Vladimir Birman

Vladimir Birman

​Associate Professor of Chemistry
Postdoctoral Fellow, Columbia
PhD, University of Chicago
BS, University of North Carolina at Charlotte
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    • Washington University
    • CB 1134
    • One Brookings Dr.
    • St. Louis, MO 63130-4899
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    Our group’s research efforts range from total synthesis of bioactive natural products to asymmetric catalysis.  In summary, we are interested both in devising concise and efficient strategies for synthesizing complex molecules and in designing simple molecules that enable new and useful transformations.

    In 2004, we completed total syntheses of the unusual marine alkaloid sceptrin.[1]  In 2007, we disclosed a regioselective synthesis of the antibiotic prekinamycin,[2] utilizing a novel annulation reaction and an enantioselective synthesis of the alkaloid lobeline[3] via the desymmetrization of a meso-diol precursor using one of our catalysts, BTM (see below). In 2016, we achieved a concise enantioselective synthesis of the meroterpenoid lingzhiol[4] featuring a biogenetically-inspired semipinacol rearrangement.

    Figure 1. Completed synthetic targets

     

    Our efforts in the area of asymmetric catalysis concentrate on enantioselective acyl transfer.  Our group has developed a new class of enantioselective acyl transfer catalysts (ABCs, for Amidine-Based Catalysts, Figure 2).[5]  These compounds, easily obtained from commercially available starting materials, are highly effective in the kinetic resolution (KR) of several classes of chiral secondary alcohols (Figure 3).[6]  In addition, we have demonstrated for the first time the KR of chiral lactams and thiolactams via catalytic, enantioselective N-acylation.[7] The enantioselectivities observed in all these cases are consistent with a transition state model based on cation-p interactions between the acylated intermediate and the substrate. Our computational studies in collaboration with the Houk group (UCLA) support this hypothesis.[8] ABCs have also proved effective in promoting enantioselective alcoholysis of several classes of racemic acyl donors (Figure 4).[9] Some of these reactions proceed in the dynamic kinetic resolution (DKR) mode converting both enantiomers of the starting material into a single enantiomer of the product.

    Figure 2. Evolution of amidine-based catalysts (ABCs)

     

    Figure 3. Enantioselective catalytic acylation promoted by ABCs

     

    Figure 4. Enantioselective catalytic alcoholysis promoted by ABCs

     

    Recently, we began exploring a different type of applications of ABCs: cascade reactions accompanied by generation of new stereocenters. We have disclosed a highly enantioselective transformation of thioesters into chiral thiochromenes requiring no additional reagents and giving off carbon dioxide as the only byproduct (Figure 5a).[10a] Interestingly, a closely related rearrangement of thioesters into tricyclic thiochromanes (Figure 5b) proceeded very slowly with HBTM-2. By contrast, the electron-rich catalyst H-PIP (shown) displayed excellent rates and enantioselectivities in this reaction.[10b]

    Figure 5. Enantioselective rearrangement of thioesters promoted by ABCs

     

    Another useful application of ABCs that we have developed recently is the enantio- and diastereo-selective synthesis of α-fluoro-β-amino acid derivatives by way of fluorinated β-lactams (Figure 6)[11].

     

    Figure 6. Synthesis of alpha-fluoro-beta-amino acid esters

     

    Besides chiral nucleophilic catalysts (i.e., Lewis bases), enantioselective acylation reactions have often been catalyzed by chiral Lewis acids. Application of chiral Brønsted acids to these processes has remained unknown until recently, when we demonstrated that a BINOL phosphoric acid provides excellent ees in the DKR of azlactones (Figure 7).[12]

     

    Figure 7. Chiral Bronsted acid-catalyzed dynamic kinetic resolution of azlactones

     

    Apart from our studies in asymmetric catalysis, we have developed a new class of stoichiometric chiral hypervalent iodine reagents oxidizing o-alkylphenols with significant levels of asymmetric induction (Figure 8).[13]  The intermediate o-quinols thus generated undergo spontaneous Diels-Alder dimerization with complete regio- and diastereoselectivity producing tricyclic final products adorned with 6 stereocenters.  Compounds of this type have been found in Nature. 

    Figure 8. Enantioselective oxidation of o-alkylphenols with chiral o-iodoxyphenyl-oxazolines

     

    For more details and other projects pursued in our group, please see additional references provided in the CV.

    REFERENCES

     

      [1] Birman, V. B.; Jiang, X.-T. Org. Lett. 2004, 6, 2369. DOI: 10.1021/ol049283g
      [2] Birman, V. B.; Zhao, Z.; Guo, L. Org. Lett. 2007, 9, 1223. DOI: 10.1021/ol0629768
      [3]  Birman, V. B.; Jiang, H.; Li, X. Org. Lett. 2007, 9, 3237. DOI: 10.1021/ol071064i
      [4] Sharmah Gautam, K.; Birman, V. B. Org. Lett. 2016, 18, 1499. DOI: 10.1021/acs.orglett.5b03212
      [5] For a review, see: Birman, V. B. Aldrichimica Acta 2016, 49, 23.
      [6] Li, X.; Jiang, H.; Uffman, E. W. Guo, L.; Zhang, Y.; Yang, X.; Birman, V. B. J. Org. Chem. 2012, 77, 1722. DOI: 10.1021/jo202220x and references cited therein.
      [7] Yang, X.; Bumbu, V. D.; Liu, P.; Li, X.; Jiang, H.; Uffman, E. W. Guo, L.; Zhang, W.; Jiang, X.; Houk, K. N.; Birman, V. B. J. Am. Chem. Soc., 2012, 134, 17605. DOI: 10.1021/ja306766n and references cited therein.
      [8] Li, X.; Liu, P.; Houk, K. N.; Birman, V. B. J. Am. Chem. Soc. 2008, 130, 13836. DOI: 10.1021/ja805275s
      [9] (a) Yang, X.; Birman, V. B. Chem. Eur. J. 2011, 17, 11296. DOI: 10.1002/chem.201101028 and references cited therein. (b) Yang, X.; Lu, G.; Birman, V. B. Org. Lett. 2010, 12, 892. DOI: 10.1021/ol902969j (c) Bumbu, V. D.; Birman, V. B. J. Am. Chem. Soc. 2011, 133, 

    13902. DOI: 10.1021/ja2058633 (d) Bumbu, V. D.; Yang, X.; Birman, V. B. Org. Lett. 2013, 15, 2790. DOI: 10.1021/ol401122g
      [10] (a) Ahlemeyer, N. A.; Birman, V. B. Org. Lett. 2016, 18, 3454 DOI: 10.1021/acs.orglett.6b01639 (b) Ahlemeyer, N. A.; Streff, E. V.; Muthupandi, P.; Birman, V. B. Org. Lett. 2017, 19, 6486. DOI:10.1021/acs.orglett.7b03044
      [11] Straub, M. R.; Birman, V. B. Org. Lett. 2018, 20, 7550. DOI: 10.1021/acs.orglett.8b03297
      [12] Lu, G.; Birman, V. B. Org. Lett. 2011, 13, 356. DOI: 10.1021/ol102736t 
      [13] Boppisetti, J. K.; Birman, V. B. Org. Lett. 2009, 11, 1221. DOI: 10.1021/ol8029092