Intermolecular O-H insertion reactions of L-tartrate derived α-diazo ketones: Synthesis of xylulose derivatives

Article abstract of DOI:10.1055/s-2000-6338

BF₃·OEt₂ or Ru-catalyzed intermolecular O-H insertion reactions of L- tartrate derived α-diazo ketones have given rise to a new synthesis of xylulose derivatives.

Full text of DOI:10.1055/s-2000-6338

352
SHORT PAPER
Intermolecular O-H Insertion Reactions of L-Tartrate Derived
α-Diazo Ketones: Synthesis of Xylulose Derivatives
Saumitra Sengupta,* Debasis Das
Department of Chemistry, Jadavpur University, Calcutta-700 032, India
Received 1 July 1999; revised 22 November 1999
5
systems and found that RuCl2(PPh3)3 or BF3∑OEt2 are
much better mediators for these reactions producing 6a, b
in 52-60% yields (Scheme 2, Table). RuCl2(PPh3)3 and
BF3∑OEt2 were also found quite effective in catalyzing in-
termolecular S-H insertion reactions of 5a, b with PhSH
to give the thioxylulonate derivatives 7a, b in 52-65%
yields. On the other hand, O-H insertion reactions of 5a,
b to HOAc was best carried out with Cu(OAc)2 as the cat-
alyst to produce the O-acetyl xylulonates 8a, b in 63-65%
yields (Table). Unfortunately, intermolecular N-H inser-
tion reactions of 5a, b with H2NCO2Et or H2NTos have so
far failed under a variety of conditions.
Abstract: BF3∑OEt2 or Ru-catalyzed intermolecular O-H insertion
reactions of L-tartrate derived a-diazo ketones have given rise to a
new synthesis of xylulose derivatives.
Key words: tartaric acid, a-diazo ketone, insertion reactions, xylu-
lose
In a synthetic study towards syributins and secosyrins,1
the major coproducts of syringolide elicitors isolated from
Pseudomonas syringae, we required the xylulose deriva-
tive 1 as the key retrosynthetic precursor. Although 1
could be potentially available via O-acylation reaction of
a suitably protected xylulonate derivative, the high cost of
preparing such derivatives from xylulose forced us to seek
for alternate cost-effective pathways. Towards this end
and based on reports of O-H insertion reactions of a few
carbohydrate derived a-diazo ketones to HOAc,2 we now
describe a facile synthetic strategy for 1 and other xylu-
lose derivatives via intermolecular O-H insertion reaction
of tartrate derived a-diazo ketones (e.g. 2, Scheme 1).
Scheme 2
Having found the optimum conditions for intermolecular
O-H insertion to 5, we turned towards our original goal,
i.e., to synthesize the syributin and secosyrin retrosynthet-
ic precursor 1. This was eventually achieved via
Cu(OAc)2-catalyzed insertion reaction of 5b with the ma-
lonic acid half ester 9 in dichloromethane which produced
ent-1 (P = Bz) in 45% yield (Scheme 3).
Scheme 1
While the absolute configurations in syributins and seco-
syrins required the D-tartrate derived a-diazo ketone 2, in
this work we used the cheaper L-tartrate derived a-diazo
ketones 5a, b as models. The latter were prepared in a few
steps from L-tartaric acid. Thus, one-pot di-O-acylation
and anhydride formation gave the anhydrides 3a and 3b,
which upon ring opening with methanol produced the half
esters 4a, and b,3 respectively, in near quantitative yields.
Acid chloride formation (SOCl2, benzene, room tempera-
ture) followed by treatment with excess diazo methane
then gave the a-diazo ketones 5a, b in 50-52% yields
(Scheme 2). Intermolecular O-H insertion reactions to 5a,
b were first studied with methanol using Rh2(OAc)4 as the
catalyst4 which while giving rise to the desired xylu-
lonates 6a, b (25-30%), however, led to a number of side
products which were difficult to separate from the desired
adducts. In view of this, we searched for milder catalyst
Scheme 3
In conclusion, we have described a short chiral pool based
synthesis of xylulose derivatives, en route syributins and
secosyrins, via intermolecular O-H insertion reactions to
tartrate derived a-diazo ketones. It also transpires from the
Synthesis 2000, No. 3, 352–354 ISSN 0039-7881 © Thieme Stuttgart · New York

SHORT PAPER
Intermolecular O-H Insertion Reactions of L-Tartrate Derived a-Diazo Ketones
353
and the aqueous portion was extracted with Et2O (2 ¥ 20 mL). The
combined organic layer was dried and evaporated under reduced
pressure to give the crude a-diazo ketones 5a, b which were purified
by column chromatography over silica gel (10% EtOAc in petro-
leum ether).
above study that milder catalysts like RuCl2(PPh3)3 or
BF3∑OEt2 may be better mediators over Rh2(OAc)4 for X-
H insertion reactions with highly oxygenated a-diazo ke-
tones.
(2R,3R)-Methyl 5-Diazo-4-oxo-2,3-dipivaloyloxypentanoate
(5a)
All the mps are uncorrected. IR spectra were taken on a Perkin Elm-
er R-297 spectrometer. 1H and 13C NMR spectra were recorded in
CDCl3 on JEOL FX-100 (100MHz) and Bruker DPX200 (200MHz)
instruments and are reported ppm scale. Optical rotations were mea-
sured on a JASCODIP-360 polarimeter. Column chromatography
were performed on silica gel (60-120). Petroleum ether refers to the
fraction boiling at 60-80 °C.
Yield: 1.80 g (50%); oil
[a]D20 +20.9 (c = 8, CHCl3)
IR (neat): n = 2986-2960 (br), 2880, 2120, 1750, 1730, 1635, 1450,
1360 cm-1.
1H NMR (CDCl3): d = 1.30 (s, 9H), 1.32 (s, 9H), 3.72 (s, 3H), 5.48
(s, 1H), 5.54 (d, 1H, J = 3.3 Hz), 5.68 (d, 1H, J = 3.3 Hz)
a-Diazo Ketones 5a, b; General Procedure
Anal: C16H24N2O7 (356.42): Calc C, 53.94; H, 6.73; N, 7.89. Found:
C, 53.31; H, 6.67; N, 8.12.
A mixture of SOCl2 (8.35 g, 5.0 mL, 70 mmol) and O,O-diprotected
tartaric acid monomethyl ester 43 (10 mmol) was stirred for 1.5-2
h at r.t. All volatiles were then removed under reduced pressure and
the acid chloride thus obtained was dissolved in CH2Cl2 (10 mL)
and added to an ice cold ethereal solution of CH2N2, [CAUTION:
Highly toxic; prepared from nitrosomethyl urea (5.5 g) and KOH
(3.0 g) in H2O (10 mL) and Et2O (50 mL)],6 over a period of 20 min.
The mixture was then allowed to reach ambient temperatures and
the excess CH2N2 was destroyed with a few drops of HOAc. Aq
NaHCO3 (10%, 20 mL) was then added, the Et2O layer separated
(2R,3R)-Methyl 2,3-Bis(benzoyloxy)-5-diazo-4-oxopentanoate
(5b)
Yield: 2.10 g (52%); mp 107-108∞C (EtOAc/ petroleum ether)
[a]D20 -27.9 (c = 4.7, CHCl3)
IR (Nujol): n = 2960-2940 (br), 2120, 1720, 1625, 1450, 1370
cm-1.
Table Xylulose Derivatives 6-8 Prepared via X-H Insertion Reactions of a-Diazo Ketones 5 (Scheme 2)
a-Diazo
Ketone
X-H
Cata-
lysta
Prod-
uct
Yield
(%)
Mpb [a]2D0
(oC) (c, CHCl3) Formulac
Molecular IR (CHCl3)
n (cm-1)
1H NMR (CDCl3 / TMS)
d, J (Hz)
5a
MeOH
A
6a
53
58- -18.5
C17H28O8
(360.03)
3050, 2980, 1.21 (s, 9 H), 1.24 (s, 9 H), 3.35 (s, 3 H ),
59
(2.0)
1740, 1420
3.75 (s, 3 H), 4.15 (AB q, 2 H, J = 17.4),
5.74 (d, 1 H, J = 2.7), 5.81 (d, 1 H, J =
2.7)
5a
5b
MeOH
MeOH
B
A
6a
6b
57
60
-
-
-
-
-
oil
-54.3
(0.9)
C21H20O8
(400.38)
3060, 2980, 3.45 (s, 3 H), 3.77 (s, 3 H), 4.22 (s, 2 H),
1735 (br), 6.15 (d, 1 H, J = 2.8), 6.18 (d, 1 H, J =
1600, 1585, 2.8), 7.45-7.60 (m, 6 H), 8.04-8.10 (m,
1490, 1450
4 H)
5b
5a
MeOH
PhSH
B
A
6b
7a
52
57
-
-
-
-
-
oil
-17.2
(2.3)
C22H30O7S 2950, 1750, 1.21 (s, 9 H), 1.25 (s, 9 H), 3.72 (s, 3 H),
(438.45)
1730 (br),
1470, 1420
3.81 (s, 2 H), 5.58 (d, 1 H, J = 1.6), 5.89
(d, 1 H, J = 1.6), 7.29-7.54 (m, 5 H)
5a
5b
PhSH
PhSH
B
A
7a
7b
52
65
-
-
-
-
-
oil
-46.4
(2.2)
C26H22O7S 3060, 2980, 3.72 (s, 3 H), 3.90 (s, 2 H), 6.11 (d, 1 H,
(478.42)
1730 (br),
1600, 1580
J = 2.7), 6.21 (d, 1 H, J = 2.7), 7.20-7.80
(m, 11 H), 8.10-8.40 (m, 4H)
5b
5a
PhSH
B
C
7b
8a
56
63
-
-
-
-
-
HOAc
oil
-19.2
(1.2)
C18H28O9
(388.31)
3050, 2980, 1.24 (s, 9 H), 1.26 (s, 9 H), 2.16 (s, 3 H),
1735 (br),
3.74 (s, 3 H), 4.83 (s, 2 H), 5.55 (d, 1 H,
1450, 1420
J = 2.5), 5.76 (d, 1H, J = 2.5)
5b
HOAc
C
8b
65
87- -33.4
88 (0.80)
C22H20O9 3050, 2980, 2.03 (s, 3 H), 3.69 (s, 3 H), 4.92 (m, 2 H),
(428.29)
1730 (br),
5.96 (d, 1 H, J = 1.9), 6.10 (d, 1 H, J =
1.9), 7.30-7.48 (m, 6 H), 7.90-8.15 (m,
4 H)
1450, 1420
a A = RuCl2(PPh3)3; B = BF3◊OEt2; C = Cu(OAc)2
b Recrystallization from EtOAc/petroleum ether.
c Satisfactory microanalyses obtained: C 0.10, H 0.37.
Synthesis 2000, No. 3, 352–354 ISSN 0039-7881 © Thieme Stuttgart · New York

354
S. Sengupta, D. Das
SHORT PAPER
1H NMR (CDCl3): d = 3.74 (s, 3H), 5.66 (s, 1H), 5.97 (d, 1H,
J = 2.6 Hz), 6.04 (d, 1H, J = 2.6 Hz), 7.43-7.65 (m, 6H), 8.07-8.13
(m, 4H).
column chromatography (15-25% EtOAc in petroleum ether) to
give 0.11 g (45%) of ent-1 (P = Bz) as an oil.
[a]D20 -28.7 (c = 1.2, CHCl3)
IR (CHCl3): n = 3050, 2920, 1740 (br), 1450 cm-1.
1H NMR (CDCl3): d = 1.27 (t, 3H, J = 7.1 Hz), 3.47 (s, 2H), 3.78 (s,
3H), 4.19 (q, 2H, J = 7.1 Hz), 5.07 (AB q, 2H, J = 17.4 Hz), 5.99 (d,
1H, J = 2.8 Hz), 6.13 (d, 1H, J = 2.8 Hz), 7.46-7.66 (m, 6H), 8.08-
8.13 (m, 4H).
13C NMR (CDCl3): d = 13.9, 40.9, 53.1, 61.7, 67.3, 71.4, 75.6,
127.9, 128.4, 128.6, 130.0, 130.1, 133.6, 133.8, 134.2, 165.1, 165.4,
165.9, 166.5, 196.4.
Anal: C20H16N2O7 (396.39): Calc C, 60.61; H, 4.04; N, 7.1. Found:
C, 60.58; H, 4.01; N, 7.0.
RuCl2(PPh3)3-Catalyzed O-H and S-H Insertion Reactions to a-
Diazo Ketones 5a, b
A solution of the a-diazo ketones 5a, b (1.0 mmol) in benzene (2
mL) was added dropwise over 2 h to a refluxing solution of MeOH
(0.5 mL) or PhSH (0.5 mL) in benzene (5 mL) containing catalytic
amounts of RuCl2(PPh3)3 (0.02-0.05 g). After the addition was
complete, the solution was refluxed for an additional 15 min. after
which the solvent was removed under reduced pressure. The residue
was diluted with CH2Cl2 (20 mL) and washed with H2O. The organ-
ic layer was dried, evaporated under reduced pressure and the crude
products purified by column chromatography over silica gel (5-
10% EtOAc in petroleum ether) to give 6a, b and 7a, b (Table).
Anal: C25H24O11 (500.33): Calc C, 60.00; H, 4.80. Found: C, 59.95;
H, 4.83.
Acknowledgement
DST (SP/S1/G-14/97) and JU (SRF to DD) are thanked for financial
support.
BF3∑OEt2-Catalyzed O-H and S-H Insertion Reactions to a-
Diazo Ketones 5a, b
BF3∑OEt2 (7.0-14.0 mg) was added to a mixture of the diazoke-
tones 5a or 5b (1.0 mmol) and MeOH (5 mL) [or PhSH (5 mL)] in
CH2Cl2 (5 mL) at r.t. The mixture was then warmed at 40 ∞C for 2
h until evolution of N2 had ceased. The mixture was diluted with
CH2Cl2 (20 mL) and washed with aq NaHCO3 (10%, 10 mL) (10%
aq NaOH for reaction with PhSH), dried and concentrated under re-
duced pressure. The crude products were purified by column chro-
matography over silica gel (5-10% EtOAc in petroleum ether) to
give 6a, b and 7a, b (Table).
References
(1) Midland, S. L.; Keen, N. T.; Sims, J. J. J. Org. Chem. 1995,
60, 1118.
Honda, T.; Mizutani, H.; Kanai, K. J. Org. Chem. 1996, 61,
9374.
Yu, P.; Yang, Y.; Zhang, Z. Y.; Mak, T. C. W.; Wong, H. N.
C. J. Org. Chem. 1997, 62, 6359.
Mukai, C.; Moharram, S. M.; Azukizawa, S.; Hanaoka, H. J.
Org. Chem. 1997, 62, 8095.
Cu(OAc)2-Catalyzed Insertion Reactions of a-Diazo Ketones
5a, b with HOAc
Carda, M.; Castillo, E.; Rodriguez, S.; Falomir, E.; Marco, J.
A. Tetrahedron Lett. 1998, 39, 8895.
To a solution of the a-diazo ketones 5a, b (1.0 mmol) in HOAc (2
mL) was added Cu(OAc)2 (2.0-3.0 mg) and the solution heated to
70-80 ∞C when rapid evolution of N2 gas was observed. After N2
evolution ceased (15 min), the mixture was poured into H2O (10
mL). The aqueous layer was extracted with CH2Cl2 (2 ¥ 20 mL)
and the organic layer washed with aq NaHCO3 (10%, 2 ¥ 10 mL),
dried and concentrated to a syrup which was purified by silica gel
chromatography (15-25% EtOAc in petroleum ether) to give 8a, b
(Table).
(2) Bestmann, H. J.; Moll, C. Synlett 1996, 729.
Bestmann, H. J.; Schmiechen, R. Chem. Ber. 1961, 94, 751.
Wolfrom, M. L.; Thompson, A.; Evans, E. F. J. Am. Chem.
Soc. 1945, 67, 1793.
Wolfrom, M. L.; Waisbrot, S. W.; Brown, R. L. J. Am. Chem.
Soc. 1942 64, 2329.
(3) Duhamel, L.; Herman, T.; Angiband, P. Synth. Commun.
1992, 22, 735.
Lucas, H. J.; Baumgarten, W. J. Am. Chem. Soc. 1941, 63,
1653.
(4) Miller, D. J.; Moody, C. J. Tetrahedron 1995, 51, 10811.
(5) Sengupta, S.; Das, D.; Sen Sarma, D. Tetrahedron Lett. 1996,
37, 8815.
(2R,3R)-Methyl 2,3-Dibenzoyloxy-5-(1-ethoxycarbonylace-
toxy)-4-oxopentanoate (ent-1)
Cu(OAc)2 (3.0 mg) was added to a solution of the a-diazo ketone 5b
(0.20 g, 0.5 mmol) and malonic acid monoethyl ester (1.0 g, 7.5
mmol) in CH2Cl2 (1 mL). The solution was warmed to 40∞C and af-
ter N2 evolution had ceased, the mixture was poured into H2O (10
mL). The aqueous layer was extracted with CH2Cl2 (2 ¥ 20 mL)
and the organic layer washed with aq NaHCO3 (10%, 2 ¥ 10 mL),
dried and concentrated to a syrup which was purified by silica gel
(6) Arndt, F. Org. Synth. Coll. Vol. II 1943, 165.
Article Identifier:
1437-210X,E;2000,0,03,0352,0354,ftx,en;H05799SS.pdf
Synthesis 2000, No. 3, 352–354 ISSN 0039-7881 © Thieme Stuttgart · New York