Base-Dependent Regio- and Diastereoselective Alkylation of Chiral Perhydro 1,3,2-Oxazabenzophosphorinane-2-oxides Derived from (-)-8-Benzylamino Menthol

Abstract

The regioselectivity in the alkylation of chiral perhydro 1,3,2-benzoxazaphosphorinane-2-oxides is dependent on the base used for deprotonation. The ethyl oxazaphosphorinanes are ben­zylated at the nitrogen substituent after deprotonation with n-BuLi, but α to the phosphorous atom by deprotonation with LDA. On the contrary, the benzyl oxazaphosphorinane is alkylated α to the phosphorous atom after deprotonation with both, n-BuLi or LDA.

Key words

alkylation - alkyl phosphonates - asymmetric synthesis - diastereoselective reactions - 2-oxo-1,3,2-oxazaphosphorinanes

References

• For recent reviews see:
• 1a Bennani YL. Hanessian S. Chem. Soc. Rev.  1997,  97:  3161 
• 1b Kolodiazhnyi OI. Tetrahedron: Asymmetry  1998,  9:  1279 
• 1c Molt O. Schrader T. Synthesis  2002,  2633 
• 1d Ansell J. Wills M. Chem. Soc. Rev.  2002,  31:  259 
• 2a Hanessian S. Delorme D. Beaudoins S. Le Blanc Y. J. Am. Chem. Soc.  1984,  106:  5754 
• 2b Hanessian S. Andreotti D. Gomtsyan A. J. Am. Chem. Soc.  1995,  117:  10393 
• 3a Denmark SE. Marlin JE. J. Org. Chem.  1987,  52:  5742 
• 3b Denmark SE. Kim JH. Can. J. Chem.  2000,  78:  673 ; and references therein
• 4 Denmark SE. Chen C.-T. J. Am. Chem. Soc.  1995,  117:  11879 
• 5 Denmark SE. Dorow RL. J. Org. Chem.  1990,  55:  5926 
• 6 Denmark SE. Amburgey J. J. Am. Chem. Soc.  1993,  115:  10386 
• 7 Afarinkia K. Jones CL. Yu HW. Synlett  2003,  509 
• 8a Pedrosa R. Andrés C. Nieto J. Pozo S. J. Org. Chem.  2003,  68:  4923 
• 8b Pedrosa R. Andrés C. Rosón CD. Vicente M. J. Org. Chem.  2003,  1852 
• 8c Pedrosa R. Andrés C. Heras L. Nieto J. Org. Lett.  2002,  4:  2513 
• 9 Denmark SE. Kim JH. J. Org. Chem.  1995,  60:  7535 
• 10 Denmark SE. Chen C.-T. J. Org. Chem.  1994,  59:  2922 
• 11a Viljanen T. Tähtinen P. Pihlaja K. Fülöp J. J. Org. Chem.  1998,  63:  618 
• 11b Bentrude WG. Tomasz J. Synthesis  1984,  27 
• 13a Afarinkia K. Angell R. Jones CL. Lowman J. Tetrahedron Lett.  2001,  42:  743 
• 13b Bentrude WG. Setzer WN. Sopchik AE. Bajwa GS. Burright DD. Hutchinson JP. J. Am. Chem. Soc.  1986,  108:  6669 
• 15 Bennani YL. Hanessian S. Tetrahedron  1996,  52:  13837 
• 16 Afarinkia K. Jones CL. Yu H.-W. Synlett  2003,  509 
• See for instance:
• 17a Iula DM. Gawley RE. J. Org. Chem.  2000,  65:  6196 
• 17b Kopach ME. Meyers AI. J. Org. Chem.  1996,  61:  6764 
• 18 Kranz M. Denmark SE. Swiss KA. Wilson SR. J. Org. Chem.  1996,  65:  8551 

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CCDC contain supplementary crystallographic data for compounds 1 (CCDC 233645), 2 (CCDC 233647), 4 (CCDC 233644), and 8 (CCDC 233646), respectively. These data can be obtained free of charge at www.ccdc.cam.ac.uk/conts/retreiving.html or from the Cambridge Crystallographic Data Centre, 12 Union Road, Cambridge CB12 1EZ, UK; fax: (internat.) [phone]; e-mail: [e-mail].

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Typical Experimental Procedure: To a cooled (-78 °C) solution of the corresponding 1,3,2-oxazaphosphorinane (0.9 mmol) in dry THF (20 mL) under argon atmosphere was added the base (1.8 mmol), and the mixture was stirred for 30 min. Then, benzyl bromide (1.8 mmol) was added and the stirring was continued until the reaction was finished (TLC). The reaction was quenched with H₂O (9 mL) and stirred until the mixture was reached r.t. THF was removed under reduced pressure and the aqueous mixture extracted with CH₂Cl₂ (3 × 25 mL). The combined organic layers were dried (MgSO₄), filtered and concentrated. The residue was purified by flash chromatography on silica gel and hexane-EtOAc (1:2) as eluent.