RSS-Feed abonnieren
DOI: 10.1055/s-0030-1260311
Proximal Ester Assistance vs. Stereoelectronic Prohibition in Catalytic N-Acyliminium Ion Reactions: Stereoselective Formation of Aza-Heterocycles with Two Contiguous Quaternary-Tertiary Stereocenters
Publikationsverlauf
Publikationsdatum:
13. September 2011 (online)
![](https://www.thieme-connect.de/media/synlett/201116/lookinside/thumbnails/10.1055-s-0030-1260311-1.jpg)
Abstract
The catalytic intramolecular and intermolecular α-amidoalkylation of deactivated N,O-acetals equipped with either two ester groups or both an ester and a cyano groups α to the reactive center has been developed. Reactions in the cyano ester series proceeded under harsher reaction conditions than those in the diester series, but furnished products with two contiguous quaternary and tertiary stereocenters with high to complete diastereocontrol. The reactivity trends and stereoselectivity profiles exhibited by these reactions may be consistent with a relay mode exerted by the ester arm(s), which might possibly direct the catalyst delivery and/or stabilize the raising carbenium ion through anchimeric bridging.
Key words
catalysis - bistrifluoromethanesulfonimide - N-acyliminium - directing effect and relay mode - diastereocontrol
- Supporting Information for this article is available online:
- Supporting Information
-
1a For
authoritative reviews on N-acyliminium
ion chemistry, see:
Speckamp WN.Moolenaar MJ. Tetrahedron 2000, 56: 3817 -
1b
Maryanoff BE.Zhang H.-C.Cohen JH.Turchi IJ.Maryanoff CA. Chem. Rev. 2004, 104: 1431 - For two recent exhaustive reviews on the intermolecular amidoalkylation of N,O-acetals, see:
-
2a
Yazici A.Pyne SG. Synthesis 2009, 339 -
2b
Yazici A.Pyne SG. Synthesis 2009, 513 - 3
Pin F.Comesse S.Garrigues B.Marchalin Š.Daich A. J. Org. Chem. 2007, 72: 1181 -
4a
Ben Othman R.Bousquet T.Othman M.Dalla V. Org. Lett. 2005, 7: 5335 -
4b
Tranchant MJ.Moine C.Ben Othman R.Bousquet T.Othman M.Dalla V. Tetrahedron Lett. 2006, 47: 4477 - 5
Ben Othman R.Affani R.Tranchant MJ.Antoniotti S.Duñach E.Dalla V. Angew. Chem. Int. Ed. 2010, 49: 776 - For some other recent reports on catalytic amidoalkylation of N,O-acetals:
-
6a
Okitsu O.Suzuki R.Kobayashi S.
J. Org. Chem. 2001, 66: 809 -
6b
Camilo NS.Pilli RA. Tetrahedron Lett. 2004, 45: 2821 -
6c
de Godoy LAF.Camilo NS.Pilli RA. Tetrahedron Lett. 2006, 47: 7853 -
6d
Ben Othman R.Bousquet T.Fousse A.Othman M.Dalla V. Org. Lett. 2005, 7: 2825 ; and references therein -
6e
Kinderman SS.Wekking MMT.van Maarseveen JH.Schoemaker HE.Hiemstra H.Rutjes FPJT.
J. Org. Chem. 2005, 70: 5519 - For impressive catalytic enantioselective approaches, see:
-
7a
Raheem IT.Thiara PS.Peterson EA.Jacobsen EN. J. Am. Chem. Soc. 2007, 129: 13404 -
7b
Raheem IT.Thiara PS.Jacobsen EN. Org. Lett. 2008, 10: 1577 -
7c
Peterson EA.Jacobsen EN. Angew. Chem. Int. Ed. 2009, 48: 6328 -
7d
Muratore MC.Holloway CA.Pilling AW.Storer RI.Trevitt G.Dixon DJ. J. Am. Chem. Soc. 2009, 131: 10796 - 8
Moussa S.Comesse S.Dalla V.Daïch A.Sanselme M.Netchitaïlo P. Synlett 2010, 2197 -
9a
Grau F.Heumann A.Duñach E. Angew. Chem. Int. Ed. 2006, 45: 7285 -
9b
Paz Muñoz M.Lloyd-Jones GC. Eur. J. Org. Chem. 2009, 516 - For a recent series of papers reporting diastereoselective alkylation of chiral alcohol derivatives bearing an adjacent ester group, see:
-
10a
Rubenbauer P.Bach T. Adv. Synth. Catal. 2008, 350: 1125 -
10b
Stadler D.Bach T. J. Org. Chem. 2009, 74: 4747 -
10c
Rubenbauer P.Bach T. Chem. Commun. 2009, 2130 -
10d
Cozzi PG.Benfatti F. Angew. Chem. Int. Ed. 2010, 49: 256 - 11 For related studies in our group,
see:
Comesse S.Sanselme M.Daïch A. J. Org. Chem. 2008, 73: 5566 - 19 For a representative paper, see:
Louwrier S.Ostendorf M.Boom A.Hiemstra H.Speckamp WN. Tetrahedron 1996, 52: 2603
References and Notes
Typical Procedure
for the Preparation of 4a-d
To a solution
of an N,O-acetal 3a-d (0.4
mmol) in a freshly distilled solvent as indicated in Table
[¹]
(1.5 mL) was added dropwise
a 0.5 M CH2Cl2 solution of HNTf2 (40 µL,
0.02 mmol, 0.05 equiv). The reaction was stirred at the temper-ature
indicated in Table
[¹]
and
followed by TLC. At the end of the reaction, the solution was quenched
at r.t. by a 5% aq solution of NaHCO3, and the
aqueous phase was extracted two times with EtOAc (3 mL). The combined
organic layers were dried over MgSO4, the solvent was
removed under vacuum, and the residue was then purified by silica
gel chromatography to provide the desired tricycles 4a-d.
Physical
Data for 4b
Isolated as white solid (recrystallized
from Et2O); mp 157-159 ˚C;
yield 95% (EtOAc-cyclohexane, 40:60). IR (KBr): 1728,
1691 cm-¹. ¹H NMR
(300 MHz, CDCl3): δ = 0.84 (t, J = 7.0 Hz,
3 H), 1.36 (t, J = 7.0
Hz, 3 H), 2.60 (d, J = 16.4 Hz,
1 H), 2.79-3.03 (m, 3 H), 3.05 (d, J = 16.4
Hz, 1 H), 3.62-3.84 (m, 2 H), 3.84 (s, 6 H), 4.29-4.50
(m, 3 H), 5.54 (s, 1 H), 6.57 (s, 1 H), 7.30 (s, 1 H). ¹³C
NMR (75 MHz, CDCl3): δ = 13.7, 14.3,
28.6, 37.8, 40.1, 60.9, 62.0, 26.6, 110.8, 110.5, 123.6, 127.9,
147.7, 148.4, 168.9, 169.8, 170.7.
A simple steric bias (ester > cyano) could also be considered as an alternative or competitive mechanism, in line with ref. 10.
14Analytical data and copy of the ¹H NMR spectrum for compound 4d are provided in the Supporting Information.
15Full crystallographic data have been deposited at the Cambridge Crystallographic Data Centre; CCDC reference number 833548 for the major diastereoisomer of product 4d. Copies of the data can be obtained free of charge at the following address: http://www.ccdc.cam.ac.uk.
16For typical procedure for the preparation of 6-10, see the Supporting Information.
17When these allylations were performed at 60 ˚C overnight, around 25% conversion into the desired product was observed, thus confirming the importance of the two ester functions for an efficient process under mild conditions in the intermolecular reactions too.
18For typical procedure for the preparation of 12-15, see the Supporting Information.