Abstract
Aldol reactions of racemic enolizable dioxolan-protected α-substituted-β-ketoaldehydes
with representative achiral ketones catalyzed by proline or 5-(2-pyrrolidine-2-yl)-1H -tetrazole in wet DMSO proceed with
dynamic kinetic resolution (or via DYKAT with an α-substituted-β-alkoxyaldehyde)
to give adducts with high dr and ee.
Key words
aldol reaction - chiral aldehydes - kinetic
resolution - organocatalysis - polypropionates
References
<A NAME="RY02310ST-1">1 </A>
List B.
Lerner RA.
Barbas CF.
J.
Am. Chem. Soc.
2000,
122:
2395
2a </A>
Zlotin SG.
Kucherenko AS.
Beletskaya IP.
Russ. Chem. Rev.
2009,
78:
737
2b </A>
Kotsuki H.
Ikishima H.
Okuyama A.
Heterocycles
2008,
75:
493
2c </A>
Melchiorre P.
Marigo M.
Carlone A.
Bartoli G.
Angew. Chem. Int. Ed.
2008,
47:
6138
2d </A>
Mukherjee S.
Yang JW.
Hoffmann S.
List B.
Chem. Rev.
2007,
107:
5471
2e </A>
Pellissier H.
Tetrahedron
2007,
63:
9267
2f </A>
Guillena G.
Najera C.
Ramon DJ.
Tetrahedron:
Asymmetry
2007,
18:
2249
3a </A>
Ward DE.
Man CC.
Guo C.
Tetrahedron Lett.
1997,
38:
2201
3b </A>
Ward DE.
Guo C.
Sasmal PK.
Man
CC.
Sales M.
Org. Lett.
2000,
2:
1325
3c </A>
Ward DE.
Becerril-Jimenez F.
Zahedi MM.
J. Org. Chem.
2009,
74:
4447 ; and references cited therein
4a </A>
Ward DE.
Jheengut V.
Tetrahedron
Lett.
2004,
45:
8347
4b </A>
Nyberg AI.
Usano A.
Pihko PM.
Synlett
2004,
1891
4c </A>
Pihko PM.
Laurikainen KM.
Usano A.
Nyberg AI.
Kaavi JA.
Tetrahedron
2006,
62:
317
5a </A>
Hanessian S.
Mi X.
Synlett
2010,
761
5b </A>
Suri JT.
Ramachary DB.
Barbas CF.
Org. Lett.
2005,
7:
1383
5c </A>
Palyam N.
Majewski M.
J. Org. Chem.
2009,
74:
4390
5d </A>
Calderon F.
Doyaguez EG.
Cheong PH.-Y.
Fernandez-Mayoralas A.
Houk KN.
J. Org. Chem.
2008,
73:
7916
5e </A>
Ibrahem I.
Zou W.
Xu Y.
Cordova A.
Adv. Synth. Catal.
2006,
348:
211
5f </A>
Grondal C.
Enders D.
Tetrahedron
2006,
62:
329
5g </A>
Alcaide B.
Almendros P.
Luna A.
Torres MR.
J. Org. Chem.
2006,
71:
4818
5h </A>
Cordova A.
Ibrahem I.
Casas J.
Sunden H.
Engqvist M.
Reyes E.
Chem. Eur. J.
2005,
11:
4772
5i </A>
Chercheja S.
Nadakudity SK.
Eilbracht P.
Adv.
Synth. Catal.
2010,
352:
637
5j </A>
Reyes E.
Cordova A.
Tetrahedron Lett.
2005,
46:
6605
5k </A>
Wang Y.
Zhang Y.
Chin. J. Chem.
2010,
28:
1267
5l </A>
Yang J.
Wang T.
Ding Z.
Shen Z.
Zhang Y.
Org. Biomol.
Chem.
2009,
7:
2208
5m </A>
Wang Y.
Shen Z.
Li B.
Zhang Y.
Zhang Y.
Chem. Commun.
2007,
1284 ; for citations to early examples, see ref.
8a
<A NAME="RY02310ST-6">6 </A> Kinetic resolution of racemic substrates
is equivalent to an enantiotopic-group-selective reaction, i.e.,
groups on enantiomeric substrates are enantiotopic by external comparison.
See:
Mislow K.
Raban M.
Top.
Stereochem.
1967,
1:
1
7a </A>
Masamune S.
Choy W.
Petersen JS.
Sita LR.
Angew. Chem., Int. Ed. Engl.
1985,
24:
1
7b </A>
Kolodiazhnyi OI.
Tetrahedron
2003,
59:
5953
8a </A>
Ward DE.
Jheengut V.
Akinnusi OT.
Org. Lett.
2005,
7:
1181
8b </A>
Ward DE.
Jheengut V.
Beye GE.
<A NAME="RY02310ST-9">9 </A>
Pellissier H.
Tetrahedron
2008,
64:
1563
<A NAME="RY02310ST-10">10 </A> Review:
Longbottom DA.
Franckevicius V.
Kumarn S.
Oelke AJ.
Wascholowski V.
Ley SV.
Aldrichimica Acta
2008,
41:
3
<A NAME="RY02310ST-11">11 </A>
Little or no aldol adducts were observed
in CHCl3 , MeCN, or THF.
<A NAME="RY02310ST-12">12 </A>
A solution of 5c (2
M in DMF), H2 O (1 equiv), and 6 (0.2 equiv)
at r.t. for 2 d gave a 1:1.1 mixture (by ¹ H
NMR) of 2c and 5c (46% isolated;
dr = 20, ee >95%).
<A NAME="RY02310ST-13">13 </A>
A DMSO solution of (-)-5a , H2 O (8 equiv), and 6 (0.2 equiv) at r.t. for 4 d gave a 1:1.8
mixture (by ¹ H NMR) of (±)-2a and (-)-5a (43% isolated;
dr >20, ee >95%).
<A NAME="RY02310ST-14">14 </A>
After 2 d, a solution of (±)-2b in DMSO containing D2 O 4 or 6 (0.5
equiv) showed >90% deuteration of the α-CH
confirming racemization under these conditions.
<A NAME="RY02310ST-15">15 </A>
We were unable to determine the ee
for 13a .
<A NAME="RY02310ST-16">16 </A>
Subjecting 11a or 11b to the reaction conditions confirmed their
susceptibility to elimination, particularly in the presence of 6 .
<A NAME="RY02310ST-17">17 </A>
Ward DE.
Sales M.
Man CC.
Shen J.
Sasmal PK.
Guo C.
J. Org. Chem.
2002,
67:
1618
18a </A>
Steinreiber J.
Faber K.
Griengl H.
Chem. Eur.
J.
2008,
14:
8060
18b </A>
Yamaguchi A.
Matsunaga S.
Shibasaki M.
J.
Am. Chem. Soc.
2009,
131:
10842
18c </A>
Steinreiber J.
Schurmann M.
Wolberg M.
van Assema F.
Reisinger C.
Fesko K.
Mink D.
Griengl H.
Angew. Chem. Int. Ed.
2007,
46:
1624
19a </A>
Evans DA.
Dart MJ.
Duffy JL.
Rieger DL.
19b </A>
Evans DA.
Dart MJ.
Duffy JL.
Yang MG.
J.
Am. Chem. Soc.
1996,
118:
4322
20 </A>
We were unable to determine the ee
for 17 . ¹ H NMR of the crude
product suggested the possible presence of minor amounts of other
adducts arising from 14 but these could
not be quantified or isolated. The maximum yield of enantiopure 18 from this reaction is 50%.
21a </A>
Beye GE.
Ward DE.
J.
Am. Chem. Soc.
2010,
132:
7210
21b </A>
Jheengut V.
Ward DE.
J. Org. Chem.
2007,
72:
7805
<A NAME="RY02310ST-22">22 </A> Compound (±)-5a is also a useful intermediate:
Ward DE.
Gillis HM.
Akinnusi OT.
Rasheed MA.
Saravanan K.
Sasmal PK.
Org. Lett.
2006,
8:
2631
23a </A>
Izquierdo I.
Plaza MT.
Robles R.
Mota AJ.
Franco F.
Tetrahedron: Asymmetry
2001,
12:
2749
23b </A>
Shigehisa H.
Mizutani T.
Tosaki S.-Y.
Ohshima T.
Shibasaki M.
Tetrahedron
2005,
61:
5057
<A NAME="RY02310ST-24">24 </A>
Rodriguez B.
Bruckmann A.
Bolm C.
Chem.
Eur. J.
2007,
13:
4710
<A NAME="RY02310ST-25">25 </A>
The mixture is initially homogeneous
but becomes solid as 5a precipitates. Diastereoselectivity
was improved with small amounts of water (2 equiv, dr >20;
0 equiv, dr = 13) but the reaction was
suppressed with larger amounts (ref. 4).
<A NAME="RY02310ST-26">26 </A>
Presumably by increasing the solubility
of 6 and increasing the rate of racemization
of 2a .
