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. 2016 Jul 25;55(31):9065-9.
doi: 10.1002/anie.201603465. Epub 2016 Jun 20.

Enantio- and Diastereoselective 1,2-Additions to α-Ketoesters with Diborylmethane and Substituted 1,1-Diborylalkanes

Stephanie A Murray  1 , Jacob C Green  1 , Sanita B Tailor  1 , Simon J Meek  2
Affiliations

Enantio- and Diastereoselective 1,2-Additions to α-Ketoesters with Diborylmethane and Substituted 1,1-Diborylalkanes

Stephanie A Murray et al. Angew Chem Int Ed Engl. .

Abstract

The catalytic enantioselective synthesis of boronate-substituted tertiary alcohols through additions of diborylmethane and substituted 1,1-diborylalkanes to α-ketoesters is reported. The reactions are catalyzed by readily available chiral phosphine/copper(I) complexes and produce β-hydroxyboronates containing up to two contiguous stereogenic centers in up to 99:1 e.r. and greater than 20:1 d.r. The utility of the organoboron products is demonstrated through several chemoselective functionalizations. Evidence indicates the reactions occur via an enantioenriched α-boryl-copper-alkyl intermediate.

Keywords: asymmetric catalysis; boron; copper; enantioselectivity; reaction mechanisms.

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Figures

Scheme 1
Scheme 1
Previous work: a. Catalytic enantio- and diastereoselective 1,2-addition of 1,1-diborylethane to aldehydes. This work: b. Catalytic enantio- and diastereoselective 1,2-addition of 1,1-diborylmethane and functionalized 1,1-diborylalkanes to α-ketoesters.
Scheme 2
Scheme 2
Enantio- and Diastereoselective Addition of Substituted 1,1-Diboronates to α-Ketoesters.[a] [a–c] See Table 1. [d] 1H NMR yield. L2 = (R)-(+)-5,5’,6,6’,7,7’,8,8’-octahydro-1,1’-bi-2-naphthol derived MonoPhos.
Scheme 3
Scheme 3
Representative Functionalizations of α–Boryl Tertiary Alcohols.
Scheme 4
Scheme 4
Working Catalytic Cycle for Cu-Catalyzed 1,2-Addition.
See this image and copyright information in PMC

References

    1. Quaternary Stereocenters: Challenges and Solutions for Organic Synthesis; Christophers J, Baro A, editors. Weinheim: Wiley-VCH; 2006.

    1. For recent reviews on catalytic enantioselective additions to ketones, see: Riant O, Hannedouche J. Organic & Biomolecular Chemistry. 2007;5(6):873. Shibasaki M, Kanai M. Chem. Rev. 2008;108:2853–2873.

    1. For representative examples of catalytic enantioselective additions of sp3 carbon-based nucleophiles to ketones, see: García C, LaRochelle LK, Walsh PJ. J. Am. Chem. Soc. 2002;124:10970–10971. DiMauro EF, Kozlowski MC. J. Am. Chem. Soc. 2002;124:12668–12669. Funabashi K, Jachmann M, Kanai M, Shibasaki M. Angew. Chem. Int. Ed. 2003;42:5489–5492. Angew. Chem2003, 115, 5647–5650. Betancort JM, García C, Walsh PJ. Synlett. 2004;5:749–760. Siewert J, Sandmann R, von Zezschwitz P. Angew. Chem. Int. Ed. 2007;46:7122–7124. Angew. Chem. 2007, 119, 7252–7254. Hatano M, Miyamoto T, Ishihara K. Org. Lett. 2007;9:4535–4538. Friel DK, Snapper ML, Hoveyda AH. J. Am. Chem. Soc. 2008;130:9942–9951. Madduri AVR, Harutyunyan SR, Minnaard AJ. Angew. Chem. Int. Ed. 2012;51:3164–3167. Angew. Chem. 2012, 124, 3218–3221. Rong J, Pellegrini T, Harutyunyan SR. Chem. Eur. J. 2016;22:3558–3570.

    1. Winbush SM, Roush WR. Org. Lett. 2010;12:4344–4347. Blaisdell TP, Caya TC, Zhang L, Sanz-Marco A, Morken JP. J. Am. Chem. Soc. 2014;136:9264–9267. Blaisdell TP, Morken JP. J. Am. Chem. Soc. 2015;137:8712–8715. For a recent in direct approach to 1,2-hydroxyborons, see: Chen D, Zhang X, Qi W-Y, Xu B, Xu M-H. J. Am. Chem. Soc. 2015;137:5268–5271.

    1. Joannou MV, Moyer BS, Meek SJ. J. Am. Chem. Soc. 2015;137:6176–6179. - PubMed
    2. Joannou MV, Moyer BS, Goldfogel MJ, Meek SJ. Angew. Chem. Int. Ed. 2015;54:14141–14145. Angew. Chem. 2015, 127, 14347–14351. - PubMed

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