Camphor-derived sulfonylhydrazines: catalysts for Diels-Alder cycloadditions

Article abstract of DOI:10.1016/j.tetlet.2008.07.012

Camphor-derived sulfonylhydrazines proved to be very active for organocatalyzed Diels-Alder cycloadditions with cyclopentadiene. Good chemical yields and enantiomeric excesses up to 89% and 88% are obtained for endo/exo adducts.

Full text of DOI:10.1016/j.tetlet.2008.07.012

Tetrahedron Letters 49 (2008) 5576–5579
Contents lists available at ScienceDirect
Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
Camphor-derived sulfonylhydrazines: catalysts for Diels–Alder cycloadditions
*
Yves Langlois , Alain Petit, Pauline Rémy, Marie-Christine Scherrmann, Cyrille Kouklovsky
Laboratoire de Chimie des Procédés et des Substances Naturelles, UMR 8182, ICMMO, Université de Paris Sud, 91405 Orsay, France
a r t i c l e i n f o
a b s t r a c t
Article history:
Camphor-derived sulfonylhydrazines proved to be very active for organocatalyzed Diels–Alder cyclo-
additions with cyclopentadiene. Good chemical yields and enantiomeric excesses up to 89% and 88%
are obtained for endo/exo adducts.
Received 3 June 2008
Revised 25 June 2008
Accepted 1 July 2008
Available online 4 July 2008
Ó 2008 Published by Elsevier Ltd.
Since the pioneering work of McMillan and co-workers,1 the
enantioselective organocatalytic Diels–Alder cycloadditions have
been the topic of intense research developed in all fields of this
reaction.2–9 With the background of our previous experience of
the use of camphor-derived chiral auxiliaries,10 we selected cam-
phor sulfonylhydrazine derivatives, which could be prepared from
the relatively cheap camphorsulfonic acid available in both enan-
tiomeric forms, as potential catalysts in aldol and Diels–Alder reac-
tions. During the course of this study, Ogilvie demonstrated the
usefulness of camphoric acid hydrazide derivatives in the organo-
catalyzed Diels–Alder cycloadditions11 and published a remarkable
study concerning the mechanism of the reaction.11b,c As demon-
strated by this author, the rigidity of this new catalyst as well as
entry 1). After only 1 h, these adducts were still isolated in 81%
yield, thus demonstrating the efficiency of the catalyst under these
reaction conditions (entry 2).
In order to compare the enantiomerically enriched adducts with
the racemic coumpounds, cycloadditions were also achieved under
the same reaction conditions in nitromethane with N,O-dimethyl
hydroxylamine hydrochloride 9 as catalyst. Thus, racemic adducts
were isolated for comparison as carbonyl derivatives, which is not
the case if methanol is used as solvent.12a
Introduction of a side chain at the N-sulfonyl nitrogen proved
crucial to improve the enantioselectivity. Accordingly, hydrazone
4a was in turn N-alkylated to furnish the substituted hydrazones
4b–e. Despite numerous experiments, in our hands, the cyano-
borohydride reduction of substituted hydrazones 4b–e was never
complete and the corresponding hydrazines 5b–e were isolated
along with starting material which was recycled (Scheme 1).15
Cycloadditions with the benzyl-substituted hydrazine 5b were
achieved within 2 h in 73% yield and an increased enantioselectiv-
ity (ee endo: 87; ee exo: 85) (entry 3).
The absolute configuration of these endo and exo adducts was
deduced after comparison by chiral GC analysis with the corre-
sponding compounds obtained with the MacMillan catalyst.1a
Thus, for the endo adduct, for instance, the same type of transition
state model already proposed by Ogilvie and co-workers11c can be
proposed for these cycloadditions (Fig. 1).
the so-called
a
-effect12 explained its reactivity and selectivity.
The recent disclosure of camphorsulfonyl derivatives organocata-
lyzed Diels–Alder cycloadditions,13 prompts us to present our
own independent results in this field. According to Scheme 1,
camphorsulfonyl hydrazone 4a is prepared from (+)-camphorsul-
fonic acid 1 in almost quantitative yield in a sequence needing
no intermediate purification by a modification of the previous syn-
thesis.14 Cyanoborohydride reduction of hydrazone 4a afforded the
anticipated hydrazine 5a in 75% overall yield from 1.15
The efficiency of this new candidate for the Diels–Alder organ-
ocatalysis was further evaluated. The use of methanol as solvent
was precluded because, with a,b-unsaturated aldehydes, the corre-
sponding acetal adducts were isolated at the end of the reaction.1a
Screening of the best reaction conditions led us to select nitro-
methane as solvent and 0.5 N to 1 N perchloric acid to promote
the intermediate iminium formation. Under these conditions,
cycloaddition between cinnamaldehyde and cyclopentadiene in
the presence of 10% catalyst 5a afforded smoothly at room temper-
ature the corresponding adducts as a 40/60 mixture of endo–exo
isomers in 87% yield after 4 h.16 However, a moderate enantio-
selectivity was observed (ee endo: 30; ee exo: 62) (Table 1,
The amount of catalyst 5b can be diminished to 2% and afforded
after 16 h a mixture of adducts in 66% yield, however, with lower
enantioselectivity (entry 5). With lower amount of catalyst
(0.5%), both yield and enantioselectivity decreased dramatically
(entry 6). The absence of any chiral induction for the endo isomer
suggests that this compound could be the result of a cycloaddition
catalyzed with perchloric acid (Scheme 2).
The influence of modifications of the benzyl unit on the reactiv-
ity and on the selectivity of the catalyst was then studied. Results
are summarized in Table 1. With the 4-bromo benzyl derivative 5c
slightly better enantioselectivities were obtained (entry 7). How-
ever, introduction of electron-donating substituents in catalysts
* Corresponding author. Tel.: +33 1 69 15 76 30; fax: +33 1 69 15 46 79.
E-mail address: langlois@icmo.u-psud.fr (Y. Langlois).
0040-4039/$ - see front matter Ó 2008 Published by Elsevier Ltd.
doi:10.1016/j.tetlet.2008.07.012

Y. Langlois et al. / Tetrahedron Letters 49 (2008) 5576–5579
5577
O
S
eor f
O
SX
O
S
c
O
S
b
O
O
N
NR2
NR1
(from 2)
NHNH2
N
R
O
O
O
O
1 : X = OH
3
a
4a : R =H
5a : R1 = H; R2 = H
2: X = Cl
d
4b - 4e
5b : R1 = Bn; R2 = H
5c : R1 = p-BrC6H4CH2; R2 = H
5d : R1 = m-MeOC6H4CH2; R2 = H
5e : R1 = m,p-OCH2OC6H3CH2; R2 = H
5fh : R1 = H; R2 = p-BrC6H4CH2
g
b,c, f
(from 7)
MeNHOMe, HCl
O
SX
O
S
O
NH
9
O
N
H
O
6 : X = OH
a
8
7 : X = Cl
Scheme 1. Reagents and conditions: (a) SOCl2 (neat), 80 °C, 3 h; (b) NH2NH2 (4 equiv), Et3N, CH2Cl2, 20 h, rt; (c) PhMe, 80 °C, 3 h; (d) KHMDS, THF, ArCH2Br, ꢀ78 °C to 20 °C,
20 h; (e) NaBH3CN (3 equiv), THF/MeOH, MeOH/HCl 1 N, 0 °C; (f) NaBH3CN (10 equiv), AcOH/MeOH, rt; (g) PhCHO (1,1 equiv), tBuOK (4 equiv), PhMe, 80 °C 20 h; (h) see Ref.
17.
Table 1
Cycloadditions between cinnamaldehyde and cyclopentadiene
O
S
NH
NR
, HClO4(0.5N)
O
R1
R2
O
R2
(2 to 10% equiv.)
MeNO2, RT
+
+
R1
O
R2
R1
O
Entry
Cat. (%)
Time (h)
Yield (%)
endo/exoa
ee (%) endo/exoa
1
2
3
4
5
6
7
8
9
10
11
12
13
5a (10)
5a (10)
5b (10)
5b (5)
5b (2)
5b (0.5)
5c (10)
5d (10)
5e (6)
5f (10)
8 (5)
9 (20)
None
4
1
2
2
16
5
20
36
24
48
28
24
26c
87
81
73
51
66
20
52
32
60
11
73
32
6
40/60
40/60
40/60
50/50
56/44
70/30
50/50
60/40
65/35
93/7
30/62
n.d.b
87/85
72/82
46/70
0/40
89/88
20/82
26/88
0/0
44/56
36/64
58/42
30/20
—
—
a
Determined by GC with QC3/Cydex B, 25 m, OD 0.43 mm, film thickness 0.25 l.
Non-determined.
Temperature 70 °C.
b
c
5d and 5e which could stabilize the iminium intermediate main-
tains the same range of enantioselectivity for the exo isomer but
decreased significantly the ee value for the endo isomers (entries
8 and 9). This observation is not easily rationalized. In contrast
with the results observed by Lee and co-workers,13 when the basic
nitrogen is substituted in compound 5f,17 under our reaction con-
ditions, racemic adducts were isolated in low yield (entry 10). We
also examined the influence of introduction of an additional substi-
tuent in
a to the basic nitrogen. Thus, crotonization between (+)-
camphorsulfonic acid 1 and benzaldehyde gave benzylidene cam-
phorsulfonic acid 6.18 After the same sequence of reactions, this
compound afforded the anticipated benzylidene hydrazine deriva-
tive 8. However, this catalyst gave disappointing results and the
enantioselectivity was rather poor for both adducts (Table 1, entry
11).
R2
-
ClO4
+
O
N
S
NR1
Other Diels–Alder cycloadditions were subsequently examined
O
with these catalysts with different
a,b-unsaturated aldehydes
Figure 1.
and ketones. The results are summarized in Table 2. With the less

5578
Y. Langlois et al. / Tetrahedron Letters 49 (2008) 5576–5579
R
O
R
O
O
O
R
H
H
11a : R = Me
12a : R = Me
13
10a : R = H
10b : R = OMe
11b : R = Pr
12b : R = Et
Scheme 2.
Table 2
2458–2460. For the first example of organocatalyzed
Diels–Alder
cycloaddition, see: (c) Kelly, T. R.; Meghani, P.; Ekkundi, V. S. Tetrahedron
Lett. 1990, 31, 3381–3384.
Cycloadditions between dienophiles 10b–13 and cyclopentadiene
Entry Cat. (%) Dienophile Time (h) Yield (%) endo/exo ee (%) endo/exo
2. (a) Thayumanavan, R.; Dhevalapally, K.; Sakthivel, F.; Tanaka, F.; Barbas, C. F.,
III. Tetrahedron Lett. 2002, 43, 3817; (b) Braddock, D. C.; MacGilp, I. D.; Perry, B.
J. Adv. Synth. Catal. 2004, 346, 1117–1130; (c) Kim, K. H.; Lee, S.; Lee, D.-W.; Ko,
D.-H.; Ha, D.-C. Tetrahedron Lett. 2005, 46, 5991–5994; (d) Ishihara, K.; Nakano,
K. J. Am. Chem. Soc 2005, 127, 10504–10506; (e) Sakakura, A.; Suzuki, K.;
Nakano, K.; Ishihara, K. Org. Lett. 2006, 8, 2229–2232; (f) Bonini, B. F.; Capito,
E.; Comes-Franchini, M.; Fochi, M.; Ricci, A.; Zwanenburg, B. Tetrahedron:
Asymmetry 2006, 17, 3135–3143. Via microwave activation: (g) Mossé, S.;
Alexakis, A. Org. Lett. 2006, 8, 3577–3580; (h) Singh, R. P.; Bartelson, K.; Wang,
Y.; Heng, S.; Lu, X.; Deng, L. J. Am. Chem. Soc. 2008, 130, 2422–2433; Synthetic
applications: (i) Kinsman, A. C.; Ker, M. A. J. Am. Chem. Soc. 2003, 125, 14120–
14125; (j) Satoh, N.; Akiba, T.; Yokoshima, S.; Fukuyama, T. Angew. Chem., Int.
Ed. 2007, 46, 1–4. Organocatalyzed Diels–Alder cycloaddition theoretical
studies: (k) Gordillo, R.; Houk, K. N. J. Am. Chem. Soc. 2006, 128, 3543–3553.
3. Exo selective Diels–Alder cycloadditions: (a) Kano, T.; Tanaka, Y.; Maruoka, K.
Org. Lett. 2006, 13, 2687–2689; (b) Gotoh, H.; Hayashi, Y. Org. Lett. 2007, 9,
2859–2862; (c) Kano, T.; Tanaka, Y.; Maruoka, K. Chem. Asian J. 2007, 2, 1161–
1165.
1
2
3
4
5
6
7
8
9
10
11
12
13
14a
5b (10) 10b
9 (20) 10b
5b (10) 11a
9 (20) 11a
5b (10) 11b
24
36
24
28
20
24
20
3
24
20
20
5
68
10
88
72
95
67
57
75
56
90
96
28
62
73
42/58
54/46
68/32
47/53
74/26
70/30
60/40
97/3
95/5
94/6
95/5
93/7
—/78
—
40/—
—
26/42
0/0
—
0/0
0/0
—
0/0
8 (5)
9 (20)
11b
11b
5a (20) 12a
5b (5)
9 (20)
8 (5)
12b
12b
12b
5a (10) 13
5b (10) 13
5b (10) 10a
34/—
0/—
87/85
20
2
95/5
40/60
a
This experiment (Table 1, entry 3) has been added for comparison.
4. Inverse electron demand Diels–Alder cycloadditions: (a) Juhl, K.; Jorgensen, K.
A. Angew. Chem., Int. Ed. 2003, 42, 1498–1501; (b) Wabnitz, T. C.; Saaby, S.;
Jorgensen, K. Org. Biomol. Chem. 2004, 2, 828–834; (c) Wilson, R. M.; Jen, W. S.;
MacMillan, D. W. C. J. Am. Chem. Soc. 2005, 127, 11616–11617; (d) Hernandez-
Juan, F. A.; Cockfield, D. M.; Dixon, D. J. Tetrahedron Lett. 2007, 48, 1605–1608;
(e) Smith, C. D.; Batey, R. A. Tetrahedron 2007, 64, 652–663; (f) Xie, H.; Zu, L.;
Oueis, H. R.; Li, H.; Wang, J.; Wang, W. Org. Lett. 2008, 10, 1923–1926; (g) Zhao,
Y.; Wang, X.-J.; Liu, J. T. Synlett 2008, 1017–1020.
5. Hetero Diels–Alder cycloadditions: (a) Harriman, D. J.; Lambropoulos, A.;
Deslongchamps, G. Tetrahedron Lett. 2007, 48, 689–692; (b) Friberg, A.; Olsson,
C.; Ek, F.; Berg, U.; Fredj, T. Tetrahedron: Asymmetry 2007, 18, 885–891; (c)
Cafeo, G.; De Rosa, M.; Kohnke, F. H.; Neri, P.; Soriente, A.; Valenti, L.
Tetrahedron Lett. 2007, 49, 153–155; (d) Lu, L.-Q.; Xing, X.-. N.; Wang, X.-F.;
Ming, Z.-H.; Wang, H.-M.; Xiao, W.-J. Tetrahedron Lett. 2008, 49, 1631–1635; (e)
Aznar, F.; Garcia, A.-B.; Quinones, N.; Cabal, M.-P. Synthesis 2008, 479–484.
6. Intramolecular Diels–Alder cycloadditions: (a) Wilson, R. M.; Jen, W. S.;
MacMillan, D. W. C. J. Am. Chem. Soc. 2005, 127, 11616–11617; (b) Hong, B.-C.;
Tseng, H.-C.; Chen, S.-H. Tetrahedron 2007, 63, 2840–2850; (c) Gilmour, R.;
Prior, T.; Burton, J. W.; Holmes, A. B. Chem. Commun. 2007, 38, 3954–3956; (d)
Jacobs, W. C.; Christmann, M. Synlett 2008, 247–251.
reactive p-methoxy cinnamaldehyde 10b, catalyst 5b gave signifi-
cantly lower ee than with the unsusbstituted aldehyde 10a (entry
1). In the aliphatic series with catalyst 5b an increase of endo/exo
ratio was observed but the enantioselectity is dramatically reduced
for both adducts (entries 3 and 5). With the benzylidene catalyst 8,
racemic adducts were isolated (entries 6 and 11).
With a,b-unsaturated ketones as dienophiles, only the Mac Mil-
lan catalyst1b has given good stereoselectivity in organocatalyzed
Diels–Alder cycloadditions. It turned out that in our case, no
enantioselectivity was observed. In contrast to the observation of
Mac Millan,1b in our conditions, the use of hexenone 12b instead
of pentenone 12a19 did not improve the enantioselectivity (entries
8, 9, and 11). Nevertheless, high endo selectivity and often good
yields were obtained (entries 8 and 9–11). The case of cyclopente-
none 13 is not worthy, with catalyst 5a, the endo adduct was ob-
tained with 30% ee (entry 12) but with 5b, the same adduct was
found to be racemic.
7. Domino and cascade organocatalyzed
Diels–Alder cycloadditions: (a)
Ramachary, D. B.; Chowdari, N. S.; Barbas, C. F., III. Angew. Chem., Int. Ed.
2003, 42, 4233–4237; (b) Ramachary, D. B.; Anebouselvy, K.; Chowdari, N. S.;
Barbas, C. F., III. J. Org. Chem. 2004, 69, 5838–5849; (c) Enders, D.; Huttl, M.;
Runsink, J.; Raabe, G.; Wendt, B. Angew. Chem., Int. Ed. 2007, 46, 467–469; (d)
Pizzirani, D.; Roberti, M.; Recanatini, M. Tetrahedron Lett. 2007, 48, 7120–7124.
8. Solid supported catalyst: (a) Selkälä, S. A.; Tois, J.; Pihko, P. M.; Koskinen, A. M.
P. Adv. Synth. Catal. 2002, 344, 941–945. Recyclable fluorous catalyst: (b) Chu,
Q.; Zhang, W.; Curran, D. P. Tetrahedron Lett. 2006, 47, 9287–9290.
9. Organocatalyzed Diels–Alder cycloaddition reviews: (a) Diez, H.; Ley, S.
Chemtracts 2000, 13, 592–596; (b) Notz, W.; Tanaka, F.; Barbas, C. F., III. Acc.
Chem. Res. 2004, 37, 580–591. Multicomponent: (c) Guillena, G.; Ramon, D.;
Yus, M. Tetrahedron: Asymmetry 2007, 18, 693–700; N-heterocyclic carbenes:
(d) Enders, D.; Niemeier, O.; Henseler, A. Chem. Rev. 2007, 107, 5606–
5655.
10. (a) Kouklovsky, C.; Pouilhès, A.; Langlois, Y. J. Am. Chem. Soc. 1990, 112, 6672–
6679; (b) Dirat, O.; Kouklovsky, C.; Mauduit, M.; Langlois, Y. Pure Appl. Chem.
2000, 72, 1721–1737; For a review concerning the use of camphor derivatives
in asymmetric synthesis see: (c) Oppolzer, W. Pure Appl. Chem. 1990, 62, 1241–
1250.
11. (a) Lemay, M.; Ogilvie, W. W. Org. Lett. 2005, 7, 4141; (b) Lemay, M.; Ogilvie, W.
W. J. Org. Chem. 2006, 71, 4663; (c) Lemay, M.; Aumand, L.; Ogilvie, W. W. Adv.
Synth. Catal. 2007, 349, 441.
In summary, under our reaction conditions, camphor-derived
sulfonyl hydrazines, easily prepared from camphorsulfonic acid,
showed to be very active organocatalysts in Diels–Alder cycloaddi-
tions. Racemic adducts were easily prepared for comparison with
N,O-dimethyl hydroxylamine as catalyst. As often with other
organocatalysts, the endo/exo selectivity as well as the enantio-
selectivity are difficult to be rationalized. Endo and exo adducts
are probably obtained with different relative kinetic constants.
Further studies towards the synthesis of supported camphor-
derived organocatalysts are in current development.
Acknowledgments
We are grateful to Dr. R. Lett for very stimulating discussions
and Pr. Ogilvie for providing us experimental details concerning
his work.
12. (a) Cavill, J. L.; Peters, J.-W.; Tomkinson, N. C. O. Chem. Commun. 2003, 728–
729; (b) Cavill, J. L.; Eliott, R. L.; Evans, G.; Jones, I. L.; Platts, J. A.; Ruda, A. M.;
Tomkinson, N. C. O. Tetrahedron 2006, 62, 410–421.
13. He, H.; Pei, B.-J.; Chou, H.-H.; Tian, T.; Chan, W.-H.; Lee, A. W. M. Org. Lett. 2008,
10, 2421–2424.
References and notes
14. Cremlyn, R.; Burrell, K.; Fish, K.; Hough, I.; Mason, D. Phosphorous Sulfur 1982,
12, 197–204.
1. (a) Ahrendt, K. A.; Borths, C. J.; MacMillan, D. W. C. J. Am. Chem. Soc. 2000, 122,
4243–4244; (b) Northrup, A. B.; MacMillan, D. W. C. J. Am. Chem. Soc. 2002, 124,
15. Preparation of compound 4a: SOCl2 (3.64 mL, 25 mmol) was added dropwise to
crystalline (+)-camphorsulfonic acid 1 (4,64 g, 20 mmol) under argon. The

Y. Langlois et al. / Tetrahedron Letters 49 (2008) 5576–5579
5579
brown reaction medium was then heated at 80 °C for 3 h. The resulting brown
slurry was poured into ice and then extracted with CH2Cl2 affording crude 2. To
a solution of NH2NH2 (64% in H2O, 80 mmol, 4 mL) and Et3N (80 mmol, 6 mL)
in CH2Cl2 (50 mL) was added dropwise a solution of crude 2 (20 mmol) in
CH2Cl2 (50 mL). The reaction medium was stirred for 20 h at room
temperature, extracted with CH2Cl2, washed three times with H2O and then
with brine. After evaporation, the crude compound 3 was dissolved in toluene
(20 mL) and heated at 80 °C for 3 h. Evaporation of solvent afforded compound
solution of KHMDS (0.5 M in toluene, 2.2 mmol, 4.4 mL). The temperature of
the reaction medium was leaf to raise to 0 °C in 30 min and recooled to ꢀ78 °C.
BnBr (240 lL, 2 mmol.) was then added dropwise and the reaction was stirred
at room temperature for 16 h. Reaction medium was extracted with CH2Cl2,
washed successively with aqueous NaHCO3 (5%) and brine. The crude product
was purified by SiO2 chromatography (heptane/tBuOMe 60/40) affording 4b
(570 mg, 89%). ½a D22
ꢁ
ꢀ80 (c 0.95, CHCl3); 1H NMR 360 MHz, CDCl3, d, ppm: 7.6–
7.2 (m, 5H), 4.9 (d, J = 14, 1H), 4.6 (d, J = 14, 1H), 3.2 (d, J = 14, 1H), 3.1 (d, J = 14,
1H), 2.6–2.5 (2t, 1H), 2.5–2.3 (m, 1H), 2.1–1.3 (m, 4H), 0.9 (s, 3H), 0.8 (s, 3H).
13C NMR, 75 MHz, CDCl3, d, ppm: 165.3, 136.5, 129.9, 128.6, 127.5, 56.0, 53.0,
49.0, 48.5, 44.0, 36.2, 31.0, 27.0, 19.8, 18.0. MS(ESI+) m/z: 341 (M+23), 318.
4a (4,1 g, 90%). Compound 4a: ½a D22
ꢁ
ꢀ12 (c 1.47, CHCl3); 1H NMR 360 MHz,
CDCl3, d, ppm, J Hz: 7.1 (s, 1H), 3.28 (d, J = 14, 1H), 3.16 (d, J = 14, 1H), 2.5 (m,
1H), 2.4 (m, 1H), 2.2–1.4 (m, 5H), 1.1 (s, 3H), 0.9 (s, 3H). 13C NMR, 90 MHz,
CDCl3, d, ppm: 165.1, 56.1, 49.3, 48.5, 45.6, 36.0, 31.4, 27.3, 20.0, 18.0. MS(ESI+)
m/z: 251 (M+23), 228. Preparation of compound 5a: To a cooled solution (0 °C)
of 4a (320 mg, 1.4 mmol) and small amount of methyl orange in THF/MeOH
(50/50, 12 mL) was added NaBH3CN (210 mg, 3.3 mmol) portionwise in 1 h.
The pH was maintained around 3.8 by the addition of a solution HCl/MeOH
(1 N). After an additional hour, the reaction medium was extracted with CH2Cl2
and the organic layer was washed successively with H2O/NH4Cl, H2O/NaHCO3
and brine. After chromatography (SiO2, heptane/AcOEt 50/50) compound 5a
Compound 5b: ½a 2D2
ꢁ
ꢀ80 (c 1.05, CHCl3); 1H NMR 360 MHz, CDCl3, d, ppm: 7.5–
7.2 (m, 5H), 4.6 (d, J = 14, 1H), 4.1 (d, J = 14, 1H), 3.4 (d, J = 14, 1H), 3.2 (d, J = 14,
1H), 3.2 (m, 1H), 1.8–1.4 (m), 1.35 (s, 3H), 1.4–1 (m, 2H), 0.95 (s, 3H). 13C NMR,
90MHz, CDCl3, d, ppm: 136, 128.6, 128.3, 127.6, 62.5, 51.3, 50.7, 50.4, 46.7,
45.2, 37.1, 34.2, 25.9, 21.1, 20.6. MS(ESI+) m/z: 321 (M+1).
16. Typical experiment for cycloaddition: To a solution of catalyst 5b (16 mg,
0.05 mmol) in nitromethane (900
lL) was added successively, HClO4 (0.5 N,
1 equiv, 100 L), aldehyde (0.5 mmol) and cyclopentadiene (1.5 mmol) under
l
was isolated in 83% yield. Compound 5a: ½a D22
ꢁ
ꢀ82 (c 1.3, CHCl3); 1H NMR
argon. The reaction medium was vigourously stirred at room temperature and
the reaction was monitored by TLC (SiO2, heptane/tBuOMe: 80/20 to 60/40). At
the end of the reaction, the reaction medium was poured in CH2Cl2, washed
with aqueous NaHCO3 (5%) and brine. After drying over MgSO4, filtration and
evaporation, the crude mixture was purified by preparative TLC.
17. Compound 5f was prepared by alkylation of compound 5a with pBr-C6H4CH2Br
after deprotonation with KHMDS.
18. (a) Bouillon, C.; Vayssie, C.; Richard, F. U.S. Patent 1,165,336, 1982.
19. Racemic adduct (entry 8) was prepared according to: Stork, G.; Guthikonda, R.
N. Tetrahedron Lett. 1972, 27, 2755–2758.
360 MHz, CDCl3, d, ppm: 5.5 (s, 1H), 4.2 (br s, 1H), 3.36 (d, J = 12, 1H), 3.12 (d,
J = 12, 1H), 3.08 (m, 1H), 1.9–1.5 (m, 5H), 1.36 (s, 3H), 1.34–1.08 (m, 2H), 0.96
(s, 3H). 13C NMR, 90 MHz, CDCl3, d, ppm: 63.0, 50.0, 49.5, 47.0, 45.8, 37.8, 34.0,
26.2, 21.2, 20.5. MS(ESI+) m/z: 253 (M+23), 230. Compounds 5b and 5d were
prepared by reduction of 4b and 4d with the same protocol (5b 40%, recovery
of starting material 47%; 5d, 33%). Compounds 5c and 5e were prepared by
NaBH3CN (10 equiv) reduction in AcOH/MeOH (2/1) according to Ref. 11a (5c
40%, 5e 33%, SM 42%). Preparation of compound 4b: To a solution of 4a
(456 mg, 2 mmol) in THF (10 mL) under argon at ꢀ78 °C was added dropwise a