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. 2019 Jul 8;58(28):9434-9438.
doi: 10.1002/anie.201903308. Epub 2019 Jun 6.

Ligand-Controlled Regiodivergent Enantioselective Rhodium-Catalyzed Alkene Hydroboration

Andrew J Bochat  1 , Veronika M Shoba  1 , James M Takacs  1
Affiliations

Ligand-Controlled Regiodivergent Enantioselective Rhodium-Catalyzed Alkene Hydroboration

Andrew J Bochat et al. Angew Chem Int Ed Engl. .

Abstract

Regiocontrol in the rhodium-catalyzed boration of vinyl arenes is typically dominated by the presence of the conjugated aryl substituent. However, small differences in TADDOL-derived chiral monophosphite ligands can override this effect and direct rhodium-catalyzed hydroboration of β-aryl and β-heteroaryl methylidenes by pinacolborane to selectively produce either chiral primary or tertiary borated products. The regiodivergent behavior is coupled with enantiodivergent addition of the borane. The nature of the TADDOL backbone substituents and that of the phosphite moiety function synergistically to direct the sense and extent of regioselectivity and enantioinduction. Twenty substrates are shown to undergo each reaction mode with regioselectivity values reaching greater than 20:1 and enantiomer ratios reaching up to 98:2. A variety of subsequent transformations illustrate the potential utility of each product.

Keywords: asymmetric catalysis; homogeneous catalysis; hydroboration; regiodivergent reactions; rhodium.

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Figures

Figure 1.
Figure 1.
Regiodivergent hydroboration of alkenes.
Figure 2.
Figure 2.
Comparison of phenyl and pentafluorophenyl phosphites for a series of TADDOL backbone derivatives. Notes: the structures shown correlate to the major enantiomer from HPLC, except the product from T5b which arises from the opposite sense of π-facial selectivity.
Figure 3A-C.
Figure 3A-C.
Substrate scope: A. 4-Substituted phenyl derivatives; B. 3-Substituted phenyl and heteroaromatic derivatives; C. ortho-Substituted aryl and alkyl derivatives. Reported yields and enantiomer ratios are for the isolated alcohol after oxidation. DG = (Me2C=N-O). Notes: a used 1:1 Rh:L ratio; b yield of boronic ester before oxidation with NaBO3-H2O; c Compounds 5i, 5k, and 5l exhibited an opposite sign of optical rotation and order of elution on chiral HPLC; see SI.
Figure 4.
Figure 4.
Versatility of the primary and tertiary boronic esters 4a and 5a [DG = (Me2C=N-O)]. Reaction Conditions: (a) CsF or KF, MeCN/H2O; (b) BCl3, DCM; (c) BCl3, DCM; MIDA, DMSO; (d) LiCH2Cl, −78 °C Et2O; (e) BCl3, DCM; Raney Ni, H2, MeOH/THF; (f) NaBH3CN, MeOH/HCl; (g) LiC(OEt)=CH2, THF, −78 °C; I2; NaOMe, MeOH; (h) KF, MeCN/H2O; O2NC6H4CHO, 5 mol% [Rh(cod)Cl]2, dioxane, 80 °C; DMP, DCM; (i) 12 or 13, HCl/H2O/MeOH, 40 °C; (j) thiophene, nBuLi, THF, −78 °C; NBS; (k) PhBr, 15 mol% Pd(OAc)2, 15 mol% BINAP, KOH, THF/H2O, 100 °C; (l) TBAF, toluene; (m) MeON(H)Li, THF, 60 °C; Boc2O; (n) H2O2, NaOH, MeOH/H2O; Raney Ni, H2
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