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. 2017 May 3;139(17):6066-6069.
doi: 10.1021/jacs.7b02324. Epub 2017 Apr 20.

Synthesis of Chiral Tertiary Boronic Esters: Phosphonate-Directed Catalytic Asymmetric Hydroboration of Trisubstituted Alkenes

Suman Chakrabarty  1 , James M Takacs  1
Affiliations

Synthesis of Chiral Tertiary Boronic Esters: Phosphonate-Directed Catalytic Asymmetric Hydroboration of Trisubstituted Alkenes

Suman Chakrabarty et al. J Am Chem Soc. .

Abstract

Highly enantioselective rhodium-catalyzed hydroboration of allylic phosphonates by pinacolborane affords chiral tertiary boronic esters. The β-borylated phosphonates are readily converted to chiral β- and γ-hydroxyphosphonates and aminophosphonates and to phosphonates bearing a quaternary carbon stereocenter. The utility of the latter is illustrated by the synthesis of (S)-(+)-bakuchiol methyl ether.

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Conflict of interest statement

The authors declare no competing financial interest.

Figures

Figure 1
Figure 1
Chiral tertiary boronic esters via phosphonate-directed CAHB (nbd = norbornadiene; cod = cyclooctadiene).
Figure 2
Figure 2
Utility of phosphonate functionalized tertiary boronic esters is illustrated by selected transformations of 4a. Reagents and conditions: (a) NaBO3·4H2O; (b) (i) nBuLi, furan, −78 °C, THF; (ii) NBS; (iii) aq. Na2S2O3; (c) (i) CH2=CHMgBr, THF; (ii) I2, MeOH (iii) MeONa, MeOH; (d) (i) O3, CH2Cl2, 0 °C; (ii) Et3N, rt (e) Et3SiH, [Ru(p-cymene)Cl2]2, toluene, 50 °C; (f) (i) O3, CH2Cl2, 0 °C; (ii) Et3N; (iii) NaH2PO4, NaClO2, 2-methyl-2-butene, t-BuOH, rt; (g) (i) DPPA, toluene reflux; (ii) EtOH; (h) (i) (R)-(+)-α-methylbenzylamine, AcOH, NaCNBH3; (ii) (CF3CO)2O, Et3N, THF, rt.
Figure 3
Figure 3
Substrate scope. Note: er is determined either by chiral HPLC analysis of tertiary alcohol derivative 5 or cross-coupled derivative 7 or by NMR analysis of the amino derivative 13.
Figure 4
Figure 4
Formal total synthesis of (S)-(+)-bakuchiol. Reagents and conditions: (a) 0.25% [Rh(cod)Cl]2, 0.50% AgBF4, 0.50% (S,S)-T2, 1.1 equiv of pinBH, THF (c = 1M), rt, 12 h; (b) (i) CH2=CHMgBr, THF, −78 °C; (ii) I2, MeOH, – 78 °C; (iii) NaOMe, MeOH; (iv) Na2S2O3 (aq.); (c) TBAF, H2O; (d) DMSO, Py·SO3, Hünig’s base; (e) (CH3)2CH=PPh3; (f) Lawesson’s reagent, toluene reflux; (g) nBuLi, 4-methoxy-benzaldehyde.
Figure 5
Figure 5
Key mechanistic considerations: Graph A compares the yield of 4a over time for catalysts prepared using 1:1 (blue line) versus 2:1 (red line) T2:Rh ratios; Graph B plots percent ee of the product versus percent ee of the chiral catalyst.
See this image and copyright information in PMC

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