Diastereoselective synthesis of 1-allyl and 1,2-bis(allyl)-1,2- diols: Versatile synthons for substituted tetrahydrofuran derivatives

Article abstract of DOI:10.1055/s-2001-16774

2-Hydroxyketones and 2-ketoaldehydes undergo indium mediated highly diastereoselective mono and bis- allylation reactions to give respective 1-allyl 2a-c and 1,2-bis (allyl)- 7a-c 1,2 diols. 2a undergoes I₂ / NaHCO₃ and m-CPBA mediat

Full text of DOI:10.1055/s-2001-16774

LETTER
1431
Diastereoselective Synthesis of 1-Allyl and 1,2-bis(Allyl)-1,2- diols:
Versatile Synthons For Substituted Tetrahydrofuran Derivatives
Subodh Kumar,* Pervinder Kaur, Swapandeep Singh Chimni, Palwinder Singh
Department of Chemistry, Guru Nanak Dev University, Amritsar -143 005, India
E-mail: subodh.kumar@angelfire.com
Received 1 June 2001
of COSY and NOE experiments on its cyclised products 4
and 5. This procedure offers a convenient alternative to
similar allylations performed through tetraallyltin10. Sim-
ilarly, -hydroxyketone 1b undergoes highly diastereose-
Abstract: 2-Hydroxyketones and 2-ketoaldehydes undergo indium
mediated highly diastereoselective mono and bis- allylation reac-
tions to give respective 1-allyl 2a-c and 1,2-bis (allyl)- 7a-c 1,2 di-
ols. 2a undergoes I2
/ NaHCO3 and m-CPBA mediated
diastereoselective intramolecular cyclizations to provide respective lective allylation to provide 2b, M+ m/z 234 but in case of
2c, M+ m/z 196, de is lowered to 95% (Scheme 1). The
(2S*, 3R*, 5S*)-2,3-diphenyl-4-hydroxy-5-iodo methyltetrahydro-
furan 4a and (2S*, 3R*, 5R*)-2,3-diphenyl-4-hydroxy-5-hy-
stereochemistries for 2b and 2c have been defined in anal-
droxymethyl tetrahydrofuran 5b as major product.
ogy with 2a.
Key words: diastereoselective, allylation, cyclisation, hydroxyke-
tones, ketoaldehydes
The stereoselective 1,2-additions especially allylation to
carbonyl compounds continue to have central position in
asymmetric organic synthesis1. The stereoselectivity
stems from the chelated intermediates and is considerably
affected by the choice of the solvents, different additives
Scheme 1
and pH of the reaction medium along with the nature of
the substituent present on the carbonyl and allyl substrate.
In recent years, the indium2 mediated allylations have
The solution of 2a in dry CH3CN containing suspended
shown that the presence of water does not inhibit the op-
eration of chelation control and often exceeds than that at-
tainable with corresponding magnesium, cerium or
chromium reagents in anhydrous media3. -Hydroxy/
alkoxy/ amino moiety in carboxaldehydes4 and
cyclohexanone5 lead to considerable -facial discrimina-
tion but thioethers lead to poor stereoselectivity. Howev-
er, the acyclic hydroxy ketones6 have been less studied
and generally show poor stereoselectivity. Further, indi-
um mediated allylations of 1,2-dioxo compounds give
mono allylated hydroxy ketones7 or diallylated products8
with poor diastereoselectivity. Here, we unravel both
these limitations and report that acyclic 2-hydroxyketones
undergo diastereoselective monoallylation and 2-ketoal-
dehydes undergo diastereoselective diallylation to pro-
vide respective 1-allyl (2a-c) and 1,2-bisallyl- (7a-c) 1,2-
diols. 2a undergoes diastereoselective cyclisations to tet-
rahydrofuran derivatives 4 and 5.
NaHCO3 (3 equiv) was stirred at 30 °C for 5 min followed
by addition of iodine (3 equiv) and stirring for 72 hours.
The reaction mixture after workup and chromatography
gave two isomeric products (4:1 ratio) with M+ m/z 380
(Scheme 2). In case of fast moving component11 (minor),
the irradiation of singlet at 5.29 (2-H) shows positive
NOE signals at 4.6 (5-H), 2.78(4-Ha) and 7.04, 7.38
(ArH) and irradiation of AB quartet at 2.78 shows posi-
tive signals at 2.48(4-Hb), 4.61(5-H), 5.29 (2-H) and
7.38 (ArH). These observations show that two aryl rings
are on the opposite side of furan ring and 2-H and 5-H are
on the same side of tetrahydrofuran ring and has been as-
signed the structure 5a. In case of slow moving (major)
component, irradiation of singlet at 5.53 (2-H) does not
show NOE for H-5 ( 4.55 - 4.60) and has been assigned
the structure (2S*, 3R*, 5S*)-2,3-diphenyl-4-hydroxy-5-
iodo methyltetrahydrofuran 4a. The lowering of reaction
temperature increases the overall yield of products but
does not affect the diastereoselectivity which is only mar-
ginally affected by use of CH2Cl2 or toluene as solvents.
The solution of 1a, allyl bromide and indium metal (sus-
pension) (1: 1.5: 1) in THF-H2O (2: 1) on stirring at
30±1 °C for 6-8 h, after HCl hydrolysis, CH2Cl2 extrac-
tion and chromatography provides 2a (92%)9, mp 95 °C
(Lit.10 m.p. 96-97 °C). On performing the reaction under
Grignard conditions at reflux temperature, the second di-
astereomer 3 is also formed but again formation of 2a
through a chelate intermediate is preferred (2a : 3:: 9: 1).
The stereochemistry of 2a has been defined on the basis
Stirring of 2a with m-CPBA in CHCl3 at 30 °C for 24
hours gave a mixture of two diastereomers12 4b and 5b
(16: 84). However, on lowering reaction temperature to
0 °C, the yield of minor component 4b is increased
(Scheme 2) and use of CH3CN as solvent leads to complex
mixure. Therefore, both I2 / NaHCO3 and m-CPBA medi-
Synlett 2001, No. 9, 1431–1433 ISSN 0936-5214 © Thieme Stuttgart · New York

1432
S. Kumar et al.
LETTER
Acknowledgement
We thank CSIR, New Delhi for financial assistance [01(1530)/98].
References and Notes
(1) (a) Roush,W.R. In Comprehensive organic synthesis Ed. C.
Heathcock, Pergamon Press, Oxford, 1991,Vol2. p.1.
(b) Yamamoto, Y.; Asao, N. Chem. Rev. 1993, 93, 2007.
(2) (a) Li, C.J. Chem. Rev. 1993, 93, 2023. (b) Li, C.J.
Tetrahedron 1996, 52, 5643. Li, C.J.; Chan, T.H. Tetrahedron
1999, 55, 11149. (d)). Li, C.J.; Chan, T.H. "Organic reaction
in aqueous media" John Wiley and sons., Inc., New York,
1997. (e).Lubineau, J. A.; Y. Queneau, Synthesis 1994, 741.
(3) (c) Paquette, L.A.; Lobben, P.C. J. Am. Chem. Soc., 1996,
118, 1917.
(4) (a) Chan, T.-H.; Lee, M.C. J. Org. Chem. 1995, 60, 4228.
(b) Crao, J.; Houter, R.; Gordon, D.M.; Whitesides, G.M. J.
Org. Chem. 1994, 59, 3714. (c) Paquette, L.A.; Mitzel, T.M.
J. Am. Chem. Soc. 1996, 118, 1931. (d) Paquette, L.A.; Mitzel,
T.M. J. Org. Chem. 1996, 61, 8799. (e) Paquette, L.A.; Mitzel,
T.M.; Isaac, M.B.; Crasto, C.F.; Schomer, W.W. J. Org.
Chem. 1997, 62, 4293.
(5) Paquette, L.A.; Lobben, P.C. J. Org. Chem. 1998, 63, 5604.
(b) Lobben, P.C.; Paquette, L.A. J. Org. Chem. 1998, 63,
6990.
(6) Carda, M.; Castillo, E.; Rodriguez, S.; Falomiv, E.; Marco,
J.A. Tetrahedron Letters 1998, 39, 8895. (b) Carda, M.;
Castillo, E.; Rodriguez, S.; Muaga, J.; J.A. Marco,
Tetrahedron Asymmetry 1998, 9, 1117. (c) Loh, T.; Ho, D.S.;
Chua, G.; Sim, K. Synlett 1997, 563.
(7) (a) Nair, V.; Jayan, C. N. Tetrahedron Letters 2000, 41, 1091.
(b)Yang, Y.; Wang, M.; Wang, D. J. Chem. Soc. Chem.
Commun. 1997, 1651. (c) Asao, N.; Liu, P. and Maruoka, K.
Angew. Chem. Int. Ed. Engl. 1997, 36, 2507.
ated cyclizations on lowering of temperature result in
higher ratio of 4 over 5.
Scheme 2
The allylation of phenylglyoxal (6a) with allyl bromide
and indium metal (1: 3: 2) under above conditions gave di-
allylated product 7a, (96%), M+ m/z 218. 1H NMR of the
crude reaction mixture or the pure compound show pres-
ence of only one diastereomer and formation of second di-
astereomer could not be observed. On performing the
reaction by using one equivalent of indium metal, only di-
allylated product 7a is formed and part of phenylglyoxal
remains unreacted. The formation of monoallylated prod-
uct 8 is not observed. The earlier attempts on allylation of
6a have lead to formation of 8 or its mixture with 7a in
5:12 ratio in overall 17% yield13. In order to assess the
generality of the process, the reaction has been studied
with 6b and 6c (Scheme 3). These reactions constitute
first examples, where keto aldehydes undergo diastereo-
selective bis allylation.
(8) V. Cere, F. Peri, S. Pollicino and A. Ricci. Synlett 1999, 1585.
(9) General Procedure: The carbonyl compound 1 (0.5 mmol),
allyl bromide (0.75 mmol), indium metal (0.5 mmol) were
taken in THF - H2O (2:1) mixture (20 mL) and the reaction
mixture was stirred at 30±1 °C till the indium metal dissolved.
The turbid reaction mixture was treated with dil. HCl and was
extracted with CHCl3. The solvent was distilled off and the
residue was column chromatographed (silica gel, 60-120
mesh) to isolate allyl addition product.
2a: (80%), mp 94-5 °C; M+ m/z 237 (M+ -OH); 1H NMR
(CDCl3): 2.37 (s, 1H, OH, exchanges with D2O), 2.48(s, 1H,
exchanges with D2O, OH),, 2.73 (dd, J1 = 14.1Hz, J2 = 8.6Hz,
1H, 1/2CH2), 2.93(dd, J1 = 14.1Hz, J2 = 5.4 Hz, 1H, 1/2 CH2),
4.77(s, 1H, CH), 5.05-5.19 (m, 2H, =CH2), 5.45 - 5.61 (m,
1H, =CH), 6.95 - 7.24 (m, 10H, ArH); 13C NMR (CDCl3):
42.47 (-ve, CH2), 78.25(ab, C), 80.36(+ve, CH), 119.57 (-ve,
CH2), 126.49(+ve, CH), 126.78(+ve, CH), 127.33(+ve, CH),
127.49(+ve, CH), 127.76 (+ve, CH), 133.31(+ve, CH), 139.35
(ab, C), 141.55(ab, C).
Scheme 3
Therefore, 2-hydroxyketones and 2-ketoaldehydes under-
go indium mediated highly diastereoselective mono- and
bis(allylation) reactions to give 1-allyl-(2a-c) and 1,2-
bis(allyl)- (7a-c) 1,2-diols, respectively. 2a undergoes I2 /
NaHCO3 and m-CPBA mediated diastereoselective in-
tramolecular cyclizations to give diastereomerically two
different tetrahydrofurans (4/5) as major products. The ef-
fect of various substituents in the reactants - ketones and
allyl halides on diastereoselectvity is under investigation.
3a: (10%), mp 90 °C, M+ m/z 254 (M+); 1H NMR (CDCl3):
1.58 (b, 1H, OH), 2.93(dd, J1 = 13.8Hz, J2 = 7.4Hz, 1H),
3.13(dd, J1 = 13.8Hz, J2 = 7.4 Hz, 1H), 4.05 (1H, OH), 4.98 (s,
1H, CH), 5.06 - 5.15 (m, 2H, =CH2), 5.63 - 5.75 (m,
1H, =CH), 7.14 -7.74 (m, 10H, ArH).
2b (90%), liquid, M+ m/z 234(M+); 1H NMR (CDCl3): 1.25
(s, 1H, OH, exchanges with D2O), 1.48 (s,1H, OH, exchanges
with D2O), 2.70(dd, J1 = 14Hz, J2 = 8.1Hz, 1/2 CH2), 2.84 (dd,
J1 = 14Hz, J2 = 6.2 Hz, 1/2 CH2), 4.83 (s, 1H, CH), 5.11 - 5.20
(m, 2H, =CH2), 5.59 - 5.72 (m, 1H, =CH), 6.03 (d, J = 2.8Hz,
1H, =CH), 6.11(d, J1 = 2.8 Hz, 1H, =CH), 6.24(t, J = 2.8Hz,
1H, =CH), 6.25 (t, J = 2.8Hz, 1H, =CH), 7.28 (d, J = 2.8Hz,
1H, =CH), 7.29 (d, J = 2.8Hz, 1H, =CH); 13C NMR (CDCl3):
Synlett 2001, No. 9, 1431–1433 ISSN 0936-5214 © Thieme Stuttgart · New York

LETTER
Diastereoselective Synthesis of 1-Allyl and 1,2-bis(Allyl)-1,2- diols
1433
d 40.78 (-ve, CH2), 72.86 (ab, C), 76.07 (+ve, CH), 107.14
(+ve, CH), 107.68 (+ve, CH), 110.20 (+ve, CH), 119.52 (-ve,
CH2), 132.66 (+ve, CH), 141.68 (+ve, CH), 141.82 (+ve, CH),
152.8 (ab, C), 155.18 (ab, C).
125.41(+ve, CH), 126.68(+ve, CH), 127.31(+ve, CH),
128.38(+ve, CH), 128.40(+ve, CH), 134.97(ab, C), 142.38(ab,
C).
(12) 5b: (60%); m.p. 160 °C (CH2Cl2); M+ m/z 270(M+); 1H
NMR(CDCl3): 2.45 (dd, J1 = 9.4Hz, J2 = 2.2 Hz, 1H, 4-Hb),
2.84 (dd, J1 = 9.4Hz, J2 = 6.8 Hz, 1H, 4-Ha), 3.79 (dd, J1 = 7.6
Hz, J2 = 2.2 Hz, 1H, 5-CH2OH), 4.08 (dd, J1 = 7.6Hz, J2 = 1.6
Hz, 1H, 5 CH2OH), 4.49 - 4.73 (m, 1H, H-5), 5.19 (s, 1H, H-
2), 7.03 - 7.45 (m, 10H, ArH); 13C NMR (CDCl3): 45.03(-ve,
CH2), 63.28(-ve, CH2), 77.89(+ve, CH), 80.56(ab, C),
89.96(+ve, CH), 125.55(+ve, CH), 126.42(+ve, CH),
126.97(+ve, CH), 127.8(+ve, CH), 136.28(ab,C), 141.43(ab,
C).
(10) Yasuda, M.; Fujibayashi, T.; Baba, A. J. Org. Chem. 1998, 63,
6401.
(11) The assignement of signals is based on 1H-1H COSY and
HMQC studies. 4a: Lower Rf component: (80%); liquid; M+
m/z 380(M+); 1H NMR(CDCl3): 1.79 (bs, 1H, OH), 2.45 (dd,
J1 = 8.8Hz, J2 = 6.4Hz, 4-Ha), 2.62 (dd, J1 = 8.8Hz, J2 = 3.8 Hz,
H-4b), 3.51 (dd, J1 = 7Hz, J2 = 2.6Hz, 1H of 5-CH2I), 3.61 (dd,
J1 = 7Hz, J2 = 4Hz, 1H of 5-CH2I), 4.55 - 4.60 (m, 1H, H-5),
5.53 (s, 1H, H-2), 6.98 - 7.45 (m, 10H, ArH); 13C NMR
(CDCl3): 12.41(-ve, CH2), 49.20(-ve, CH2), 76.79(+ve, CH),
83.18(ab, C), 89.52(+ve, CH), 124.43(+ve, CH), 126.31(+ve,
CH), 126.57(+ve, CH), 128.05(+ve, CH), 128.62(+ve, CH),
135.15(ab, C), 144.46(ab, C).
(13) Masuyama, Y.; Tsunoda, T. and Kurusu, Y., Chem. Letters
1989, 1647.
5a: Higher Rf Component : (20%); M+ m/z 380; 1H
NMR(CDCl3): 2.48(dd, J1 = 9.2 Hz, J2 = 2.6 Hz, 4-Hb), 2.78
(dd, J1 = 9.2 HZ, J2 = 6 Hz, 4-Ha), 3.63 (d, J = 4.4 Hz, 2H, 5-
CH2I), 4.57 - 4.72 (m, 1H, 5-H), 5.29 (s, 1H, 2-H), 7.01 - 7.39
(m, 10H, ArH); 13C NMR (CDCl3): 10.25(-ve, CH2), 48.40(-
ve, CH2), 78.34(+ve, CH), 82.33(ab, C), 91.02(+ve, CH),
Article Identifier:
1437-2096,E;2001,0,09,1431,1433,ftx,en;D08401ST.pdf
Synlett 2001, No. 9, 1431–1433 ISSN 0936-5214 © Thieme Stuttgart · New York