Synthesis and stereochemistry of (-)-rosiridol and (-)-rosiridin

Article abstract of DOI:10.1016/j.tetlet.2008.07.018

The plant-derived monoterpenoids (-)-rosiridol and (-)-rosiridin can be assembled in an enantioselective manner via DIP-Cl reduction of a ketone precursor obtained by BCl₃-mediated C-C coupling of prenyl stannane and an α,β-unsaturated C₅ aldehyde. On the basis of Mosher analyses, the absolute stereochemistry 4S was assigned to (-)-rosiridol; this was confirmed by X-ray structure analysis of pentaacetylrosiridin. Glucosylation of (4S)-4-acetoxygeraniol proceeds under Koenigs-Knorr conditions in diethyl ether. (-)-Rosiridin was synthesized for the first time.

Full text of DOI:10.1016/j.tetlet.2008.07.018

Tetrahedron Letters 49 (2008) 5580–5582
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Tetrahedron Letters
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Synthesis and stereochemistry of (ꢀ)-rosiridol and (ꢀ)-rosiridin
*
Elisabeth Schöttner, Kristina Simon, Manuel Friedel, Peter G. Jones, Thomas Lindel
Technische Universität Braunschweig, Institutes of Organic, Inorganic and Analytical Chemistry, 38106 Brunswick, Germany
a r t i c l e i n f o
a b s t r a c t
Article history:
The plant-derived monoterpenoids (ꢀ)-rosiridol and (ꢀ)-rosiridin can be assembled in an enantioselec-
Received 16 April 2008
Revised 27 June 2008
Accepted 1 July 2008
Available online 4 July 2008
tive manner via DIP–Cl reduction of a ketone precursor obtained by BCl3-mediated C–C coupling of prenyl
stannane and an a,b-unsaturated C5 aldehyde. On the basis of Mosher analyses, the absolute stereochem-
istry 4S was assigned to (ꢀ)-rosiridol; this was confirmed by X-ray structure analysis of pentaacetylrosir-
idin. Glucosylation of (4S)-4-acetoxygeraniol proceeds under Koenigs–Knorr conditions in diethyl ether.
(ꢀ)-Rosiridin was synthesized for the first time.
Keywords:
Monoterpenoids
DIP–Cl
Ó 2008 Elsevier Ltd. All rights reserved.
Mosher method
Prenyl nucleophiles
Natural products
Exploring the synthesis of cladiellane diterpenoids,1 we became
interested in the hydroxylated monoterpenoid (ꢀ)-rosiridol [(ꢀ)-1,
(ꢀ)-4-hydroxygeraniol]. (ꢀ)-Rosiridol [(ꢀ)-1] has been isolated as
a natural product from the rhizome of the medicinal plant Rhodiola
rosea2–4 (Crassulaceae, roseroot), from the leaves of Cunila spicata
(Lamiaceae),5 and was detected in petals of the rose Rosa
damascena.6
independent synthesis of (ꢀ)-rosiridol and a first synthesis of
(ꢀ)-rosiridin [(ꢀ)-2] might shed some light on that issue.
Hong et al. published the only total synthesis of (ꢀ)-1 by
coupling prenylzinc to a C5 aldehyde in the presence of HMPA
and a norbornene-derived chiral auxiliary under precisely defined
conditions strongly dependent on the reaction time.13
Synthesis of rac-rosiridol. We first synthesized rac-rosiridol
(rac-1) to obtain NMR data of both Mosher esters. Aldehyde 5
was prepared from prenol (3) in three steps (Scheme 1).14 The con-
comitantly formed allylic alcohol 4 was oxidized to 5 with IBX.
Regarding the regioselective SN2 addition of the prenyl nucleophile
to a carbonyl group,15 a procedure first employed by Danishefsky
and co-workers worked best.16 BCl3 was rapidly added to a cooled
solution of aldehyde 5 and stannane 6 leading to the desired
alcohol rac-7 via transmetalation of the prenyl moiety from tin
to boron (Scheme 1). We observed formation of the regioisomeric
SN20 product when the stannane 6 was prepared from prenyl bro-
mide, whereas use of prenyl chloride led to complete SN2
regioselectivity.17
Removal of tin containing impurities was possible by column
filtration on KF–silica (1:9) leaving the OTPS group intact.18 Depro-
tection under standard conditions afforded rac-rosiridol (rac-1) in
80% yield.19
Diastereomeric (R)-Mosher esters 8 and 9 were synthesized
from rac-7 (Scheme 1, Fig. 1) employing (S)-MTPA–Cl20 and were
analyzed by 1H NMR spectroscopy (8: (R,4R), 9: (R,4S)).21 The
(R,R)-diastereomer 8 must exhibit the same 1H NMR chemical
shifts as the (S,S)-compound, which are to be compared with that
of (S,R)-diastereomer 9. We also desilylated 8 and 9 affording the
4-O-MTPA esters of rac-1, which exhibited 1H NMR chemical shifts
HO
OH
4
4
OH
OH
O
OH
O
6'
OH
OH
(−)-rosiridol ((−)-1)
(−)-rosiridin ((−)-2)
Glycosylated derivatives of (ꢀ)-rosiridol [(ꢀ)-1] include the ma-
jor component (ꢀ)-rosiridin [(ꢀ)-2] from Rh. rosea2,7 and rhodiolo-
sides B and C from Rhodiola sachalinensis.8,9 A rosiridyl side chain
occurs in the tyramine derivative acidissiminol from the wood ap-
ple tree Limonia acidissima10 and in a 5-methylcoumarin from
Mutisia orbignyana (Asteraceae).11 The carbon skeleton of the mar-
ine triterpenoid glycoside xestovanin A contains a 4-hydroxygera-
nyl partial structure.12
There are contradicting reports on the absolute stereochemistry
of (ꢀ)-rosiridol. While Kadota et al.7 and Koike et al.8 concluded
that (ꢀ)-rosiridol [(ꢀ)-1] should have 4R configuration, Hong
et al.13 and Yoshikawa et al.9 derived 4S configuration. An
* Corresponding author. Tel.: +49 531 391 7300; fax: +49 531 391 7744.
E-mail address: th.lindel@tu-bs.de (T. Lindel).
0040-4039/$ - see front matter Ó 2008 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2008.07.018

E. Schöttner et al. / Tetrahedron Letters 49 (2008) 5580–5582
5581
IBX,
(−)-DIP-Cl (11),
Et2O, 0 ºC to rt,
40 h, 44%
HO
O
DMSO,
OTPS
15 h, rt
rac-7
1) TPS-Cl, imidazole,
DMF, rt, 22 h, 99%
OTPS
IBX,
4
+
DMSO,
rt, 15 h
90%
O
88%
BCl
OH
10
2) SeO2, salicylic acid,
tBuOOH, DCM,
0 °C to rt, 46 h, 73%
11
3
2
OTPS
Ac2O, NEt3,
DMAP,DCM,
17 h, rt
5
OTPS
OTPS
85%
OAc
OH
(4
6
Sn(n-Bu)3
OTPS
S
)-7
(4S)-12
BCl3, DCM,
-78 °C, 8 min, 62%
OH
rac-
1) TBAF, THF,
75%
7
2) Ag2CO3, Et2O,
20 h, rt, 26%
TBAF, THF,
RT, 2 h, 55%
Br
OAc
TBAF,
OAc
OAc
OAc
(S)-MTPA-Cl,
75%
THF,
80%
pyr, rt, 40 h,
(
((
S
)-(−)-rosiridol
O
S)-1), 94% ee
13
1.34
5.33
2.22 1.47
2.39
2.27
2.46
1.60
1.70
1.54
1.63
AcO
4.24
OTPS
4.21
OTPS
OAc
OAc
5.37
4
4S
5.71
(S
)-MTPA-Cl,
Pyr, rt, 20 h
O
4.93
4R
5.06
5.77
O
OAc
+
OAc
O
O
O
O
(4S)-14
72%
R
R
Ph
F3C
Ph
F3C
NaOMe, MeOH
3h, rt, 96%
O
O
1
rac-
8
9
9
(−)-rosiridin ((−)-2)
Scheme 1. Synthesis and Mosher analysis of rac-rosiridol (rac-1). 1H NMR chemical
Scheme 2. Synthesis of (ꢀ)-rosiridol [(ꢀ)-1] and (ꢀ)-rosiridin [(ꢀ)-2].
shifts were obtained in CDCl3.
tion.8 The 1H NMR chemical shift differences reported for the
Mosher esters of rosiridyl 1-O-pivaloate almost exactly mirror
our data, but with opposite sign. The 1H NMR chemical shift differ-
ences observed for the 4,60-bis-Mosher esters of (ꢀ)-rosiridin [(ꢀ)-
2] obtained by Kadota et al. are quite small and difficult to compare
with our values.7 The Kadota and Koike groups both conclude that
(ꢀ)-rosiridol [(ꢀ)-1] has R configuration. Contrastingly, Hong et al.
base their opposite 4S assignment for (ꢀ)-rosiridol [(ꢀ)-1] not only
on the Mosher esters of the TBS-protected analog of [(ꢀ)-1], but
also on the conversion of the compound to the pheromone (ꢀ)-
eldanolide.13 The absolute stereochemistry of (ꢀ)-eldanolide had
been proven earlier by total synthesis.23 Our own Mosher analysis,
in accordance with the expected stereoselectivity of the (ꢀ)-DIP–Cl
reduction, lets us draw the same conclusion as the Hong and Yos-
hikawa groups proposing 4S configuration for (ꢀ)-rosiridol [(ꢀ)-1].
Glucosylation. (4S)-4-O-Acetylrosiridol24 was obtained from
(4S)-7 in the presence of DMAP, followed by desilylation of (4S)-
12 (Scheme 2).25 Koenigs–Knorr glucosylation employing tetra-
Figure 1. Structure of pentaacetylrosiridol [(4S)-14] in the crystal, obtained by
recrystallization from EtOH.29
corresponding well to those of 8 and 9. The bulky TPS group does
not appear to substantially change the average conformation of
the Mosher esters.
Enantioselective synthesis of (ꢀ)-rosiridol. Alcohol rac-7 was oxi-
dized with IBX affording ketone 10 (Scheme 2). For the reduction of
10 we employed (ꢀ)-DIP–Cl (11)20 and obtained alcohol (4S)-7. Re-
moval of the TPS group afforded (ꢀ)-rosiridol [(ꢀ)-1] with negative
acetylated
a-glucopyranosyl bromide (13) in the presence of
Ag2CO3 in Et2O26 provided the peracetylated compound (4S)-14
in 26% isolated yield after chromatography with 15% recovered
starting material.27 Glucosylations carried out in DMF as described,
for example, for xylosylations by Satgé et al.28 were unsatisfactory
in our hands. In a prior model reaction, glucosylation of geraniol
provided the b-glucoside in an isolated yield of 34% after chroma-
tography with 20% recovered starting material. These non-opti-
mized yields are within the range of expectation for
glucosylations of geraniol derivatives. We were able to determine
the stereochemical outcome of the (ꢀ)-DIP–Cl reduction indepen-
dently by X-ray analysis of crystalline pentaacetylrosiridin [(4S)-
14, Fig. 1]; the absolute configuration was determined on the basis
optical rotation (½a D20
ꢀ7.2, c 0.36, acetone), proving its identity
ꢁ
with the natural product. The enantioselectivity of ketone reduc-
tions with (ꢀ)-DIP–Cl predicts the formation of the (S)-enantio-
mer.22 The absolute stereochemistry of (4S)-7 was confirmed by
1H NMR spectroscopy of the (R)-Mosher ester 9 and comparison
with the data obtained on derivatization of rac-7. The enantiomeric
ratio of (4S)-7 and (4R)-7 obtained by the (ꢀ)-DIP-Cl reduction was
about 97:3 (1H NMR analysis). We additionally confirmed this by
using (R)-MTPA–Cl.20
Koike et al. obtained rosiridyl 1-O-pivaloate by enzymatic
hydrolysis of the diglycoside rhodioloside B, followed by esterifica-

5582
E. Schöttner et al. / Tetrahedron Letters 49 (2008) 5580–5582
of anomalous scattering by oxygen.29 Saponification with NaOMe/
MeOH liberated (ꢀ)-(4S)-rosiridin (96%).
2876 (m), 2860 (m), 1671 (w), 1441 (m), 1378 (m), 1315 (w), 1096 (w), 1045
(m), 994 (s), 881 (w), 833 (w), 569 (m). UV–vis (MeOH): kmax (lge) = 202 nm
(3.97). HRMS (GC–MS): calcd C10H16O [MꢀH2O]+: 152.1201; found: 152.1215.
The maximum deviation of 13C NMR chemical shifts (methanol-
d4) of (ꢀ)-(4S)-rosiridin, when compared with the data reported by
Kadota7 and, recently, by Yoshikawa,9 was 0.9 and 0.2, respec-
tively. In a control experiment we synthesized diastereomeric
(ꢀ)-(4R)-rosiridin. Alcohol (4R)-7 was obtained by reduction of
10 with (+)-DIP–Cl, followed by acetylation, glucosylation (30 °C,
44%), and saponification. 4S- and 4R-rosiridins exhibit very similar
13C NMR chemical shifts, with the largest difference of 0.2 ppm ob-
served for C-30 (methanol-d4). Optical activities were also compa-
½
a 2D5
ꢁ
ꢀ7.2 (c 0.36, acetone). CD (TFE): kmax
(De) = 192 (ꢀ8.49), 206 (1.41),
212 nm (ꢀ0.38 molꢀ1 dm3 cmꢀ1).
20. (ꢀ)- and (+)-MTPA–Cl were purchased from Acros. (ꢀ)-DIP–Cl and (+)-DIP-Cl
were purchased from Sigma Aldrich.
21. Ohtani, I.; Kusumi, T.; Kashman, Y.; Kakisawa, H. J. Am. Chem. Soc. 1991, 113,
4092–4096.
22. Brown, H. C.; Chandrasekharan, J.; Ramachandran, P. V. J. Am. Chem. Soc. 1988,
110, 1539–1546.
23. Vigneron, J. P.; Méric, R.; Larchevêque, M.; Debal, A.; Kunesch, G.; Zagatti, P.;
Gallois, M. Tetrahedron Lett. 1982, 23, 5051–5054.
24. Iriye, R.; Uno, T.; Ohwa, I.; Konishi, A. Agric. Biol. Chem. 1990, 54, 1841–1843.
25. Characterization of (ꢀ)-(4S)-12: Rf (PE/EtOAc, 40:1) = 0.14. 1H NMR (400 MHz,
CDCl3): d = 7.70–7.66 (m, 4H, o-Ph-H), 7.44–7.35 (m, 6H, m-Ph-H, p-Ph-H),
5.66–5.62 (m, 1H, OCH2CH), 5.09 (t, 3J = 6.9 Hz, 1H, CHO), 5.04–4.99 (m, 1H,
(CH3)2CCH), 4.24 (d, 3J = 5.9 Hz, 2H, OCH2CH), 2.37–2.20 (m, 2H, CH2CHOH),
2.03 (s, 3H, CH3CO), 1.68 (d, 4J = 1.1 Hz, 3H, (CH3)2C), 1.61 (d, 4J = 0.6 Hz, 3H,
(CH3)2C), 1.43 (d, 4J = 1.1 Hz, 3H, CCH3), 1.04 (s, 9H, (CH3)3C). 13C NMR
(100 MHz, CDCl3): d = 170.2 (1C, CH3COO), 135.6 (4C, o-Ph-C), 134.2 (1C,
CHCCH3), 134.2 (1C, (CH3)2C), 133.8 (2C, PhCq), 129.6 (2C, p-Ph-C), 127.6 (4C,
m-Ph-C), 127.3 (1C, OCH2CH), 119.0 (1C, (CH3)2CCH), 78.1 (1C, CHO), 60.7 (1C,
OCH2CH), 31.6 (1C, CH2CHOH), 26.8 (3C, (CH3)3C), 25.8 (1C, (CH3)2C), 21.2 (1C,
CH3COO), 19.1 (1C, (CH3)3C), 17.9 (1C, (CH3)2C), 12.6 (1C, CH3C). IR (ATR):
rable (½a 2D6
ꢁ
ꢀ33.4 (4S), c 0.9 (good agreement with Kurkin2 and
Yoshikawa9) and ꢀ22.5 (4R), c 1.6, acetone, respectively). For the
diastereomeric pentaacetylrosiridins (4S)-14 and (4R)-14, how-
ever, the difference in optical rotation was more significant (½a D28
ꢁ
ꢀ24.5 (4S), c 1.0 and ꢀ4.9 (4R), c 1.0, acetone, respectively). Kurkin
et al. had reported ½a D20
ꢁ
ꢀ28.4 (c 1.0, acetone) for (4S)-14.2 This
leads us to conclude that the natural product (ꢀ)-rosiridin has 4S
configuration.
ꢀ1
~
m
¼ 3072 cm (w), 3050 (w), 2959 (w), 2932 (w), 2893 (w), 2858 (w), 1737
(m), 1471 (w), 1428 (w), 1369 (w), 1237 (s), 1110 (m), 1067(m), 1046 (m),
1019 (m), 938(w), 823 (m), 786 (w), 740 (m), 703 (s), 611 (m). UV–vis (MeOH):
Acknowledgment
kmax (lg
e) = 203 (4.54), 217 nm (4.27). MS (ESI): m/z (%): 473 (100), 474 (35),
475 (8). HRMS (ESI): calcd C28H38O3SiNa [M+Na]+: 473.2488, found: 473.2495.
Financial support was provided in part by the Fonds der Chem-
ischen Industrie (doctoral stipend to M.F.).
½ ꢁ ꢀ9.6 (c 0.48, acetone).
a 2D5
26. (a) Biesalski, H.-K.; Doepner, G.; Kunz, H.; Paust, J.; John, M. Liebigs Ann. Chem.
1995, 717–720; (b) Patov, S. A.; Punegov, V. V.; Kuchin, A. V.; Frolova, L. L.
Chem. Nat. Compd. 2006, 42, 431–433.
References and notes
27. Characterization of (ꢀ)-(4S)-14: Rf (PE/EtOAc, 2:1) = 0.25. 1H NMR (400 MHz,
CDCl3): d = 5.53–5.50 (m, 1H, OCH2CH), 5.20 (t, 3J = 9.5 Hz, 1H, 2-H), 5.12–5.06
(m, 2H, COOCH, 4-H), 5.04–4.97 (m, 2H, (CH3)2CCH, 3-H), 4.51 (d, 3J = 8.0 Hz,
1H, 1-H), 4.26–4.15 (m, 4H, OCH2CH, 6-H2), 3.69–3.64 (m, 1H, 5-H), 2.42–2.24
(m, 2H, CH2CHO), 2.09 (s, 3H, 6-OAc), 2.05 (m, 6H, CH3COO–CH, 4-OAc), 2.03 (s,
3H, 2-OAc), 2.00 (s, 3H, 3-OAc), 1.70 (m, 3H, (CH3)2C), 1.65 (s, 3H, CCH3), 1.62
(s, 3H, (CH3)2C). 13C NMR (100 MHz, CDCl3): d = 170.6 (1C, CH3COO–C6), 170.3
(1C, CH3COO–C3), 170.2 (1C, CH3COO–CH), 169.4 (1C, CH3COO–C2), 169.3 (1C,
CH3COO–C4), 138.5 (1C, CHCCH3), 134.6 (1C, (CH3)2C), 122.4 (1C, OCH2CH),
118.7 (1C, (CH3)2CCH), 99.1 (1C, C1), 77.9 (1C, C4), 72.9 (1C, C2), 71.8 (1C, C5),
71.3 (1C, C3), 68.5 (1C, CHO), 64.9 (1C, OCH2CH), 62.0 (1C, C6), 31.6 (1C,
CH2CHO), 25.8 (1C, (CH3)2C), 21.2 (1C, CH3COO–CH), 20.7 (1C, CH3COO–C6),
20.7 (1C, CH3COO–C4), 20.6 (1C, CH3COO–C3), 20.6 (1C, CH3COO–C2), 17.9 (1C,
1. Friedel, M.; Golz, G.; Mayer, P.; Lindel, T. Tetrahedron Lett. 2005, 46, 1623–1626.
2. Kurkin, V. A.; Zapesochnaya, G. G.; Shachvlinskii, A. N. Khim. Prir. Soedin. 1985,
5, 632–636; . Chem. Nat. Comp. 1986, 21, 593–597.
3. Bykov, V. A.; Zapesochnaya, G. G.; Kurkin, V. A. Khim. Farm. Zhurn. 1999, 33, 28–
39; . Pharm. Chem. J. 1999, 33, 29–40.
4. Ali, Z.; Fronczek, F. R.; Khan, I. A. Planta Med. 2008, 74, 178–181.
5. Manns, D. Planta Med. 1993, 59, 171–173.
6. Knapp, H.; Straubinger, M.; Fornari, S.; Oka, N.; Watanabe, N.; Winterhalter, P. J.
Agric. Food Chem. 1998, 46, 1966–1970.
7. Fan, W.; Tezuka, Y.; Ni, K. M.; Kadota, S. Chem. Pharm. Bull. 2001, 49, 396–401.
8. Ma, G.; Li, W.; Dou, D.; Chang, X.; Bai, H.; Satou, T.; Li, J.; Sun, D.; Kang, T.;
Nikaido, T.; Koike, K. Chem. Pharm. Bull. 2006, 54, 1229–1233.
9. Yoshikawa, M.; Nakamura, S.; Li, X.; Matsuda, H. Chem. Pharm. Bull. 2008, 5,
695–700.
ꢀ1
~
(CH3)2C), 12.7 (1C, CH3C). IR (ATR):
m
¼ 2956 cm (w), 1743 (m), 1729 (m),
1433 (w), 1369 (m), 1210 (s), 1166 (m), 1032 (s), 962 (m), 905 (m), 824 (w),
600 (m), 559 (w). UV–vis (MeOH): kmax (lg ) = 202 nm (4.05). MS (ESI): m/z (%):
565 (100) [M+Na]+, 566 (26), 567 (6). HRMS (ESI): calcd C26H42O12N [M+NH4]+:
e
10. Ghosh, P.; Sil, P.; Das, S.; Thakur, S.; Kokke, W. C. M. C. J. Nat. Prod. 1991, 54,
1389–1393.
560.2702, found: 560.2708. ½ ꢁ ꢀ24.5 (c 1.0, acetone). CD (TFE): kmax
a 2D5
11. Zdero, C.; Bohlmann, F.; Solomon, J. Phytochemistry 1988, 27, 891–897.
12. Northcote, P. T.; Andersen, R. J. J. Am. Chem. Soc. 1989, 111, 6276–6280.
13. Hong, B.-C.; Hong, J.-H.; Tsai, Y.-C. Angew. Chem. 1998, 110, 482–484; Hong,
B.-C.; Hong, J.-H.; Tsai, Y.-C. Angew. Chem., Int. Ed. 1998, 37, 468–470.
14. Corey, E. J.; Snider, B. B. J. Am. Chem. Soc. 1972, 94, 2548–2550.
15. Yamamoto, Y.; Asao, N. Chem. Rev. 1993, 93, 2207–2293.
16. Depew, K. M.; Danishefsky, S. J.; Rosen, N.; Sepp-Lorenzino, L. J. Am. Chem. Soc.
1996, 118, 12463–12464.
(
D
e
) = 192 (ꢀ39.40), 208 nm (ꢀ5.65 molꢀ1 dm3 cmꢀ1).
28. Satgé, C.; Le Bras, J.; Hénin, F.; Muzart, J. Tetrahedron 2005, 61, 8405–8409.
29. X-ray structure analysis of the ethanol solvate of pentaacetylrosiridin [(4S)-
14]. Crystal data: C28H44O13, monoclinic, P21, a = 11.8096(5), b = 7.4452(4),
c = 17.3830(6) Å, b = 90.394(2)°, Z = 2, T = 100 K.
0.3 ꢂ 0.2 ꢂ 0.04 mm was used to record a total of 20,498 data to 2h (max)
144° (99.9% complete to 135°) using Cu K radiation on an Oxford Diffraction
A
colorless plate
a
Nova O diffractometer. The structure was refined using the program SHELXL-97
(G.M. Sheldrick, University of Göttingen, Germany) to wR2 0.073, R1 0.029 (all
data) for 5390 independent data and 380 parameters. The ethanol molecule
was disordered over two positions. The Flack parameter refined to 0.06 (10),
thus determining the absolute configuration on the basis of the anomalous
dispersion of oxygen. Crystallographic data (excluding structure factors) have
been deposited with the Cambridge Crystallographic Data Centre as
supplementary publication nos. CCDC-691291. Copies of the data can be
obtained, free of charge, on application to CCDC, 12 Union Road, Cambridge
CB2 1EZ, UK (fax: +44-(0)1223-336033 or e-mail: deposit@ccdc.camac.uk).
17. Naruta, Y.; Nishigaichi, Y.; Maruyama, K. Org. Synth. 1993, 71, 118–124.
18. Harrowven, D. C.; Guy, I. L. Chem. Commun. 2004, 1968–1969.
19. Characterization of rac-1 and (ꢀ)-1: Rf (PE/EtOAc, 1:1) = 0.17. 1H NMR
(400 MHz, CDCl3): d = 5.67–5.62 (m, 1H, CHCH2OH), 5.13–5.09 (m, 1H,
(CH3)2CCH), 4.24–4.15 (m, 2H, CH2OH), 4.02–3.99 (m, 1H, CHOH), 2.28–2.19
(m, 3H, CH2CHOH, OH), 2.07 (br, 1H, OH), 1.73 (d, 4J = 1.1 Hz, 3H, (CH3)2C), 1.67
(m, 3H, CCH3), 1.64 (s, 3H, (CH3)2C). 13C NMR (100 MHz, CDCl3): d = 140.2 (1C,
CH3C), 135.0 (1C, (CH3)2C), 124.5 (1C, CHCH2OH), 119.8 (1C, (CH3)2CCH), 76.4
(1C, CHOH), 59.0 (1C, CH2OH), 34.1 (1C, CH2CHOH), 25.8 (1C, (CH3)2C), 18.0 (1C,
~
(CH3)2C), 12.1 (1C, CH3C). IR (ATR):
m
¼ 3319 cmꢀ1 (br, m), 2968 (w), 2915 (m),