Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2020 Feb 10;59(7):2875-2880.
doi: 10.1002/anie.201913563. Epub 2019 Dec 30.

Peptide-Catalyzed Fragment Couplings that Form Axially Chiral Non-C2 -Symmetric Biaryls

Gavin Coombs  1 , Marcus H Sak  1 , Scott J Miller  1
Affiliations

Peptide-Catalyzed Fragment Couplings that Form Axially Chiral Non-C2 -Symmetric Biaryls

Gavin Coombs et al. Angew Chem Int Ed Engl. .

Abstract

We have demonstrated that small, modular, tetrameric peptides featuring the Lewis-basic residue β-dimethylaminoalanine (Dmaa) are capable of atroposelectively coupling naphthols and ester-bearing quinones to yield non-C2 -symmetric BINOL-type scaffolds with good yields and enantioselectivity. The study culminates in the asymmetric synthesis of backbone-substituted scaffolds similar to 3,3'-disubstituted BINOLs, such as (R)-TRIP, with good (94:6 e.r.) to excellent (>99.9:0.1 e.r.) enantioselectivity after recrystallization, and a diastereoselective net arylation of the minimally modified nonsteroidal anti-inflammatory drug (NSAID) naproxen.

Keywords: atropisomerism; biaryl compounds; organocatalysis; peptides; quinones.

PubMed Disclaimer

Figures

Scheme 1.
Scheme 1.
Approaches toward construction of enantioenriched atropisomers via naphthol-quinone coupling.
Scheme 2.
Scheme 2.
Showcase examples of BINOL-type brominated biaryls synthesized via peptide-catalyzed quinone arylation.
Scheme 3.
Scheme 3.
Substrate Scope.[a] [a] Isolated yield; e.r. determined by CSP-HPLC (254 nm, uncorrected). Average of two trials. Absolute configuration shown as (S) and assigned in analogy to the data reported by Tan and co-workers[9] (see Section 6.5 in Supporting Information for details). A. Variations in quinone coupling partner. B. Variations in naphthol coupling partner. Numbering is shown on the naphthol partner for convenience. C. Variations in both coupling partners. Additional coupling partners are boxed. PMB = p-methoxybenzyl.
Scheme 4.
Scheme 4.
Applications of this method. [a] 1 equiv of quinone and 1 equiv of naphthol were used in the reaction. Reported e.r. and yields are from one trial). [b] X-ray crystal structures verifying the connectivity of products 3s and 3t (crystallographic data gathered on racemic crystals). [c] Average of two trials; d.r. determined by 1H NMR integrations (see Section 7.6 of the Supporting Information).
See this image and copyright information in PMC

References

    1. Bringmann G, Price Mortimer AJ, Keller PA, Gresser MJ, Garner J, Breuning M, Angew. Chem. Int. Ed 2005, 44, 5384–5427; - PubMed
    2. Wang Y-B, Tan B, Acc. Chem. Res 2018, 51, 534–547. - PubMed
    1. Brussee J, Jansen ACA, Tetrahedron Lett. 1983, 24, 3261–3262;
    2. Lloyd-Williams P, Giralt E, Chem. Soc. Rev 2001, 30, 145–157;
    3. Hassan J, Sévignon M, Gozzi C, Schulz E, Lemaire M, Chem. Rev 2002, 102, 1359–1470; - PubMed
    4. Nelson TD, Crouch RD, Organic Reactions 2004, 63, 265–555;
    5. Wencel-Delord J, Panossian A, Leroux FR, Colobert F, Chem. Soc. Rev 2015, 44, 3418–3430; - PubMed
    6. Liao G, Zhou T, Yao Q-J, Shi B-F, Chem. Commun 2019, 55, 8514–8523. - PubMed
    1. Bringmann G, Breuning M, Tasler S, Synthesis 1999, 1999, 525–558;
    2. Bringmann G, Menche D, Acc. Chem. Res 2001, 34, 615–624; - PubMed
    3. Bringmann G, Breuning M, Pfeifer R-M, Schenk WA, Kamikawa K, Uemura M, J. Organomet. Chem 2002, 661, 31–47;
    4. Bringmann G, Tasler S, Pfeifer R-M, Breuning M, J. Organomet. Chem 2002, 661, 49–65;
    5. Bringmann G, Scharl H, Maksimenka K, Radacki K, Braunschweig H, Wich P, Schmuck C, Eur. J. Org. Chem 2006, 2006, 4349–4361.
    1. Kakiuchi F, Le Gendre P, Yamada A, Ohtaki H, Murai S, Tetrahedron: Asymmetry 2000, 11, 2647–2651;
    2. Miyaji R, Asano K, Matsubara S, J. Am. Chem. Soc 2015, 137, 6766–6769; - PubMed
    3. Yu C, Huang H, Li X, Zhang Y, Wang W, J. Am. Chem. Soc 2016, 138, 6956–6959. - PubMed
    1. Gustafson JL, Lim D, Miller SJ, Science 2010, 328, 1251–1255; - PMC - PubMed
    2. Barrett KT, Miller SJ, J. Am. Chem. Soc 2013, 135, 2963–2966; - PMC - PubMed
    3. Diener ME, Metrano AJ, Kusano S, Miller SJ, J. Am. Chem. Soc 2015, 137, 12369–12377; - PMC - PubMed
    4. Metrano AJ, Abascal NC, Mercado BQ, Paulson EK, Miller SJ, Chem. Commun 2016, 52, 4816–4819. - PMC - PubMed

Publication types

LinkOut - more resources