γ-Hydroxynitrile alkylations: Electrophile-dependent stereoselectivity

Organic Letters

Volumn 12, Issue 13, 2010, Pages 3030-3033

  Mycka, Robert J ^a   Steward, Omar W ^a   Fleming, Fraser F ^a  

^a DUQUESNE UNIVERSITY   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

EID: 77954106102     PISSN: 15237060     EISSN: 15237052     Source Type: Journal    
DOI: 10.1021/ol101030r     Document Type: Article

References (36)

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19. The same diastereoselectivity was observed with MeMgBr indicating that there is no influence from the halide. This implies that the halide is not contained within the magnesiated nitrile nucleophile.
20. Attempts to enhance the selectivity by using t -BuMgCl (5 equiv) or combinations of t -BuMgCl and i -PrMgCl were plagued by incomplete deprotonation.
21. Intercepting the magnesiated nitrile derived from 1c with ethyl isobutyrate generates dihydroxynitrile 10c through a stereoselective reduction that similarly implies incorporation of an isopropyl group within the metalated nitrile (Scheme 3).
22. b For an excellent discussion of related alkylations with chiral organolithiums, see
23. Clayden, J. In Organolithiums: Selectivity for Synthesis; Pergamon: Amsterdam, 2002; Ch.6.
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25. The stereochemistry for each product was determined by X-ray crystallography (2h, 2i), NOESY (2g, 2j), NOE (2c), or chemical correlations (2e, 2f) as described in the Supporting Information.
26. Vu, V. A.; Marek, I.; Polborn, K.; Knochel, P. Angew. Chem., Int. Ed. 2002, 41, 351
27. Unfortunately, methods do not currently exist for generating the magnesiated nitrile from 3c for a direct comparison.
28. Presumably, the strong steric shielding in these systems overides an electrophile-dependent stereoselectivity. (6)
29. 2NLi and RMgX.
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35. 1H NMR spectrum of the crude reaction mixture.
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