMSO (1 equiv.), HFIP : AcOH (1 : 1, 0.5 M), 130 °C, 3 h. Yields determined by 1H NMR using 1,3,5-trimethoxybenzene as an internal standard.
Scheme 7
Scheme 7. Formation and reactions of 2a-Pd-dimer. aConditions: 2a-Pd-dimer (0.04 mmol), 4-iodoanisole (6.0 equiv.), AgOAc (4.0 equiv.), AcOH (0.3 M), 120 °C, 24 h. bConditions: pivaldehyde (0.2 mmol), 1a (0.5 equiv.), 4-iodoanisole (2.6 equiv.), 2a-Pd-dimer (2.5 mol%), AgTFA (2.0 equiv.), HFIP : AcOH (1 : 1, 0.5 M), 130 °C, 3 h. cYields determined by 1H NMR using 1,3,5-trimethoxybenzene as an internal standard.
Fig. 2
Fig. 2. Crystal structure of 2a-Pd-dimer. Selected bond lengths (Å), Pd1–C1 2.009(3), Pd1–N4 1.952(3), Pd1–N7 2.253(3), Pd1–O41 2.046(2), Pd2–N7 2.085(3), Pd2–C21 2.003(3), Pd2–N24 2.018(3), Pd2–O43 2.244(2). The Pd1···Pd2 separation is 3.1098(3) Å.
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