Abstract
Conjugate additions of reactive organolithium compounds such
as phenyllithium, n -butyllithium, tert -butyllithium, and 2-propenyllithium
to 6H -1,2-oxazines 1 , 24 , and 25 followed by
trapping of the intermediates with electrophiles gave a variety
of highly substituted 6-alkoxy-5,6-dihydro-4H -1,2-oxazines 2 -15 and 27 -30 generally
in very good yields. Most interestingly, this reaction sequence
proceeds with high stereocontrol producing in large excess or exclusively
the trans,trans -diastereomers. Using
benzaldehyde as the electrophile, only compound 8 ,
which is one of eight possible diastereomers, was formed. Methyllithium
or lithiated methoxyallene as the nucleophilic component provide
expected addition products 17 and 19 , but formation of bis-1,2-oxazines 18 and 20 seems
to be inevitable with these less reactive organolithium compounds.
Key Words
asymmetric synthesis - conjugate addition - organolithium
compounds - 1,2-oxazines - alkylation
References
1a </A>
Chrystal EJT.
Gilchrist TL.
Stretch W.
J.
Chem. Res., Synop.
1987,
180
1b </A>
Chrystal EJT.
Gilchrist TL.
Stretch W.
J. Chem. Res., Miniprint
1987,
1563
<A NAME="RT02802SS-2">2 </A>
Henning R.
Lerch U.
Urbach H.
Synthesis
1989,
265
<A NAME="RT02802SS-3">3 </A>
Hippeli C.
Reissig H.-U.
Liebigs Ann. Chem.
1990,
475
<A NAME="RT02802SS-4">4 </A>
Zimmer R.
Hoffmann M.
Reissig H.-U.
Chem.
Ber.
1992,
125:
2243
<A NAME="RT02802SS-5">5 </A>
Angermann J.
Homann K.
Reissig H.-U.
Zimmer R.
Synlett
1995,
1014
<A NAME="RT02802SS-6">6 </A>
Zimmer R.
Angermann J.
Hain U.
Hiller F.
Reissig H.-U.
Synthesis
1997,
1467
<A NAME="RT02802SS-7">7 </A>
Zimmer R.
Homann K.
Angermann J.
Reissig H.-U.
Synthesis
1999,
1223
<A NAME="RT02802SS-8">8 </A>
Homann K.
Dissertation
Technische
Hochschule;
Darmstadt:
1994.
<A NAME="RT02802SS-9">9 </A>
Angermann J.
Dissertation
Technische
Universität;
Dresden:
1997.
<A NAME="RT02802SS-10">10 </A>
Homann K.
Angermann J.
Collas M.
Zimmer R.
Reissig H.-U.
J.
Prakt. Chem.
1998,
340:
649
<A NAME="RT02802SS-11">11 </A>
Schmidt E.
Dissertation
Technische
Universität;
Dresden:
2001.
<A NAME="RT02802SS-12">12 </A>
Zimmer R.
Hiller F.
Reissig H.-U.
Heterocycles
1999,
50:
393
<A NAME="RT02802SS-13">13 </A>
Hartl H.
Brüdgam I.
Reissig H.-U.
Buchholz M.
Z. Kristallogr.
2001,
216:
591
<A NAME="RT02802SS-14">14 </A>
Paulini K.
Gerold A.
Reissig H.-U.
Liebigs
Ann. Chem.
1995,
667
<A NAME="RT02802SS-15">15 </A>
Mander LN.
Sethi SP.
Tetrahedron Lett.
1983,
24:
5425
<A NAME="RT02802SS-16">16 </A>
Winn M.
von Geldern TW.
Opgenorth TJ.
Jae H.
Tasker AS.
Boyd SA.
Kester JA.
Mantei RA.
Bal R.
Sorensen BK.
Wu-Wong JR.
Chiou WJ.
Dixon DB.
Novosad EI.
Hernandez L.
Marsh KC.
J. Med. Chem.
1996,
39:
1039
<A NAME="RT02802SS-17">17 </A> For a review see:
Zimmer R.
Synthesis
1993,
165
<A NAME="RT02802SS-18">18 </A> For experimental and theoretical
investigations on regioselective additions of organolithium compounds
to α,β-unsaturated imines see:
Tomioka K.
Shioya Y.
Nagaoka Y.
Ymada K.
J. Org. Chem.
2001,
66:
7051 ; and references cited therein
<A NAME="RT02802SS-19">19 </A>
Buchholz, M.; Hiller, F.; Reissig,
H.-U. Eur. J. Org. Chem., in press.
<A NAME="RT02802SS-20">20 </A>
Trost BM.
Jungheim LN.
J. Am. Chem. Soc.
1980,
102:
7910
<A NAME="RT02802SS-21">21 </A>
Paquette LA.
Kuo LH.
Tae J.
J.
Org. Chem.
1998,
63:
2010
<A NAME="RT02802SS-22">22 </A>
Reissig H.-U.
Hippeli C.
Arnold T.
Chem.
Ber.
1990,
123:
2403
<A NAME="RT02802SS-23">23 </A>
Zimmer R.
Homann K.
Reissig H.-U.
Liebigs
Ann. Chem.
1993,
1155
