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. 2012 Oct 10;134(40):16856-68.
doi: 10.1021/ja307861n. Epub 2012 Oct 1.

Stereospecific cross-coupling of secondary organotrifluoroborates: potassium 1-(benzyloxy)alkyltrifluoroborates

Gary A Molander  1 , Steven R Wisniewski
Affiliations

Stereospecific cross-coupling of secondary organotrifluoroborates: potassium 1-(benzyloxy)alkyltrifluoroborates

Gary A Molander et al. J Am Chem Soc. .

Abstract

Potassium 1-(alkoxy/acyloxy)alkyltrifluoroborates have been synthesized through a copper-catalyzed diboration of aldehydes and subsequent conversion of the resulting potassium 1-(hydroxy)alkyltrifluoroborates. The palladium-catalyzed Suzuki-Miyaura reaction employing the potassium 1-(benzyloxy)alkyltrifluoroborates with aryl and heteroaryl chlorides provides access to protected secondary alcohols in high yields. The β-hydride elimination pathway is avoided through use of the benzyl protecting group, which is proposed to stabilize the diorganopalladium intermediate by coordination of the arene to the metal center. This cross-coupling is stereospecific with complete retention of stereochemistry.

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Conflict of interest statement

Notes

The authors declare no competing financial interest.

Figures

Figure 1
Figure 1
Proposed coordination from benzyl stabilizing group.
Figure 2
Figure 2
Graphical summary of Screen #1. Reaction conditions: 1.0 equiv of 7a, 1.0 equiv of 4-chloroanisole, 0.1 equiv of palladium, 110 °C, 3.0 equiv of Cs2CO3, 24 h. (Pd-L = L-Pd-G2, Cat A = cataCXium A, tamylOH = tert-amyl alcohol)
Figure 3
Figure 3
Graphical summary of Screen #2. Reaction conditions: 1.0 equiv of 7a, 1.0 equiv of 4-chloroanisole, 0.1 equiv of palladium, 0.2 equiv of cataCXium A, 3.0 equiv of Cs2CO3, 110 °C, 24 h.
Figure 4
Figure 4
Graphical summary of Screen #3. Only the top ten ligands are shown. Reaction conditions: 1.0 equiv of 7a, 1.0 equiv of 4-chloroanisole, 0.1 equiv of palladium, 0.2 equiv of L, 3.0 equiv of Cs2CO3, 110 °C, 24 h. (Pd-L = L-Pd-G2)
Figure 5
Figure 5
Graphical summary of Screen #4. Reaction conditions: 1.0 equiv of 7a, 1.0 equiv of 4-chloroanisole, 0.075 equiv of palladium, 105 °C, 24 h. (A = [Pd(allyl)Cl]2 with cataCXium A, B = cataCXium A-Pd-G2, 1:0/1:1/1:2 = palla-dium:ligand ratio)
Scheme 1
Scheme 1
Disconnections to Access Secondary Alcohols.
Scheme 2
Scheme 2
Proposed Catalytic Cycle for Diboration of Aldehydes with Methanol
Scheme 3
Scheme 3
Possible pathways after transmetalation of the organoboron
Scheme 4
Scheme 4
Proposed Mechanism for the Coupling of Alkyl β-Trifluoroboratoamides
Scheme 5
Scheme 5
Synthesis of Enantioenriched Potassium (S)-1-(Benzyloxy)-3-phenylpropyltrifluoroborate
Scheme 6
Scheme 6
Stereospecificity of Various Suzuki-Miyaura Cross-Coupling Reactions
See this image and copyright information in PMC

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