Crystal engineering rescues a solution organic synthesis in a cocrystallization that confirms the configuration of a molecular ladder

Manza B J Atkinson; S V Santhana Mariappan; Dejan-Krešimir Bučar; Jonas Baltrusaitis; Tomislav Friščić; Naif G Sinada; Leonard R MacGillivray

doi:10.1073/pnas.1104352108

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Crystal engineering rescues a solution organic synthesis in a cocrystallization that confirms the configuration of a molecular ladder

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Crystal engineering rescues a solution organic synthesis in a cocrystallization that confirms the configuration of a molecular ladder

Manza B J Atkinson, S V Santhana Mariappan, Dejan-Krešimir Bučar, Jonas Baltrusaitis, Tomislav Friščić, Naif G Sinada and Leonard R MacGillivray

Proceedings of the National Academy of Sciences - PNAS, Vol.108(27), pp.10974-10979

07/05/2011

DOI: 10.1073/pnas.1104352108

PMCID: PMC3131360

PMID: 21690362

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Abstract

Treatment of an achiral molecular ladder of C(2h) symmetry composed of five edge-sharing cyclobutane rings, or a [5]-ladderane, with acid results in cis- to trans-isomerization of end pyridyl groups. Solution NMR spectroscopy and quantum chemical calculations support the isomerization to generate two diastereomers. The NMR data, however, could not lead to unambiguous configurational assignments of the two isomers. Single-crystal X-ray diffraction was employed to determine each configuration. One isomer readily crystallized as a pure form and X-ray diffraction revealed the molecule as being achiral based on C(i) symmetry. The second isomer resisted crystallization under a variety of conditions. Consequently, a strategy based on a cocrystallization was developed to generate single crystals of the second isomer. Cocrystallization of the isomer with a carboxylic acid readily afforded single crystals that confirmed a chiral ladderane based on C(2) symmetry. The chiral ladderane and acid self-assembled to generate a five-component hydrogen-bonded complex that packs to form large solvent-filled homochiral channels of nanometer-scale dimensions. Whereas cocrystallizations are frequently applied to structure determinations of proteins, our study represents the first application of a cocrystallization to confirm the relative configuration of a small-molecule diastereomer generated in a solution-phase organic synthesis.

Details

Title: Subtitle: Crystal engineering rescues a solution organic synthesis in a cocrystallization that confirms the configuration of a molecular ladder
Creators: Manza B J Atkinson - Department of Chemistry, University of Iowa, Iowa City, IA 52242-1294, USA
S V Santhana Mariappan
Dejan-Krešimir Bučar
Jonas Baltrusaitis
Tomislav Friščić
Naif G Sinada
Leonard R MacGillivray
Resource Type: Journal article
Publication Details: Proceedings of the National Academy of Sciences - PNAS, Vol.108(27), pp.10974-10979
DOI: 10.1073/pnas.1104352108
PMID: 21690362
PMCID: PMC3131360
NLM abbreviation: Proc Natl Acad Sci U S A
ISSN: 0027-8424
eISSN: 1091-6490
Publisher: National Academy of Sciences
Language: English
Date published: 07/05/2011
Academic Unit: Pharmaceutical Sciences and Experimental Therapeutics; Chemistry
Record Identifier: 9984217459002771

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