Abstract
In contrast to amino acids with a bulky substituent like tert-leucine, adamantylglycine has so
far received little attention. Here, a new, practical synthesis
of adamantylglycine is described. This is based on a highly diastereoselective
addition of adamantyl Grignard reagent to 2,3-O-cyclohexylideneglyceraldehyde N-benzylnitrone, mediated by the Lewis
acid diethylaluminum chloride. Adamantylglycine is obtained from
the nitrone in 6 steps and 28% yield as a crystalline hydrochloride
with 0.5 methanol incorporated.
Key words
glyceraldehyde - chiral nitrone - Grignard
addition - electrophilic glycine equivalent - crystal
structure
References
For overviews with numerous examples
of applications, see:
1a
Risch N.
Arend M.
In Houben-Weyl, Methoden der
Organischen Chemie
4th ed., Vol. E21b:
Helmchen G.
Hoffmann RW.
Mulzer J.
Schaumann E.
Thieme;
Stuttgart:
1995.
p.1833
1b
Principles
and Applications of Asymmetric Synthesis
Lin G.-Q.
Li Y.-M.
Chan ASC.
Wiley-Interscience;
New
York:
2001.
1c
Asymmetric Synthesis
of Natural Products
Koskinen A.
Wiley;
Chichester:
1993.
1d
Asymmetric
Synthesis - The Essentials
Christmann M.
Bräse S.
Wiley-VCH;
Weinheim:
2007.
2a
Chemistry and Biochemistry of the Amino Acids
Barrett GC.
Chapman
and Hall;
London:
1985.
2b
Scott JW. In Asymmetric Synthesis
Vol.
4:
Morrison JD.
Scott JW.
Academic Press;
Orlando:
1984.
p.1
2c
Asymmetric
Synthesis: Construction of Chiral Molecules Using Amino Acids
Coppola GM.
Schuster HF.
Wiley;
New York:
1987.
3a
Chiral Auxiliaries and Ligands in Asymmetric
Synthesis
Seyden-Penne J.
Wiley;
New
York:
1995.
3b
Evans DA. In Asymmetric Synthesis
Vol.
3B:
Morrison JD.
Academic
Press;
Orlando:
1984.
p.1
3c
Meyers AI.
Lutomski KA. In Asymmetric Synthesis
Vol.
3B:
Morrison JD.
Academic
Press;
Orlando:
1984.
p.213
3d
Enders D. In Asymmetric Synthesis
Vol.
3B:
Morrison JD.
Academic
Press;
Orlando:
1984.
p.275
3e
Job A.
Janeck CF.
Bettray W.
Peters R.
Enders D.
Tetrahedron:
Asymmetry
2002,
58:
2253
4a
Kagan HB. In Asymmetric
Synthesis
Vol. 5:
Morrison JD.
Academic Press;
Orlando:
1985.
p.1
4b
Wang
D.-H.
Engle KM.
Shi B.-F.
Yu JQ.
Science
2010,
327:
315
See, e.g.:
5a
Longbottom DA.
Franckevicius V.
Ley SV.
Chimia
2007,
61:
247
5b
Seayad J.
List B.
Org. Biomol. Chem.
2005,
3:
719
For uses of tert-leucine
and tert-leucinol, see:
6a
Tomioka K.
Koga K. In Asymmetric
Synthesis
Vol. 2A:
Morrison JD.
Academic Press;
New York:
1983.
p.201
6b
Guével A.-C. In
Encyclopedia of Reagents for Organic Synthesis
Vol.
5:
Paquette LA.
Wiley;
Chichester:
1995.
p.2961
6c
Bolm C.
Kasyan A.
Drauz K.
Günther K.
Raabe G.
Angew. Chem.
Int. Ed.
2000,
39:
2288 ; Angew. Chem. 2000, 112, 2374 (including references to tert-sila-leucine)
7
Mahadik GS.
Hitchcock SR.
Tetrahedron: Asymmetry
2010,
21:
33
8a
Do KQ.
Tanei P.
Gavierel M.
Schwyzer R.
Helv. Chim.
Acta
1979,
62:
956
8b
Belokon YN.
Maleyev VI.
Vitt SV.
Ryzhov MG.
Kondrashov YD.
Golubev SN.
Vauchskii YP.
Kazika AI.
Novikova MI.
Krasutski PA.
Yurchenko AG.
Dubchak IL.
Shklover VE.
Struchkov YT.
Bakhmutov VI.
Belikov VM.
J. Chem. Soc., Dalton Trans.
1985,
17
8c
Gálvez N.
Moreno-Mañas M.
Vallribera A.
Molins E.
Cabrero A.
Tetrahedron Lett.
1996,
37:
6197
8d
Gálvez N.
Moreno-Mañas M.
Padros I.
Sebastian RM.
Serra N.
Vallribera A.
Polyhedron
1995,
14:
1397
8e
Clariana J.
Garsía-Granda S.
Gotor V.
Gutiérrez-Fernández A.
Luna A.
Moreno-Mañas M.
Vallribera A.
Tetrahedron: Asymmetry
2000,
11:
4549
8f
Augeri DJ.
Robl JA.
Betebenner DA.
Magnin DR.
Khanna A.
Robertson JG.
Wang A.
Simpkins LA.
Taunk P.
Huang Q.
Han S.-P.
Abboa-Offei B.
Cap M.
Xin L.
Tao L.
Tozzo E.
Welzel GE.
Egan DM.
Marcinkeviciene J.
Chang SY.
Biller SA.
Kirby MS.
Parker RA.
Hamann LG.
J.
Med. Chem.
2005,
48:
5025
9 Yield of 1˙HCl
2.3% after 6 steps from 1-adamantane carboxaldehyde: Hasegawa M.
Taniyama D.
Tomioka K.
Tetrahedron
2000,
56:
10153
10 cf.: Use of adamantylglycinol for
respective oxazoline ligands: Villhauer EB.
Brinkman JA.
Naderi GB.
Burkey BF.
Dunning BE.
Prasad K.
Mangold BL.
Russell ME.
Hughes TE.
J. Med. Chem.
2003,
46:
2774
11
Wanka L.
Cabrele C.
Vanejews M.
Schreiner PR.
Eur. J. Org. Chem.
2007,
1474
12
Aldrich PE.
Hermann EC.
Meier WE.
Paulshock M.
Prichard WW.
Snyder JA.
Watts JC.
J. Med. Chem.
1971,
14:
535
13
Rosenthal K.
Sokol MS.
Ingram RL.
Subramanian R.
Fort RC.
Antimicrob. Agents Chemother.
1982,
22:
1031
For pioneering work concerning
RM additions to 2,3-O-isopropylidene
gylceraldehyde imines, see:
14a
Yoshimura J.
Sato T.
J. Am. Chem. Soc.
1964,
86:
3858
14b
Ohgo Y.
Yoshimura J.
Sato T.
Bull.
Chem. Soc. Jpn.
1969,
42:
728
14c See also: Carcano M.
Nicotra F.
Panza L.
Russo G.
Chem. Commun.
1989,
297
15
Bloch R.
Chem.
Rev.
1998,
98:
1407
16
Franz T.
Hein M.
Veith U.
Jäger V.
Peters E.-M.
Peters K.
von Schnering HG.
Angew.
Chem., Int. Ed. Engl.
1994,
33:
1298 ; Angew. Chem. 1994, 106, 1308
17a
Veith U.
Leurs S.
Jäger V.
Chem. Commun.
1996,
329
17b
Meunier N.
Veith U.
Jäger V.
Chem.
Commun.
1996,
331
18a
Veith U.
Schwardt O.
Jäger V.
Synlett
1996,
1181
18b
Schwardt O.
Veith U.
Gaspard C.
Jäger V.
Synthesis
1999,
1473
19
Li F.
Schwardt O.
Jäger V.
Synthesis
2006,
2173 ; and references cited therein
For basic work on such nitrone
additions, see:
20a
Dondoni A.
Franco S.
Merchan FL.
Merino P.
Tejero T.
Tetrahedron
Lett.
1993,
34:
5475
20b
Merino P.
Castillo E.
Merchan FL.
Tejero T.
Tetrahedron: Asymmetry
1997,
8:
1725
20c
Merino P.
Anoro S.
Castillo E.
Merchan F.
Tejero T.
Tetrahedron:
Asymmetry
1996,
7:
1887
20d
Merino P.
Castillo E.
Franco S.
Merchan FL.
Tejero T.
Tetrahedron
1998,
54:
12301
20e
Merino P.
Castillo E.
Franco S.
Merchan FL.
Tejero T.
J.
Org. Chem.
1998,
63:
2371
20f
Schade W.
Reissig H.-U.
Synlett
1999,
632
20g
Merino P.
C.
R. Chim.
2005,
8:
775
20h cf.: Portolés R.
Murga J.
Falomir E.
Carda M.
Uriel S.
Marco JA.
Synlett
2002,
711
21a
Li F.
Ph.D. Dissertation
University
of Stuttgart;
Germany:
2007.
21b cf.: Jäger V.
Bierer L.
Dong H.-Q.
Palmer A.
Shaw D.
Frey W.
J. Heterocycl. Chem.
2000,
37:
455
21c
Palmer AM.
Jäger V.
Synlett
2000,
1405
21d
Palmer AM.
Jäger V.
Eur.
J. Org. Chem.
2001,
1293
21e
Palmer AM.
Jäger V.
Eur.
J. Org. Chem.
2001,
2547
22 For ‘asymmetric derivatization
of glycines’ and ‘glycine cations’, see: Williams RM.
Synthesis
of Optically Active α-Amino Acids
Pergamon
Press;
Oxford:
1989.
p.95
23
Methods
for the Oxidation of Organic Compounds
Haines AH.
Academic Press;
London:
1988.
24a
Zimmermann PJ.
Blanarikova I.
Jäger V.
Angew. Chem.
Int. Ed.
2000,
39:
910 , Angew. Chem. 2000, 112, 936
24b
Zimmermann PJ.
Lee J.-Y.
Blanarikova I.
Endermann R.
Häbich D.
Jäger V.
Eur.
J. Org. Chem.
2005,
3450
24c
Lee J.-Y.
Schiffer G.
Jäger V.
Org.
Lett.
2005,
7:
2317
24d
Henneböhle M.
Le Roy P.-Y.
Hein M.
Ehrler R.
Jäger V.
Z. Naturforsch., B
2004,
59:
451
25a
Hubschwerlen C.
Schmid G.
Helv.
Chim. Acta
1993,
66:
2206
25b
Hubschwerlen C.
Synthesis
1986,
962
25c
Krämer B.
Franz T.
Picasso S.
Pruschek P.
Jäger V.
Synlett
1997,
295
25d
Palomo C.
Aizpurua JM.
García JM.
Galarza R.
Legido M.
Urchegui R.
Román P.
Luque A.
Server-Carrió J.
Linden A.
J. Org. Chem.
1997,
62:
2070
26
Yurchenko AG.
Fedorenko TV.
Zh. Org. Khim.
1987,
23:
970 ; Chem. Abstr. 1988, 108, 204255y
27
Dondoni A.
Franco S.
Junquera F.
Merchan F.
Merino P.
Tejero T.
Synth. Commun.
1994,
24:
2537
28 cf.: Use in isoxazolidine reductions: DeShong P.
Dicken CM.
Leginus JM.
Whittle RR.
J. Am. Chem. Soc.
1984,
106:
5598
29
Rundel W. In Houben-Weyl, Methoden der Organischen Chemie
4th
ed., Vol. X/4:
Müller E.
Thieme;
Stuttgart:
1968.
p.309
30
Frey W.
Baskakova A.
Jäger V.
Z.
Kristallogr. - New Cryst. Struct.
2009,
224:
27
31a
Yin H.
Franck RW.
Chen S.-L.
Quigley GJ.
Todardo L.
J. Org. Chem.
1992,
57:
644
31b
Menzel A.
Ph.D. Dissertation
University
of Stuttgart;
Germany:
2000.
32
Kocienski PJ.
Protecting Groups
Thieme;
Stuttgart:
1994.
p.95
33
Frey W.
Baskakova A.
Menzel A.
Jäger V.
Z. Kristallogr. - New
Cryst. Struct.
2010,
225:
245
34
Frey W.
Baskakova A.
Jäger V.
Z.
Kristallogr. - New Cryst. Struct.
2010,
225:
247
35a
Kraus GA.
Roth B.
J.
Org. Chem.
1980,
45:
4825
35b
Lindgren BO.
Hilsson T.
Acta Chem.
Scand.
1973,
27:
888
36 Crystallographic data for adamantylglycine 1˙HCl˙(0.5MeOH) have
been deposited with the Cambridge Crystallographic Data Centre as
supplementary publication no. CCDC-770794. Copies of the data can
be obtained, free of charge, on application to CCDC, 12 Union Road, Cambridge
CB2 1EZ, UK [fax: +44 (1223)336033 or e-mail:
deposit@ccdc.cam.ac.uk].
37 The presence of MeOH in crystalline 1˙HCl has apparently been overlooked
in earlier work.8,9
38
Liu K.-C.
Shelton BR.
Howe RK.
J. Org. Chem.
1980,
45:
3916
39a
Maskill H.
Jencks WP.
J.
Am. Chem. Soc.
1987,
109:
2062
39b
Borch RF.
Bernstein MD.
Durst HD.
J. Am. Chem. Soc.
1971,
93:
2897
40a
Schmid CR.
Bryant JD.
Dowlatzedah M.
Philips JL.
Prather DE.
Schantz RD.
Sear NL.
Vianco CS.
J.
Org. Chem.
1991,
56:
4056
40b
Chittenden GJF.
Carbohydr. Res.
1980,
84:
350
41a
Sheldrick GM.
SHELXS-97.
Program for the Solution of Crystal Structures
University
of Göttingen;
Germany:
1997.
41b
Sheldrick GM.
SHELXL-97. Program for
the Refinement of Crystal Structures
University
of Göttingen;
Germany:
1997.
41c
Sheldrick GM.
SHELXTL-Plus. Structure
Determination Software Suite
Release 4.1. Siemens
Analytical Systems Inc.;
Madison:
1991.
42 cf.: Veith U.
Diploma Thesis
University
of Würzburg;
Germany:
1991.
43
Canas-Rodriguez A.
Ruiz-Poveda SG.
Coronel-Borges LA.
Carbohydr. Res.
1987,
159:
217
44
Basel Y.
Hassner A.
J. Org. Chem.
2000,
65:
6368
