The Retro-Michael Reaction of 1,5-Dicarbonyl Compounds: Scope and Limitation

Article abstract of DOI:10.1135/cccc19990107

Under catalysis of NaOH or KOH adsorbed on glass wool and by using steam distillation, (20R,S)-4,4,5,14-tetramethyl-18,19-dinor-13,17-seco-5β,8α,9β,10α,14β-cholestane-13,17-dione (1) and 3,14-dioxo-14,15-seco-5α-cholestan-15-al (4) gave good yield (>59 percent) of the corresponding tricyclic compounds (8a, 8b and 10a) via a retro-Michael reaction at 250 deg C. While 5-oxo-4-nor-3,5-secocholestan-3-oic acid (6) and ethyl 5-oxo-4-nor-3,5-secocholestan-3-oate (7) afforded low yield (<15 percent) of the retro-Michael cleavage products (12a, 12b) at the same conditions. Thus, the retro-Michael reaction worked well for 1,5-diketones and 1,5-keto aldehydes but gave poor yield for 1,5-keto esters and 1,5-keto acids.

Full text of DOI:10.1135/cccc19990107

Retro-Michael Reaction
107
THE RETRO-MICHAEL REACTION OF 1,5-DICARBONYL COMPOUNDS:
SCOPE AND LIMITATION
1,
Jian-Xin WANG and Tong-Shuang LI *
Department of Chemistry, Hebei University, Baoding 071002, Hebei Province, China;
1
e-mail: orgsyn@mail.hbu.edu.cn
Received Jun e 2, 1998
Accepted Novem ber 2, 1998
Un der catalysis of NaOH or KOH adsorbed on glass wool an d by usin g steam distillation ,
(20R,S)-4,4,5,14-tetram eth yl-18,19-din or-13,17-seco-5β,8α,9β,10α,14β-ch olestan e-13,17-dion e (1)
an d 3,14-dioxo-14,15-seco-5α-ch olestan -15-al (4) gave good yield (>59%) of th e correspon din g
tricyclic com poun ds (8a, 8b an d 10a) via a retro-Mich ael reaction at 250 °C. Wh ile 5-oxo-4-
n or-3,5-secoch olestan -3-oic acid (6) an d eth yl 5-oxo-4-n or-3,5-secoch olestan -3-oate (7) afforded
low yield (<15%) of th e retro-Mich ael cleavage products (12a, 12b) at th e sam e con dition s.
Th us, th e retro-Mich ael reaction worked well for 1,5-diketon es an d 1,5-keto aldeh ydes but
gave poor yield for 1,5-keto esters an d 1,5-keto acids.
Key w ord s: Retro-Mich ael reaction ; Tricyclic com poun ds; Dicarbon yl com poun ds; Steroids;
Terpen oids.
Meth ylated tricyclic terpan es are im portan t n ovel biom arkers recen tly dis-
covered from a bogh ead sam ple in Sh uich en g, western Guizh ou of Ch in a1.
In con n ection with our syn th esis of th is series of m eth ylated tricyclic terpa-
n es, th e retro-Mich ael reaction of 1,5-dicarbon yl com poun ds derived from
ch olestan e or dam m aran e is projected to be em ployed as a key step. Litera-
ture search sh ows th at th is reaction works well for arom atic 1,5-diketon es
in th e in let of m ass spectrom eter2. For alicyclic keton es, h owever, drastic
con dition s are n eeded an d lead to poor or m oderate yields3–5. Recen tly,
Albrech t et al. developed an im proved approach by usin g steam distillation
of 1,5-diketon es with sodium h ydroxide adsorbed on glass wool as a cata-
lyst an d obtain ed h igh yields of th e products6. Up to th e presen t tim e, th e
utilization of th is degradative m an n er in syn th esis h as been on ly lim ited to
1,5-diketon e com poun ds7. We report h erein th e in vestigation of th e scope
an d lim itation of retro-Mich ael reaction of 1,5-dicarbon yl com poun ds.
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Wang, Li:
EXPERIMENTAL
Meltin g poin ts were m easured on an XT4 Kofler h ot stage an d were un corrected. IR spectra
were recorded on a PE-983G spectrom eter as liquid film s by usin g CDCl3 as solven t; wave-
.
n um bers in cm –1 1H an d 13C NMR spectra were m easured on Bruker AM-400 or AC-80 spec-
trom eters by usin g TMS as in tern al stan dard an d CDCl3 as solven t un less oth erwise stated.
Ch em ical sh ifts are given in ppm (δ-scale), couplin g con stan ts (J) in Hz. Mass spectra were
determ in ed on a VG-7070E spectrom eter (EI, 70 eV). Th in -layer ch rom atograph y (TLC) was
perform ed on silica gel-60H (Merck). (20R,S)-4,4,5,14-Tetram eth yl-18,19-din or-13,17-seco-
5β,8α,9β,10α,14β-ch olestan e-13,17-dion e (1) was prepared from ch olesterol (2) accordin g to
literature8 in an overall yield of 31%. 14,15-Dioxo-14,15-seco-5α-ch olestan -3β-yl acetate (3)
an d 3,14-dioxo-14,15-seco-5α-ch olestan -15-al (4) were syn th esized from ch olesterol (2) in
five an d seven steps in overall yields of 20 an d 16%, respectively, as described by Li et al.9.
Ozon ization of ch olest-4-en -3-on e (5) accordin g to literature10 provided 5-oxo-4-
n or-3,5-secoch olestan -3-oic acid (6).
Eth yl 5-Oxo-4-n or-3,5-secoch olestan -3-oate11 (7)
To a solution of 6 (0.45 g, 1.1 m m ol) in DMSO (15 m l) was added potassium h ydroxide
(0.25 g, 4.5 m m ol) an d th en followed by eth yl iodide (0.19 m l, 0.36 g, 2.3 m m ol). Th e
solution was stirred at 60 °C for 2 h and after cooling, the mixture was poured into water (70 ml).
The solution was extracted with ether (2 × 40 ml) and CH2Cl2 (3 × 30 ml). The combined organic
ph ase was dried (MgSO4) an d evaporated to dryn ess. Th e residue was ch rom atograph ied on
silica gel with ligh t petroleum –eth er (8 : 1) as eluen t to afford th e title com poun d 7 (0.36 g,
75%) as a colourless oil. IR: 2 950, 2 835, 1 735, 1 700, 1 460, 1 420, 1 375, 1 295, 1 195,
930. 1H NMR (80 MHz): 0.72 s, 3 H (3 × H-18); 0.85 d, 6 H, J = 6.6 (3 × H-26 an d 3 × H-27);
0.90 d, 3 H, J = 5.4 (3 × H-21); 1.10 s, 3 H (3 × H-19); 1.24 t, 3 H, J = 7.1 (OCH2CH3); 4.11 q,
3 H, J = 7.1 (OCH2CH3). For C28H48O3 (432.7) calculated: 77.7% C, 11.2% H; foun d: 77.5% C,
11.5% H.
Gen eral Procedure for th e Retro-Mich ael Reaction
Th e catalyst was prepared by passin g a solution of 30% sodium (com poun ds 1, 3 an d 4) or
potassium (com poun ds 6 an d 7) h ydroxide th rough a colum n (20 × 2 cm ) loosely packed
with glass wool an d th en th e colum n was h eated by a tubular oven at 210 °C for 3 h . Steam
was successively in troduced to th e preh eatin g tube (210 °C), th e in let an d th e catalysis tube.
After stabilization of th e catalysis tube tem perature at 250 °C an d reach in g th e rate of con -
den sation of water to 5 m l/m in , th e startin g m aterial dissolved in sm all quan tity of eth er
was in jected in to th e in let. Th e rate an d th e tem perature of th e catalysis tube (250–260 °C)
was kept un til n o oil was appeared in th e con den ser. Th e obtain ed water solution was ex-
tracted with eth er (4 tim es) an d th e com bin ed extracts were dried (MgSO4) an d con cen trated
to give th e crude product. Th is was furth er separated by silica gel colum n ch rom atograph y.
Com poun d 1 (98.5 m g, 0.229 m m ol) afforded 4,4,5,14-trimethyl-des-D-5β,8α,9β,10α,14α-
androstan-13-one (8a; 37.2 m g, 57%) an d 4,4,5,14-trimethyl-des-D-5β,8α,9β,10α,14β-androstan-
13-one (8b; 9.6 m g, 16%). Com poun d 8a, m .p. 91–93 °C (colourless n eedles from eth an ol).
TLC: RF 0.33 (ligh t petroleum –eth er, 5 : 1), silica gel-60H. IR: 2 986, 2 957, 2 880, 1 708, 1 448,
1 378, 1 195, 1 175, 1 130, 965, 938. 1H NMR (80 MHz): 0.81 s, 3 H (Me-5β); 0.93 s, 6 H
(Me-4α an d Me-4β); 0.98 d, 3 H, J(Me,14) = 6.5 (Me-14α). 1H NMR (400 MHz, C6D6):
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Retro-Michael Reaction
109
0.773 s, 3 H (Me-4α); 0.794 s, 3 H (Me-4β); 0.874 s, 3 H (Me-5β); 1.058 d, 3 H, J(Me,14) = 6.5
(Me-14α). 13C NMR (100 MHz, C6D6): 11.56 (q), 14.90 (q), 22.53 (q), 22.65 (t), 25.03 (t),
25.57 (q), 26.83 (t), 31.44 (t), 32.63 (t), 36.28 (s), 37.27 (t), 38.52 (s), 41.21 (d), 41.27 (t),
43.68 (d), 49.50 (d), 50.30 (d), 210.22 (s). MS, m/z (%): 262 (M+, 94), 247 (6), 205 (9), 190 (6),
177 (100), 149 (26), 135 (15), 121 (19), 107 (17), 95 (21), 81 (23). For C18H30O (262.4) calcu-
lated: 82.4% C, 11.5% H; foun d: 82.1% C, 11.8% H. Com poun d 8b , m .p. 177–180 °C
(colourless plates from eth an ol). TLC: RF 0.26 (ligh t petroleum –eth er, 5 : 1). IR: 2 928, 2 860,
1 710, 1 460, 1 430, 1 375, 1 010, 760, 730. 1H NMR (80 MHz, CD3COCD3): 0.82 s, 3 H
(Me-5β); 0.96 s, 6 H (Me-4α and Me-4β); 1.10 d, 3 H, J(Me,14) = 7.3 (Me-14β). 1H NMR (80 MHz,
C6D6): 0.75 s, 3 H (Me-4α); 0.77 s, 3 H (Me-4β); 0.81 d, 3 H, J(Me,14) = 7.3 (Me-14β); 0.88 s,
3 H (Me-5β). MS, m/z (%): 262 (M+, 89), 247 (5), 205 (9), 190 (9), 177 (100), 149 (45), 135 (15),
121 (18), 107 (16), 95 (21), 81 (24). For C18H30O (262.4) calculated: 82.4% C, 11.5% H;
foun d: 82.6% C, 11.7% H.
Com poun d 3 (122.4 m g, 0.266 m m ol) afforded 14-oxo-des-D-13α-androstan-3β-yl acetate
(9a; 14.9 m g, 19%), 14-oxo-des-D-androstan-3β-yl acetate (9b; 5.5 m g, 7%), 3β-hydroxy-des-D-
13α-androstan-14-one (9c; 14.9 m g, 22%) an d an un separated m ixture (11.1 m g, 18%). Com -
poun d 9a, m .p. 136–138 °C (colourless n eedles from ligh t petroleum ). TLC: RF 0.49 (ligh t
petroleum –eth er, 3 : 1). IR: 2 940, 2 868, 1 730, 1 700, 1 450, 1 365, 1 230, 1 130, 1 028,
885. 1H NMR (80 MHz): 0.89 s, 3 H (Me-10β); 1.00 d, 3 H, J(Me,13) = 6.2 (Me-13α); 2.02 s, 3 H
(CH3CO2); 4.68 m , 1 H (H-3α). 13C NMR (100 MHz): 11.72 (q), 14.47 (q), 21.39 (q), 24.95 (t),
25.62 (t), 27.25 (t), 27.39 (t), 33.72 (t), 35.36 (t), 36.32 (s), 36.70 (t), 43.53 (d), 44.96 (d),
49.46 (d), 55.35 (d), 73.25 (d), 170.59 (s), 214.29 (s). MS, m/z (%): 292 (M+, 12), 232 (100),
217 (15), 199 (11), 178 (78), 134 (63), 108 (61), 93 (50), 81 (44), 67 (41). For C18H28O3
(292.4) calculated: 73.9% C, 9.65% H; foun d: 73.7% C, 9.8% H. Com poun d 9b (colourless
oil). TLC: RF 0.39 (ligh t petroleum –eth er, 3 : 1). IR: 2 940, 2 868, 1 730, 1 700, 1 445, 1 360,
1 250, 1 125, 1 038, 895. 1H NMR (80 MHz): 0.90 s, 3 H (Me-10β); 1.17 d, 3 H, J(Me,13) =
7.3 (Me-13β); 2.02 s, 3 H (CH3CO2); 4.67 m , 1 H (H-3α). MS, m/z (%): 292 (M+, 9), 232
(100), 217 (15), 199 (15), 178 (96), 134 (74), 108 (72), 93 (72), 79 (61), 67 (41). For C18H28O3
(292.4) calculated: 73.4% C, 9.65% H; found: 74.1% C, 9.9% H. Com pound 9c, m .p. 116–117 °C
(colourless n eedles from eth an ol). TLC: RF 0.10 (ligh t petroleum –eth er, 5 : 1). IR: 3 430, 2 940,
2 860, 1 700, 1 435, 1 370, 1 245, 1 130, 1 070, 1 045. 1H NMR (80 MHz): 0.88 s, 3 H
(Me-10β); 0.99 d, 3 H, J(Me,13) = 6.2 (Me-13α); 3.60 m , 1 H (H-3α). 13C NMR (100 MHz):
11.93 (q), 14.49 (q), 25.02 (t), 25.70 (t), 27.37 (t), 31.35 (t), 35.46 (t), 36.35 (s), 36.96 (t),
37.68 (t), 43.71 (d), 44.99 (d), 49.56 (d), 55.55 (d), 70.96 (d), 214.52 (s). MS, m/z (%): 250
(M+, 89), 232 (55), 217 (13), 199 (12), 189 (11), 178 (38), 159 (15), 147 (23), 134 (23), 125 (36),
120 (47), 108 (100), 93 (57), 81 (51), 69 (49), 55 (62). For C16H26O2 (250.4) calculated: 76.7% C,
10.5% H; foun d: 76.5% C, 10.3% H.
Com poun d 4 (203.6 m g, 0.489 m m ol) afforded des-D-5α,13α-cholestane-3,14-dione (10a;
71.9 m g, 59%) an d (2E,4R)-4,8-dimethylnon-2-en-1-al (11; 30.5 m g, 55%). Com poun d 10a
(colourless oil). TLC: RF 0.37 (light petroleum –ether, 4 : 1). IR: 2 928, 2 864, 1 706, 1 442, 1 364,
1 220, 1 160, 1 122. 1H NMR (80 MHz): 1.01 d, 3 H, J(Me,13) = 6.2 (Me-13α); 1.08 s, 3 H
(Me-10β). MS, m/z (%): 248 (100), 230 (13), 215 (13), 190 (26), 124 (72), 108 (33), 95 (33),
81 (48), 67 (44), 55 (72). For C16H24O2 (248.4) calculated: 77.4% C, 9.7% H; foun d: 77.6% C,
9.8% H. Com poun d 11 (colourless oil). TLC: RF 0.60 (ligh t petroleum –eth er, 4 : 1). 1H NMR
(400 MHz): 0.84 d, 6 H, J(8,9) = J(Me,8) = 6.0 (3 × H-9 an d Me-8); 1.04 d, 3 H, J(Me,4) = 6.6
(Me-4); 6.05 ddd, 1 H, J(2,3; 1,2; 2,4) = 15.6, 7.7, 0.9 (H-2); 6.74 dd, 1 H, J(2,3) = 15.6, J(3,4) =
7.3 (H-3); 9.48 d, 1 H, J(1,2) = 7.7 (H-1).
Collect. Czech. Chem. Commun. (Vol. 64) (1999)

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Com poun d 6 (130.9 m g, 0.324 m m ol) afforded 12a (2.5 m g, 4%) an d 12b (on ly detected
on TLC).
Com poun d 7 (99.7m g, 0.231 m m ol) afforded des-A-10α-cholestan-5-one (12a; 2.9 m g, n et
yield 13%), des-A-cholestan-5-one (12b; 0.5 m g, 2%) an d recovered 7 (70.2 m g). Com poun d
12a, m .p. 60.5–62 °C (colourless n eedles from ligh t petroleum ) (ref.12a, 61–62 °C; ref.12b
,
62–63 °C). TLC: RF 0.32 (ligh t petroleum –eth er, 5 : 1). IR: 2 928, 2 856, 1 700, 1 450, 1 371,
1 158, 840. 1H NMR (80 MHz): 0.75 s, 3 H (3 × H-18); 0.87 d, 6 H, J = 6.0 (3 × H-26 and 3 × H-27);
0.93 d, 3 H, J = 6.2 (3 × H-21); 1.00 d, 3 H, J = 6.6 (Me-10α). MS, m/z (%): 332 (M+, 100),
317 (2), 304 (2), 275 (7), 360 (7), 247 (6), 217 (11), 201 (11), 192 (13), 177 (99), 163 (11),
150 (20), 136 (26), 121 (22), 110 (26), 95 (22), 81 (22), 69 (22), 55 (43). Com poun d 12b,
m .p. 79–81 °C (colourless n eedles from ligh t petroleum ). TLC: RF 0.25 (ligh t petroleum –eth er,
5 : 1). IR: 2 930, 2 865, 1 705, 1 465, 1 379, 1 170, 741. 1H NMR (400 MHz): 0.727 s, 3 H (3 × H-18);
0.864 d, 0.868 d, 2 × 3 H, J = 6.6 (3 × H-26 an d 3 × H-27); 0.918 d, 3 H, J = 6.5 (3 × H-21);
1.118 d, 3 H, J = 7.2 (Me-10β); 2.214 dt, 1 H, J(6α,6β) = 14.0, J(6α,7α) = J(6α,7β) = 4.9 (H-6α);
2.382 m , 1 H (H-10α); 2.515 td, 1 H, J(6α,6β) = 14.0, J(6β,7α) = J(6β,7β) = 6.5 (H-6β). MS,
m/z (%): 332 (M+, 65), 317 (4), 260 (7), 219 (7), 192 (15), 177 (100), 136 (26), 95 (30), 55
(54).
Con version of 8b, 9b or 12b to m ore Stable Epim ers 8a, 9a or 12a
A m ixture of 8b (or 9b, or 12b) (0.5 m g) in eth an ol (0.5 m l) an d acetic acid (1 drop) was
stirred at room tem perature for 1 h . TLC an alysis sh owed th at 8b (or 9b, or 12b) was tran s-
form ed to 8a (or 9a, or 12a).
RESULTS AND DISCUSSION
Modification of Albrecht’s et al. Apparatus
Th e Albrech t’s m eth od6 with (20R,S)-4,4,5,14-tetram eth yl-18,19-din or-
13,17-seco-5β,8α,9β,10α,14β-cholestane-13,17-dione (1) as a substrate proved
to be im practical as th e startin g m aterial was n ot efficien tly carried in to th e
catalysis tube in a reason able tim e. Th e work-up for th e extraction of th e
products was troublesom e because of th e large quan tity of th e water solu-
tion obtain ed. Th erefore, th e apparatus for th is reaction was m odified by
in troducin g an in let between th e preh eatin g tube an d th e catalysis tube
(Fig. 1). Th e 1,5-dicarbon yl com poun ds dissolved in eth er could be in jected
in to th e in let after th e steam goin g sm ooth ly.
Retro-Michael Reaction of 1,5-Dicarbonyl Compounds
Com poun d 1 was in troduced in to th e in let of th e reactor (see Sch em e 1) to
give a m ixture of tricyclic keton es 8a (57%) an d 8b (16%) in a com bin ed
isolated yield of 73%. Com poun ds 8a an d 8b could be separated by silica
gel colum n ch rom atograph y. Keton es 8a an d 8b were epim ers at C-14 an d
Collect. Czech. Chem. Commun. (Vol. 64) (1999)

Retro-Michael Reaction
111
1
th eir structure was ch aracterized by IR, H NMR an d 13C NMR spectra. Th eir
1H NMR spectra sh owed doublets at 1.058 (J = 6.5) an d at 0.81 (J = 7.3) ppm
assign ed to 14α-Me an d 14β-Me in 8a an d 8b, respectively. Th ese assign -
m en ts were con sisten t with th e sim ilar com poun ds6. Mass spectra of both
8a an d 8b sh owed a base peak at m/z 177 (M+ – rin g – C). Th e less stable
epim er 8b could be con verted to th e m ore stable epim er 8a un der acid con -
dition s. Th e α,β-un saturated keton e arisin g from side ch ain was n ot col-
lected due to its sm all yield an d volatility but it could be detected on TLC.
Th e retro-Mich ael reaction of 3 resulted in a com plex m ixture from wh ich
9a (19%), 9b (7%) an d 9c (22%) were isolated an d ch aracterized. Com -
poun ds 9a an d 9b were two epim ers of th e expected keton es an d 9c was a
1
h ydrolysis product of 9a as con firm ed by its IR, H NMR an d 13C NMR spec-
1
tra. Th e H NMR spectra of 9a an d 9c sh owed doublets at 1.00 (J = 6.2) an d
1
at 0.99 ppm (J = 6.2) assign ed to 13α-Me in 9a an d 9c, respectively. Th e H
NMR spectrum of epim er 9b displayed a doublet at 1.17 ppm (J = 7.3) as-
sign ed to 13β-Me. Th e above couplin g con stan ts were con sisten t with th ose
of 8a an d 8b, respectively. Both 9a an d 9b sh owed an acetoxy m eth yl at
2.02 ppm as sin glet. Th e less stable epim er 9b could be sm ooth ly con verted
to 9a un der acid con dition s. Th e m ass spectra of 9a an d 9b in dicated base
peak at m/z 232 (M+ – AcOH), whereas that of 9c showed m/z 232 (M+ – H2O).
It is worth n otin g th at th e less polar product (18%) of th e retro-Mich ael re-
action of 3 was still a com plex m ixture of, presum ably, th e h ydroly-
sis-deh ydration or deh ydration products of 9a an d 9b or 9c with double
bon d isom ers in rin g A an d epim ers at C-13.
After substitution of 3β-acetoxy group with a carbon yl, keton e 4 worked
well un der retro-Mich ael reaction con dition s an d clean ly gave tricyclic di-
keton e 10a with an isolated yield of 59%. Th e less stable epim er was n ot
thermometer
inlet
catalysis tube
condenser
preheating tube
steam
electric heating
FIG. 1
Th e apparatus for retro-Mich ael reaction
Collect. Czech. Chem. Commun. (Vol. 64) (1999)

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Wang, Li:
1
isolated. The H NMR spectrum of 10a showed doublet at 1.01 ppm (J = 6.2) as-
sign ed to th e 14α-Me. Th e m ass spectrum of 10a in dicated a base peak at
m/z 248 (M+). Th ese results dem on strated th at th e retro-Mich ael reaction of 4
worked better th an th at of substrate 3. Th e oth er product (2E,4R)-4,8-
dim eth yln on -2-en -1-al (11) from com poun ds 3 an d 4 was collected an d
1
1
ch aracterized by H NMR spectrum . Th e H NMR of 11 sh owed a doublet at
9.48 ppm (J = 7.7) assigned to the aldehyde proton. The signals at 6.05 ddd
ppm (J = 15.6, 7.7 an d 0.9) an d 6.74 dd ppm (J = 15.6 an d 7.3) were as-
sign ed to H-2 an d H-3, respectively. Th e Me-4 reson ated at 1.04 d ppm (J =
6.6) wh ereas Me-8 an d H-9 at 0.84 d ppm (J = 6.0). Th is com poun d was ob-
tain ed by Corn forth et al. on th eir studies of th e structure of ch olesterol13.
Th e retro-Mich ael reaction of acid 6 gave a low con version rate (<30%)
an d a very poor yield (4%) of 12a an d 12b, wh ereas for th e eth yl ester 7, a
little better yield of 12a an d 12b (com bin ed 15%) was obtain ed. Meltin g
O
O
H
H
H
H
(i)
Me
H
H
O
8a, 14α-Me
8b, 14β-Me
1
(ii)
Me
O
H
H
H
(i)
+
CHO
2
H
H
O
1
2
H
R
R
H
1
2
R
R
CHO
11
H
H
1
1
2
3, R = H; R = OAc
9a, R = H; R = OAc; 13α-Me
1
2
(ii)
1
2
4, R + R = O
9b, R = H; R = OAc; 13β-Me
1
2
9c, R = H; R = OH; 13α-Me
OR
H
(iii)
H
Me
O
H
H
H
H
12a, 10α-Me
12b, 10β-Me
6, R = H
7, R = Et
(ii)
O
O
+
o
o
(i) NaOH, H O (g), 250 C; (ii) H ; (iii) KOH, H O (g), 250
C
2
2
SCHEME 1
Collect. Czech. Chem. Commun. (Vol. 64) (1999)

Retro-Michael Reaction
113
poin t of 12a was con sisten t with th e literature12. Th e 1H NMR spectra of
12a an d 12b sh owed doublets at 1.00 ppm (J = 6.6) an d 1.118 ppm (J = 7.2)
wh ich were assign ed to th e 10α- an d 10β-Me in 12a an d 12b, respectively.
Th e couplin g con stan ts were con sisten t with th ose of th e above obtain ed
com poun ds (8a an d 8b, 9a an d 9b, an d 10a). Th e m ass spectra of 12a an d
12b sh owed th eir m olecular ion s in h igh abun dan ce. For 12a th e base peak
was m/z 332 (M+) an d m/z 177 (M+ – rin g – C) was in a relative abun dan ce
of 99%, wh ile for 12b m/z 177 (M+ – rin g – C) was a base peak with th e m o-
lecular ion s (m/z 332) in 65% in ten sity. Th e con version of 12b to 12a could
be also ach ieved un der acid con dition s. Th e low con version rate of 6 an d 7
an d poor cleavage yield were probably due to th eir lower volatility an d less
active α-H to carboxyl or ester group in 6 an d 7.
From th e above results, we can con clude th at th e retro-Mich ael reaction
of 1,5-dicarbon yl com poun ds works well for 1,5-diketon es an d 1,5-keto al-
deh ydes, h owever, for 1,5-keto esters an d 1,5-keto acids gives on ly poor
yields.
The project was supported by NSFC (29572039), Natural Science Foundation of Hebei Province
(297065) and Science and Technology Commission of Hebei Province.
REFERENCES
1. Wang T. G., Sheng G. Y., Chen J. H., Fu J. M.: Sci. China, Ser. D 1996, 39, 74.
2. Allen C. F. H., Happ G. P.: Can. J. Chem. 1964, 42, 655.
3. Arigoni D., Viterbo R., Dunnenberger M., Jeger O., Ruzicka L.: Helv. Chim. Acta 1954, 37,
2306.
4. Barton D. H. R., Mayo de P., Orr J. C.: J. Chem. Soc. 1958, 2239.
5. Baddeley G. V., Halsall T. G., Jones E. R. H.: J. Chem. Soc. 1964, 1173.
6. Aqunio Neto F. R., Trendel J. M., Albrecht P.: Tetrahedron 1986, 42, 5621.
7. a) Aqunio Neto F. R., Restle A., Connan J., Albrecht P., Ourisson G.: Tetrahedron Lett.
1982, 23, 2027; b) Trendel J. M., Restle A., Connan J., Albrecht P.: J. Chem. Soc., Chem.
Commun. 1982, 304.
8. a) Li T. S., Yang Y. T., Li Y. L.: J. Chem. Res., Synop. 1993, 28; b) Yang J., Li T. S., Li Y. L.:
Chin. Chem. Lett. 1996, 7, 997.
9. Li T. S., Li Y. L., Liang X. T.: Steroids 1990, 55, 263; and references therein.
10. Turner R. B.: J. Am. Chem. Soc. 1950, 72, 579.
11. Johnstone R. A. W., Rose M. E.: Tetrahedron 1979, 35, 2169.
12. a) Edward J. T., Lawson N. E.: J. Org. Chem. 1970, 35, 1426; b) Hartshorn M. P., Jones E. R. H.:
J. Chem. Soc. 1962, 1312.
13. Cornforth J. W., Youhotsky I., Popjak G.: Nature 1954, 173, 536.
Collect. Czech. Chem. Commun. (Vol. 64) (1999)