Stereoselective One-Pot synthesis of 1-Aminoindanes and 5,6-Fused azacycles using a Gold-Catalyzed Redox-Pinacol-Mannich-Michael cascade

Article abstract of DOI:10.1002/anie.200906346

"Chemical Equation Presented" Just another Mannich Monday: A cascade intramolecular redox-pinacol-Mannich-Michael reaction sequence catalyzed by gold complexes can be used to generate a variety of structures including spirocycles, 1-aminoindanes, and 5,6-fused azabicycles that have a quaternary carbon center. The reaction is characterized by complete atom-economy, high diastereoselectivity, and remarkable efficiency through tandem reactions.

Full text of DOI:10.1002/anie.200906346

Angewandte
Chemie
DOI: 10.1002/anie.200906346
Domino Reactions
Stereoselective One-Pot Synthesis of 1-Aminoindanes and 5,6-Fused
Azacycles Using a Gold-Catalyzed Redox-Pinacol-Mannich-Michael
Cascade**
Hyun-Suk Yeom, Youngun Lee, Jaewon Jeong, Eunsoo So, Soojin Hwang, Ji-Eun Lee,
Shim Sung Lee, and Seunghoon Shin*
Dedicated to Professor T. V. RajanBabu on the occasion of his 60th birthday
One way to improve the synthetic efficiency of the redox
reaction is to couple the reduction/oxidation steps with the
desired skeletal bond formations.[1] This strategy removes the
need for extra steps for the generation or protection of
reactive functional groups, or for oxidation state adjustment.
However, this requires that the redox precursors are more
readily available than, and able to be catalytically trans-
formed in situ into, their functional group counterparts that
undergo the desired transformation.[2] Recently, a number of
gold-catalyzed redox-exchange procedures via oxygen trans-
fer have been reported. For example, Toste and co-workers
and Zhang and co-workers reported sulfoxide-mediated or
amine-N-oxide-mediated redox reactions to generate carbene
rings motif with a quaternary center is often also found in
natural products or pharmaceutical agents, such as
NSC 344505, meloscine, and scandine.[8] The synthetic chal-
lenge of these target compounds continues to inspire creative
reaction design that allows for their efficient synthesis
through a rapid increase in molecular complexity.
We envisioned that metal carbenoid A,[6,9] generated from
the redox reaction of a readily available 38-alcohol precursor
(1), could be transformed into metal enolate B through a 1,2-
alkyl (pinacol) shift (Scheme 1).[10–11] With the selective
2
3
À
equivalents for sp or sp C H functionalization or 1,2-pinacol
shifts.[3–5] Furthermore, we have reported the waste-free
generation of azomethine ylide from an intramolecular
redox reaction between a nitrone and an alkyne.[6] The
unique advantage of using nitrones as oxidants is that they are
derived from readily available hydroxylamines and therefore
do not require stoichiometric oxidants such as mCPBA (meta-
chloroperbenzoicacid) or H2O2 for the substrate prepara-
tion.[4] Furthermore, two highly versatile intermediates,
namely an imine or a metal carbenoid, could be generated
in situ, which can be advantageously utilized in the rapid
assembly of pharmaceutically important N heterocycles
through cascade reactions.
We focused on the 1-aminoindane framework, which is a
common core of medicinal agents with various activities, such
as CB2 agonists, NMDA receptor agonists, and inhibition of
neuronal monoamine re-uptake.[7] The 5,6-fused piperidine
Scheme 1. The proposed redox-pinacol-Mannich-Michael cascade reac-
tion.
migration between the two alkyl group (R1 and R2) secured,
it should be possible to incorporate a variety of alkyl groups
(R1) at the quaternary position of b-amino cyclopentanone 2
using Mannich addition. Notably, if the nonmigrating group
(R2) is a vinyl group, the initially formed a,b-unsaturated
carbonyl compound would undergo a spontaneous Michael
reaction to afford synthetically useful 5,6-fused azabicycles in
a single operation. Herein, we report our preliminary results
on the assembly of these skeletons using a gold-catalyzed
redox cascade process.
[*] H.-S. Yeom, Y. Lee, J. Jeong, E. So, S. Hwang, Prof. Dr. S. Shin
Department of Chemistry and Research Institute for Natural
Sciences, Hanyang University
Seoul 133-791 (Korea)
Fax: (+82)2-2299-0762
E-mail: sshin@hanyang.ac.kr
Dr. J.-E. Lee, Prof. Dr. S. S. Lee
Department of Chemistry, Gyeongsang National University
Chinju 660-701 (Korea)
[**] This work was supported by the National Research Foundation of
Korea (KRF-2009-000-0000-0803). H.S.Y., Y.L., J.J., and E.S. thank
the BK21 program for the financial support. H.S.Y. also thanks the
Seoul Science Foundation for a fellowship.
We first inspected the viability of the redox-pinacol-
Mannich cascade reaction on 38-alcohol substrates that were
derived from cycloalkanones. After a brief examination of the
reaction conditions, we found that treating 1b with AuCl3
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/anie.200906346.
Angew. Chem. Int. Ed. 2010, 49, 1611 –1614
ꢀ 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
1611

Communications
Table 1: Spirocycle synthesis by a ring-expansion/Mannich reaction
(5 mol%) in nitromethane gave the desired spirocyclic b-
amino diketone 2b in 82% yield (determined by H NMR
sequence.[a]
1
spectroscopy) after only 10 minutes at room temperature
[Eq. (1)]. Gold(I) salts containing various ligands typically
took a longer reaction time and afforded diminished yields of
the product. However, PtCl2, Cu(OTf), Cu(OTf)2, and TfOH
(each at 5% loading), turned out to be inactive.[12] Notably, we
Entry
Substrate
Conditions
Yield of
1
only observed a single diastereomer of 2b in the H NMR
2 [%] (d.r.)[b]
spectrum of the crude mixture (d.r. > 20:1). The relative
stereochemistry of the related 2e was unambiguously con-
firmed by X-ray crystallography (see the Supporting Infor-
mation, Figure S1),[13] and the preference for the observed
diastereomer could be rationalized by the gold-chelated cyclic
transition state [Eq. (1)].
1
2
3
4
5
6
7
8
9
1a, X=H, n=0
1b, X=H, n=1
1c, X=H, n=2
1d, X=H, n=3
1e, X=4-Me, n=1
1 f, X=5-MeO, n=1
1g, X=5-F, n=1
1h, X=H, n=1, N-Ph
1i, X=H, n=1, N-Ar
(Ar=p-CO2MeC6H4)
RT, 1 h
RT, 1 h
69
78
58 (10:1)
76 (2:1)
83
87
84
74
68
508C, 0.5 h[c]
708C, 0.5 h[c]
RT, 0.5 h
RT, 1.5 h
RT, 1 h
RT, 1.5 h
RT, 1.5 h
10
11
RT, 1 h
67
RT, 1.5 h
69 (3:1)
Encouraged by this, we extended the procedure to
synthesize 5–8 membered spirocycles; Table 1, entries 1–4).
Using only 2 mol% of AuCl3, almost all spirocycles formed
efficiently at room temperature in less than 2 hours with
exceptional selectivity, although harsher conditions were
required for the larger rings, which formed with lower
diastereoselectivities, presumably owing to transannular ring
strain (Table 1, entries 3 and 4). Electronic effects on the
aromatic core did not make a marked difference to the
efficiency of this redox cascade (Table 1, entries 5–7) nor did
the electronic demands of the N substituent (Table 1,
entries 8 and 9). Alkyl/alkenyl-bridged substrates 1j–l also
reacted successfully under these condition (Table 1,
entries 10–12). Gratifyingly, this cascade reaction was suc-
cessfully extended to nitrone substrates that have an enoliz-
able a center, such as 1m and 1n. Substrates 1m–n reacted
smoothly with N-Ph nitrone, although the diastereoselectivity
relative to the existing center was modest (Table 1, entries 13
and 14).
12
508C, 0.5 h
78
70
13
14
RT, 0.5 h
RT, 0.5 h
(1.7:1)[d]
70
(1.6:1)[d]
[a] [1]=0.1m in CH3NO2. [b] Yield of isolated product (diastereomeric
ratio in parentheses; isolated as a single diastereomer unless otherwise
noted). [c] 5 mol% catalyst. [d] Diastereoselectivity relative to the center
a to the nitrone. Bn=benzyl.
of the migrating alkyl group, in the order Me > Et > iPr (as
shown by the formation of 2p/2p’, and 2q), which indicates
that it is a concerted 1,2-shift that goes through a sterically
congested transition state. Notably, aryl,[15c] alkynyl,[15d] and
alkenyl[15c] groups migrated preferentially over methyl group
in acyclic substrates 1r–t in a highly diastereoselective
manner, as shown in the preferential formation of 2r, 2s,
and 2t.[16,17]
In principle, the selective migration of R1 or R2 groups in 1
would allow for the incorporation of various moieties at the
quaternary position, which would lead to the aforementioned
product diversity (Scheme 1). Therefore, we examined the
selective 1,2-pinacol shift of various groups from tertiary
alcohol substrates with different R1 and R2 functionalities
(Table 2). The reaction of acyclic gem-dimethyl substrate 1o
with 2 mol% of AuCl3 indicated that the diastereomeric ratio
of the product is highly dependent on the reaction medium
(3:1 in CH3NO2 versus 14:1 in CH2Cl2); therefore, we chose
dichloromethane as the preferred solvent for acyclic sub-
strates in our investigation (Table 2).[14] The relative migra-
tion tendency of the 1,2-shift also depends on the steric bulk
Interestingly, when the nonmigrating group (R2) is a vinyl
group, the initially formed products (2) spontaneously
cyclized via a tandem Michael addition. For example, treat-
ment of divinyl substrate 1u with AuCl3 (2 mol%) in
dichloromethane at room temperature for 20 mininutes
gave the corresponding Michael adduct 3u, that has a vinyl
1612
www.angewandte.org
ꢀ 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Angew. Chem. Int. Ed. 2010, 49, 1611 –1614

Angewandte
Chemie
Table 2: Selective 1,2-shift and tandem Michael addition.[a,b]
various other useful compounds [Eq. (2) and Eq. (3)]. For
example, when 6–8 membered spirocyclic 1-aminoindanes
2b–d were treated with K2CO3 in methanol, 8–10 membered
medium-sized lactams 4b–d were obtained in 77–80% yield
through a trans-acylation process [Eq. (2)]. When a diaste-
reomeric mixture of 2o (d.r. 3:1) was initially acylated with
acryloyl chloride, then treated in situ with K2CO3 in MeOH
solution, 5,6-fused azacycle 5 (80% yield) was obtained as a
single diastereomer through the deacetylation-Michael addi-
tion pathway [Eq. (3)]. The isomeric mixture at the quater-
nary position of 2o is stereochemically inconsequential,
owing to the formation of the enol intermediate.
[a] Conditions A: AuCl3 (2 mol%) in CH2Cl2; Conditions B: AuCl3
(2 mol%) in CH3NO2; Conditions C: [{tBu2(o-Ph-C6H4)P}Au]NTf2
(5 mol%) in CH2Cl2 unless otherwise noted. [b] Yield of isolated
product(s) after chromatography (diastereomeric ratio from the
1H NMR spectrum of the crude mixture). [c] 2p and 2p’ were obtained
as an inseparable mixture. [d] 5 mol% catalyst. [e] A minor amount (21%
of 2v’, 27% of 2w’, or 25% of 2x’) of alkene migration was also obtained.
[f] The crude mixture was treated with silica gel (RT, 10 h) before
chromatography. Tf=trifluoromethanesulfonyl.
In summary, we have described a novel pinacol-Mannich-
Michael cascade, utilizing a metal carbenoid and an imine
generated from a gold-catalyzed redox reaction. The remark-
able versatility of these intermediates for cascade reactions
was demonstrated in highly diastereoselective, one-pot syn-
theses of various synthetically important skeletons, such as
spirocycles, 1-aminoindanes, and 5,6-fused azacycles at ambi-
ent temperature. Using the current protocol, we were able to
introduce various alkyl, alkenyl, alkynyl, and aryl groups at
the quaternary center. Furthermore, the mechanistic uncer-
tainty regarding the nature of the gold-catalyzed redox
chemistry of the nitrone became clear from the unambiguous
involvement of the carbenoid and the imine.[6b,19] Further
efforts in our laboratory are aimed at the target-oriented
synthesis of biologically active natural products utilizing this
atom-efficient, step-, and redox-economical approach.[1d]
substituted quaternary center, in 77% yield as a single
diastereomer. When 1v, derived from 2-cyclopentenone, was
treated with 5 mol% of [{tBu2(o-Ph-C6H4)P}Au]NTf2 in
dichloromethane, the 1H NMR spectrum of the crude mixture
indicated the preferential formation of alkyl shifted product
2v along with a small amount of alkene shifted by-product 2v’
in a ratio of approximately 3:1.[18] Upon treating this mixture
with silica gel in CH2Cl2, 2v was cleanly converted into its
Michael adduct (3v; isolated in 75% yield for the overall
cascade transformation). Alternatively, when the crude
reaction mixture was purified by chromatography on silica
gel (with 5% of triethylamine in the eluent), 2v was obtained
in 65% yield. Similarly, 2-cyclohexenone-derived 1w gave the
intramolecular Michael adduct 3w, whilst N-Ph nitrone 2x
was isolated without any Michael addition. The structures of
3v and 3w were confirmed by single-crystal X-ray analysis
(Figure S1).[13] We also examined various secondary alcohol
substrates with R1 = H and R2 = methyl, aryl, allyl, and vinyl
groups. However, unlike the reported propensity for hydro-
gen migration,[15] these reactions afforded only messy mix-
tures even after extensive trials.
Experimental Section
Representative procedure for the gold-catalyzed formation of 2v and
3v: [{tBu2(o-Ph-C6H4)P}Au]Cl (2.8 mg, 9.5 mmol, 5 mol%) and
AgNTf2 (3.6 mg, 9.5 mmol) were dissolved in dichloromethane
(3 mL) and substrate 1v (60.0 mg, 0.189 mmol) was added to the
mixture at room temperature. After 20 min, the reaction was judged
to be complete (TLC), and was quenched by addition of 3 drops of
Et3N. After removal of the solvent under vacuum, the residue was
purified using chromatography on silica gel (EtOAc/hexanes = 1:4
containing 5% Et3N) to afford 2v (65% yield). Alternatively, upon
completion of the reaction, the crude mixture was treated with silica
gel (approx. 50 mg) and was stirred overnight at room temperature.
The diverse heterocyclic structures obtained using our
cascade protocol could then be successfully transformed into
Angew. Chem. Int. Ed. 2010, 49, 1611 –1614
ꢀ 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.angewandte.org
1613

Communications
After evaporation of solvent and chromatography on silica gel
(EtOAc/hexanes = 1:4), 3v was obtained in 75% yield.
[8] a) X. Xiao, Z. H. Miao, S. Antony, Y. Pommier, M. Cushman,
Bioorg. Med. Chem. Lett. 2005, 15, 2795 – 2798; b) P. Selig, E.
Herdtweck, T. Bach, Chem. Eur. J. 2009, 15, 3509 – 3525.
[9] For discussions on the nature of the gold carbenoid, see: a) D.
Benitez, N. D. Shapiro, E. Tkatchouk, Y. Wang, W. A. God-
dard III, F. D. Toste, Nat. Chem. 2009, 1, 482 – 486; b) A.
Fꢃrstner, L. Morency, Angew. Chem. 2008, 120, 5108 – 5111;
Angew. Chem. Int. Ed. 2008, 47, 5030 – 5033.
[10] For b-keto carbonyl syntheses using a 1,2-alkyl shift, see: a) A.
Padwa, Y. S. Kulkarni, Z. Zhang, J. Org. Chem. 1990, 55, 4144 –
4153; b) C. R. Holmquist, E. J. Roskamp, J. Org. Chem. 1989, 54,
3258 – 3260; For pinacol shifts in gold-catalyzed reactions:
c) S. F. Kirsch, J. T. Binder, C. Liꢄbert, H. Menz, Angew.
Chem. 2006, 118, 6010 – 6013; Angew. Chem. Int. Ed. 2006, 45,
5878 – 5880; d) S. F. Kirsch, J. T. Binder, C. Liꢄbert, H. Menz,
Angew. Chem. 2007, 119, 2360 – 2363; Angew. Chem. Int. Ed.
2007, 46, 2310 – 2313; e) B. Crone, S. F. Kirsch, Chem. Eur. J.
2008, 14, 3514; f) B. Baskar, H. J. Bae, S. E. An, J. Y. Cheong,
Y. H. Rhee, A. Duschek, S. F. Kirsch, Org. Lett. 2008, 10, 2605 –
2607.
[11] To the best of our knowledge the Mannich-type reaction of an
enolate, formed from 1,2-shift of a metal carbenoid, has not been
reported. For Mannich additions via the trapping of a rhodium
carbenoid by the nucleophilic attack with an amine or alcohol,
see: a) H. Huang, X. Guo, W. Hu, Angew. Chem. 2007, 119,
1359 – 1361; Angew. Chem. Int. Ed. 2007, 46, 1337 – 1339;
b) C. D. Lu, H. Liu, Z. Chen, W. Hu, A. Mi, Org. Lett. 2005, 7,
83 – 86; c) Y. Zhu, C. Zhai, Y. Yue, L. Yang, W. Hu, Chem.
Commun. 2009, 1362 – 1364. For Mannich addition via 1,5-
hydride migration onto gold carbenoids, see Ref. [4e].
[12] See the Supporting Information for details of catalyst screening
(Table S1).
[13] CCDC 753771 (2e), 753772 (3v), and 753773 (3w) contain the
supplementary crystallographic data for this paper. These data
can be obtained free of charge from The Cambridge Crystallo-
graphic Data Centre via www.ccdc.cam.ac.uk/data_request/cif.
[14] For the cyclic substrates in Table 1, the diastereoselectivity
remained the same in CH2Cl2 or CH3NO2 solvent (Table S1).
[15] For previous studies of migratory aptitude onto a carbene center,
see: a) A. Nickon, Acc. Chem. Res. 1993, 26, 84 – 89; b) A. E.
Keating, M. A. Garcia-Garibay, K. N. Houk, J. Phys. Chem. A
1998, 102, 8467 – 8476; c) F. Xiao, J. Wang, J. Org. Chem. 2006,
71, 5789 – 5791; d) W. Shi, F. Xiao, J. Wang, J. Org. Chem. 2005,
70, 4318 – 4322; e) V. K. Aggarwal, C. G. Sheldon, G. J. Mac-
donald, W. P. Martin, J. Am. Chem. Soc. 2002, 124, 10300 – 10301;
f) See Ref. [4b].
Received: November 11, 2009
Published online: January 27, 2010
Keywords: carbenoids · cascade reactions · gold ·
.
Mannich reactions · redox chemistry
[1] For recent advances in hydrogen-transfer reactions, see: a) G.
Guillena, D. J. Ramꢀn, M. Yus, Angew. Chem. 2007, 119, 2410 –
2416; Angew. Chem. Int. Ed. 2007, 46, 2358 – 2364; b) J. F.
Bower, I. S. Kim, R. L. Patman, M. J. Krische, Angew. Chem.
2009, 121, 36 – 48; Angew. Chem. Int. Ed. 2009, 48, 34 – 46. For a
gold(I)-catalyzed hydrogen-transfer reaction, see: c) J. Bar-
ˇ
luenga, A. Fernꢁndez, F. Rodrꢂguez, F. J. Fananꢁs, Chem. Eur.
J. 2009, 15, 8121 – 8123. For a perspective on the redox economy,
see: d) N. Z. Burns, P. S. Baran, R. W. Hoffmann, Angew. Chem.
2009, 121, 2896 – 2910; Angew. Chem. Int. Ed. 2009, 48, 2854 –
2867.
[2] For selected examples of redox-economical processes, see:
a) B. M. Trost, N. Maulide, R. C. Livingston, J. Am. Chem. Soc.
2008, 130, 16502 – 16503; b) K. Y. K. Chow, J. W. Bode, 2004,
126, 8126 – 8127; c) F. Shibahara, J. F. Bower, M. J. Krische, J.
Am. Chem. Soc. 2008, 130, 6338 – 6339.
[3] For carbenes in organic synthesis, see: a) T. Ye, A. McKervey,
Chem. Rev. 1994, 94, 1091 – 1160; b) M. P. Doyle, A. G. H. Wee,
Modern Catalytic Methods for Organic Synthesis with Diazo
Compounds, Wiley, New York, 1998.
[4] a) N. D. Shapiro, F. D. Toste, J. Am. Chem. Soc. 2007, 129, 4160 –
4161; b) G. Li, L. Zhang, Angew. Chem. 2007, 119, 5248 – 5251;
Angew. Chem. Int. Ed. 2007, 46, 5156 – 5159; c) P. W. Davies,
S. J. C. Albrecht, Angew. Chem. 2009, 121, 8522 – 8525; Angew.
Chem. Int. Ed. 2009, 48, 8372 – 8375; d) L. Cui, G. Zhang, Y.
Peng, L. Zhang, Org. Lett. 2009, 11, 1225 – 1228; e) L. Cui, Y.
Peng, L. Zhang, J. Am. Chem. Soc. 2009, 131, 8394 – 8395;
f) A. B. Cuenca, S. Montserrat, K. M. Hossain, G. Mancha, A.
Lledꢀs, M. Medio-Simꢀn, G. Ujaque, G. Asensio, Org. Lett. 2009,
11, 4906 – 4909; g) G. Y. Lin, C. W. Li, S. H. Hung, R.-S. Liu, Org.
Lett. 2008, 10, 5059; h) A. S. K. Hashmi, M. Bꢃhrle, R. Salathꢄ,
J. W. Bats, Adv. Synth. Catal. 2008, 350, 2059 – 2064.
[5] For selected recent reviews on gold catalysis, see: a) A. S. K.
Hashmi, G. J. Hutchings, Angew. Chem. 2006, 118, 8064 – 8105;
Angew. Chem. Int. Ed. 2006, 45, 7896 – 7936; b) D. J. Gorin, F. D.
Toste, Nature 2007, 446, 395 – 403; c) A. Fꢃrstner, P. W. Davies,
Angew. Chem. 2007, 119, 3478 – 3519; Angew. Chem. Int. Ed.
2007, 46, 3410 – 3449; d) A. S. K. Hashmi, Chem. Rev. 2007, 107,
3180 – 3211; e) E. Jimꢄnez-Nfflnez, A. M. Echavarren, Chem.
Rev. 2008, 108, 3326 – 3350; f) A. S. K. Hashmi, M. Bꢃhrle, R.
Salathꢄ, J. W. Bats, Adv. Synth. Catal. 2008, 350, 2059 – 2064;
g) D. J. Gorin, B. D. Sherry, F. D. Toste, Chem. Rev. 2008, 108,
3351 – 3378.
[6] a) H. S. Yeom, J. E. Lee, S. Shin, Angew. Chem. 2008, 120, 7148 –
7151; Angew. Chem. Int. Ed. 2008, 47, 7040 – 7043; b) H. S.
Yeom, Y. Lee, J. E. Lee, S. Shin, Org. Biomol. Chem. 2009, 7,
4744 – 4752; For a related nitrone-mediated redox reaction, see:
c) K. Pati, R. S. Liu, Chem. Commun. 2009, 5233 – 5235.
[7] a) M. Froimowitz, K. M. Wu, A. Moussa, R. M. Haidar, J. Jurayj,
C. George, E. L. Gardner, J. Med. Chem. 2000, 43, 4981 – 4992;
b) X. Xiao, Z. H. Miao, S, Antony, Y. Pommier, M. Cushman,
Bioorg. Med. Chem. Lett. 2005, 15, 2795 – 2798; c) P. Selig, E.
Herdtweck, T. Bach, Chem. Eur. J. 2009, 15, 3509 – 3525; d) S.
Hayashibe, S. Yamasaki, N. Shiraishi, H. Hoshii, T. Tobe, PCT
Int. Appl., WO 2009069610, 2009; e) C. Liu, S. T. Wrobleski, K.
Leftheris, G. Wu, P. M. Sher, B. A. Ellsworth, U.S. Patent. Appl.
Publ., US2009041722, 2009.
[16] In the case of 1r–t, methyl shift products (2r’–2t’) could not be
observed.
[17] The reaction of 1t-Bn with N-Bn in the place of N-Ph gave a
lower ratio of vinyl versus alkyl migration (2:1, 55% total yield)
under Conditions A.
[18] The reaction of cyclic substrates with AuCl3 typically resulted in
a poorer ratio of alkyl and alkenyl shift products (approx. 1:1).
For details of catalyst optimization for the reaction of 1v, see the
Supporting Information (Table S2). Intriguingly, the selective
alkyl migration in cyclic substrates 1v–x is in sharp contrast to
vinyl migration in acyclic substrate 1t. The reason for this switch
of migratory aptitude is not clear and further mechanistic studies
are underway.
[19] Possible alternative mechanisms for the redox chemistry of the
nitrone: 1) [3+2] cycloaddition followed by a rearrangement
into acyl aziridines, 2) a 1,3-sigmatropic shift, or 3) via a diradical
intermediate. See: a) J. P. Freeman, Chem. Rev. 1983, 83, 241 –
261; b) J. A. Berson, Acc. Chem. Res. 1972, 5, 406 – 414; c) K.
Knobloch, K. W. Eberbach, Org. Lett. 2000, 2, 1117 – 1120.
1614
www.angewandte.org
ꢀ 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Angew. Chem. Int. Ed. 2010, 49, 1611 –1614