Asymmetric Synthesis of (S,S)- and (R,R)-2-Methylthreitol

Abstract

The asymmetric synthesis of (S,S)- and (R,R)-2-methylthreitol was carried out, starting from the SAMP or RAMP hydrazone of 2,2-dimethyl-1,3-dioxan-5-one. The protocol involves an enantioselective α-alkylation as a key step. The second stereogenic center was installed by either nucleophilic 1,2-addition or diastereo­selective epoxidation with bis(acetylacetonato)oxovanadium(IV) [VO(acac)₂] as catalyst. The title compounds were obtained in excellent diastereo- and enantiomeric excesses (≥98% de, 98% ee) and in good overall yields (40-61%).

asymmetric synthesis - epoxidation - tetrols - α-alkylation - SAMP/RAMP hydrazones - 1,2-addition

References

<A NAME="RZ02307SS-1A">1a</A> Testa CA. Cornish RM. Poulter CD. J. Bacteriol.  2004,  186:  473 

<A NAME="RZ02307SS-1B">1b</A> Seemann M. Tse Sum Bui B. Wolff M. Tritsch D. Campos N. Boranat A. Marquet A. Rohner M. Angew. Chem. Int. Ed.  2002,  41:  4337 ; Angew. Chem. 2002, 114, 4513

<A NAME="RZ02307SS-1C">1c</A> Urbansky M. Davis CE. Surjan JD. Coates RM. Org. Lett.  2004,  6:  135 

<A NAME="RZ02307SS-1D">1d</A> Koppisch AT. Blagg BSJ. Poulter CD. Org. Lett.  2000,  2:  215 

<A NAME="RZ02307SS-1E">1e</A> Rodriguez-Conceptión M. Forés O. Martinez-Garcia JF. González V. Philipps MA. Ferrer A. Boronat A. Plant Cell  2004,  16:  144 

<A NAME="RZ02307SS-1F">1f</A> Hoeffler J.-F. Pale-Grosdemange C. Rohmer M. Tetrahedron Lett.  2000,  56:  1485 

<A NAME="RZ02307SS-2">2</A> Kis K. Wungsintaweekul J. Eisenreich W. Zenk MH. Bacher A. J. Org. Chem.  2000,  65:  587 

<A NAME="RZ02307SS-3">3</A> Fontana A. Messina R. Spinella A. Cimino G. Tetrahedron Lett.  2000,  41:  7559 

<A NAME="RZ02307SS-4A">4a</A> Andrae MO. Crutzen PJ. Science  1997,  276:  1052 

<A NAME="RZ02307SS-4B">4b</A> Claeys M. Graham B. Vas G. Wang W. Vermeylen R. Pashynska V. Cafmeyer J. Guyon P. Andrae MO. Artaxo P. Maenhaut W. Science  2004,  303:  1173 

<A NAME="RZ02307SS-5">5</A> Giner J.-L. Ferris WV. Mullins JJ. J. Org. Chem.  2002,  67:  4856 

<A NAME="RZ02307SS-6">6</A>

Moen, A. R.; Ruud, K.; Anthonsen, T. Eur. J. Org. Chem., 2007, 1262.

For a review, see:

<A NAME="RZ02307SS-7A">7a</A> Enders D. Voith M. Lenzen A. Angew. Chem. Int. Ed.  2005,  44:  1304 ; Angew. Chem. 2005, 117, 1330

<A NAME="RZ02307SS-7B">7b</A> Enders D. Voith M. Ince S. Synthesis  2002,  1775 

For organocatalytic applications of dioxanone, see:

<A NAME="RZ02307SS-8A">8a</A> Enders D. Grondal C. Angew. Chem. Int. Ed.  2005,  44:  1210 ; Angew. Chem. 2005, 117, 1235

<A NAME="RZ02307SS-8B">8b</A> Enders D. Grondal C. Vrettou M. Raabe G. Angew. Chem. Int. Ed.  2005,  44:  4079 ; Angew. Chem. 2005, 117, 4147

<A NAME="RZ02307SS-8C">8c</A> Enders D. Grondal C. Tetrahedron  2006,  62:  329 

<A NAME="RZ02307SS-8D">8d</A> Enders D. Palecek J. Grondal C. Chem. Commun.  2006,  655 

<A NAME="RZ02307SS-8E">8e</A> Enders D. Vrettou M. Synthesis  2006,  2155 

<A NAME="RZ02307SS-8F">8f</A> Enders D. Grondal C. Vrettou M. Synthesis  2006,  3597 

<A NAME="RZ02307SS-8G">8g</A> Enders D. Chow S. Eur. J. Org. Chem.  2006,  4578 

<A NAME="RZ02307SS-8H">8h</A> Enders D. Grondal C. Synlett  2006,  3507 

<A NAME="RZ02307SS-9">9</A>

(i) Enders, D.; Grondal, C. Adv. Synth. Catal., 2007, in press. For related publications, see:

(j) Westermann B. Neuhaus C. Angew. Chem. Int. Ed.  2005,  44:  4077 ; Angew. Chem. 2005, 117, 4145

(k) Suri JT. Ramachary DB. Barbas CF. Org. Lett.  2005,  7:  1383 

(l) Suri JT. Mitsumori S. Albertshofer K. Tanaka F. Barbas CF. J. Org. Chem.  2006,  71:  3822 

(m) Ibrahem I. Córdova A. Tetrahedron Lett.  2005,  46:  3363 

(n) Ibrahem I. Zou W. Casas J. Sundén H. Córdova A. Tetrahedron  2006,  62:  357 

(o) Ibrahem I. Zou W. Xu Y. Córdova A. Adv. Synth. Catal.  2006,  348:  211 

(p) Majewski M. Niewczas I. Palyam N. Synlett  2006,  2387 

For recent applications of the dioxanone method, see:

<A NAME="RZ02307SS-10A">10a</A> Enders D. Breuer I. Raabe G. Synthesis  2005,  3517 

<A NAME="RZ02307SS-10B">10b</A> Enders D. Hieronymi A. Ridder A. Synlett  2005,  2391 

<A NAME="RZ02307SS-10C">10c</A> Enders D. Breuer I. Drosdow E. Synthesis  2005,  3239 

<A NAME="RZ02307SS-10D">10d</A>

Enders, D.; Herriger, C. Eur. J. Org. Chem., 2007, 1085.

<A NAME="RZ02307SS-11">11</A> For a review, see: Enders D. Wortmann L. Peters R. Acc. Chem. Res.  2000,  33:  157 

<A NAME="RZ02307SS-12">12</A>

Crystallographic data have been deposited with the Cambridge Crystallographic Data Centre as supplementary publication no. CCDC 634702. Copies of the data can be obtained free of charge on application to CCDC, 12 Union Road, Cambridge CB2 1EZ, UK [fax: [phone],
e-mail: [e-mail], or www.ccdc.cam.ac.uk].

<A NAME="RZ02307SS-13">13</A> Enders D. Fey P. Kipphardt H. Org. Synth.  1987,  65:  173