close

Вход

Забыли?

вход по аккаунту

?

Hetero Diels-Alder Reactions for the Synthesis of Thromboxane Intermediates.

код для вставкиСкачать
Table I. 'H- and "C-NMR chemical shifts and H,H coupling constants (in
Hz) of 1 and 2.
l(6)
2(5,7,10)
3(4,8,9)
CH?
II
1 la1
2 [b]
-
1 [c]
2 [d]
44.4
41.9
5.41
4.49
140.8
95.2 [el
5.45
4.29
122.3
88.8 [el
1.25
0.49
31.6
41.9
2.53
-0.77
50.8
49.0
JZ.1
0.58
1.21
Jli
534
0.97
0.16
7.19
7.93
Position
'~
'I'
JZ3
1
2
11.60
8.61
OH
On
1
TXB,
a:
._ RO
c(>
r
RO
R
2
[a] CDCI,, 400 MHz, 35°C [19]. [b] [D,]THF, 90 MHz, -20°C. [c] CDCI,, 20
MHz, 35°C. [dl [D,]THF, 22 MHz, -20°C. [el Assignment not confirmed.
A comparison of the I3C-NMR spectra of 1 and 2 reveals the upfield shift of the signals of 2 characteristic for
a dianion.
If the formation of 2 is accompanied by pronounced
conjugative stabilization, then transfer of the second electron (conversion of the radical anion into the dianion)
should be facilitated. The transfer of two electrons, and an
ECE mechanism, could be demonstrated cyclovoltammetrically (THF, 0.2 M NaBPh,, Ag as quasi-reference electrode). In a reversible E-step (EYg -2.1 V) a radical anion is
formed which is then converted in a rapid irreversible Cstep into a conjugatively stabilized TI system. This conversion favors formation of the dianion, and the redox potential of the second electron transfer shifts anodically
(E! = - 1.8 V; i. e. > Ey). Conversely, in the case of reduction of two neighboring butadiene moieties, E! would
be shifted cathodically compared with G.
There are convincing arguments against a bishomoconjugation in the neutral and anionic n system considered
earlier['-31.Our findings clearly show that, for steric and
electronic reasons-equal "through space" coupled n fragments are present- 2 is a bishomoconjugatively-stabilized
species with ten TI electrons.
+
H
OAR2
3
4
Scheme 1.
Exploitation of the hetero Diels-Alder reaction for the
synthesis of the target molecule 2, which has a pseudoglycal structure, requires: (i) a I-alkoxy-1,3-diene 3 bearing a
substituent R ' which contains two C-atoms and enables
stereospecific incorporation of the OH group at C-3 in 2
as well as coupling of the side chain, and (ii) a carbonyl
compound 4, whose substituent R2 increases the dienophilicity and allows construction of the second side
chain.
/OAC
OM e
Me
COOEt
7
10
9
8
..m
of
Received: December 28, 1981 [Z 40 IE]
German version: Angew. Chem. 94 (1982) 294
The complete manuscript of this communication appears in:
Angew. Chem. Suppl. 1982. 566-574
[ I ] L. A. Paquette, Angew. Chem. 90 (1978) 114: Angew. Chem. Inf. Ed.
Engl. 17 (1978) 106, and references cited therein.
121 J. B. Grutzner, W. L. Jsrgensen, J . Am. Chem. SOC.103 (1981) 1372.
131 E. Kaufmann, H. Mayr, J. Chandrasekhar, P. von R. Schleyer, J . Am.
Chem. SOC.103 (1981) 1375.
[4] J. Frank, W. Grimme, J. Lex, Angew. Chem. 90 (1978) 1002: Angew.
Chem. I n f . Ed. Engl. 17 (1978) 943.
[I91 We thank Prof. Dr. H. Giinther, Siegen, for recording the 400-MHz 'HNMR spectrum.
1
-
4
- dOO
COOH
+-+
e, f
MeO"'aC00R
~ e @ '
llA
12
oc,,
8°TBDMs
o-fTBDMS
$'
+
MeO""
COOH
13
TXB,
MeO"
14
6, 8-12, R = (-)-Menthy1
Hetero Diels-Alder Reactions for the Synthesis of
Thromboxane Intermediates**
By Richard R. Schmidt* and Wolfgang Abele
Reactive pseudoglycals, which are useful intermediates
for the synthesis of modified carbohydrates, have been
synthesized by hetero Diels-Alder reactions"]. This type of
reaction should also be useful for the synthesis of the carbohydrate-derived thromboxanes such as TXBz (Scheme
Cycloaddition of the (Z,E)-l-methoxy-l,3-hexadiene
1).
[*] Prof. Dr. R. R. Schmidt, Dr. W. Abele
[**I
Scheme 2. Only the D-isomers are shown. TBDMS=ferf-butyl(dimethyl)silyl.
a : C,,H,,, 120°C, 72 h: yield 62% (8: 3l%, 9: 26%, 10: 5%) or CH2C12,60"C,
96 h, 8.5 kbar; yield 71% (8: 35%, 9: 30%. 10: 6%). b: Et20, BF3.0Etl, RT:
yield 100% 10, colorless oil. c: MeOH, Na2COI, RT, I2 h; yield 75%. d : Dimethylformamide (DMF), pyridinium dichromate, RT, 8.5 h: yield 57% 12,
m.p. 166-168OC (n-hexane). e: Tetrahydrofuran (THF), KIAZ, RT, 5 h;
yield 94O/0. f : Toluene, n-Bu,SnH, 80°C. 30 h; yield 92% 11, colorless oil. g:
Toluene, DIBAH, -7O"C, 20 h: yield 70%. h: DMF, TBDMS-CI, 40°C. 1.5
h; yield 92%. i: NaOH, EtOH, 40"C, 24 h: yield 77% 13, colorless oil. j : Toluene, DIBAH, -70°C. 12 h; yield 54% 14, colorless oil.
Fakultat fur Chemie der Universitat
Postfach 55 60, D-7750 Konstanz 1 (Germany)
De novo Synthesis of Carbohydrates and Related Natural Products,
Part 8. This work was supported by the Deutsche Forschungsgemeinschaft and the Fonds der Chemischen 1ndustrie.-Par! 7: [Ic].
302
0 Verlag Chemie GmbH. 6940 Weinheim. 1982
5[51,which bears a functionalized C2 substituent at C-4,
with menthyl (-)-glyoxylate 6 affords a mixture of the
pseudoglycaluronates 8 , 9 , and 10 that can be easily separated. A l : l mixture of 8 and 9 can also be obtained in
good yield from the mesoxalate adduct 7[']. 9 is catalytically converted with boron trifluoride-ether into the a-
0570-0833/82/0404-0302 $ 02.50/0
Angew. Chem. Int. Ed. Engl. 21 (1982) No. 4
anomer 10 in quantitative yield. The higher thermodynamic stability of 10 is due to the anomeric and allylic effects['], which are effective in the OH5 conformation of
lo[''. The compounds 9 and 10 have the necessary relative
stereochemistry at C-4 and C-5. After conversion['] into the
lactone 1 1 , reduction with equimolar amounts of diisobutylaluminum hydride (DIBAH) at -70°C affords the lactol. After reaction with terf-butyl(dimethyl)silyl chloride
(TBDMS-CI), the carboxylic acid 13 is obtained by ester
hydrolysis, and the aldehyde 14-an analogue of 1 -by
repeated reduction with DIBAH. The compounds 11, 13
and, in particular, 14 are valuable intermediates for
thromboxane syntheses.
Received: July 20, 1981 [Z 41 IE]
German version: Angew. Chem. 94 (1982) 298
The full manuscript of this communication appears in:
Angew. Chem. Suppl. 1982. 616-621
111 a) R. R. Schmidt, R. Angerbauer, Angew.
Chem. 89 (1977) 822: Angew.
Chem. I n t . Ed. Engl. 16 (1977) 783; b) R. R. Schmidt, R. Angerbauer,
Carbohydr. Res. 72 (1979) 272; ibid. 89 (1981) 159, 193: c) R. R. Schmidt,
A. Wagner, Synrhesis 1981. 272.
[ S ] W. Abele, R. R. Schmidt, unpublished results; W. Abele, Diplomarbeit
and Dissertation, Universitat Konstanz 1978 and 198 I , respectively.
[6] See [Ib] and references cited therein.
[7] "H, conformation was also observed in the pseudoglycaluronates 8 and
Table 2. Product distribution [%] in the reaction of O('P) with acyclic hydrocarbons.
Substrate
)-(
3^
'-f-'
&
Tertiary
alcohols
[a1
Secondary and
primary alcohols
+ketones
Epoxides
Ketones
(by C-C
cleavage) [b]
-
64 (97)
2
34
55 (73)
52 (75)
21
13
20
24
45 (82)
15
40
-
(57)
51 (67)
32
17
-
(771
(65)
4 (42)
12 (50)
[a] In parenthesis: relative yields after reduction of reaction mixture with lithium aluminium hydride. [b] In parenthesis: relative yield of C-C cleavage
products formed in the ozone ouidation.
This may be exemplified by the oxidation of 2,3-dimethylbutane, which results in 2,3-dimethyl-2-butanol (64%)
and 1,2-epoxy-2,3-dimethylbutane(340/0), and after reduction with lithium aluminium hydride in 97% of the tertiary
alcohol (Scheme 1). Reaction of 2,3-dimethylbutane and
O3 gave only 35% of the tertiary alcohol in addition to acetone (37%) and 3-methyl-2-butanone (28%)16].
12.
LiAlH4
181 A corresponding reaction sequence has been described: E. J. Corey, M.
Shibasaki, J. Knolle, Tetrahedron Lett. 1977, 1625: 0. Hernandez, ibid.
1978. 219.
I
Scheme 1.
Hydroxylation of Acyclic Alkanes
by Oxygen Atoms O(3P)--Comparison of
Ozone and O(3P) Oxidations of Alkanes**
By Elazar Zadok and Yehuda Mazur*
Ozone oxidation of saturated compounds leads to introduction of O H groups at tertiary positions131.This method
is generally applicable to saturated cyclic hydrocarbons,
but not to acyclic hydrocarbons which give comparatively
large amounts of ketones derived from cleavage of C-C
bonds''].
Looking for an alternative method, we utilized ground
state oxygen atoms (O(3P) atoms) generated by low-pressure microwave discharge of a C 0 2 / H e mixture in a flow
system121.We have recently found that 0 atoms produced
in this way convert saturated cyclohexane derivatives
mainly into tertiary alcohols and epoxides['I.
We have now applied this oxidation method to five
acyclic hydrocarbons and have found that also in these
cases the major products were tertiary alcohols and tertiary
epoxides (Table 2). Since reduction of these epoxides with
LiAIH, leads to the same tertiary alcohols, the reduction of
the total mixture of products gave the alcohols in comparatively high yields. The amounts of ketones derived from
C-C
bond cleavage is considerably lower than in the
ozone oxidation (Table 2).
[*] Prof. Dr. Y. Mazur, E. Zadok
Department of Organic Chemistry, The Weizmann Institute of Science
Rehovot (Israel)
[**I This work was supported by the USA-Israel Binational Science Foundation. Jerusalem.
Angew. Chem. Int. Ed. Engl. 21 (1982) No. 4
Although both ozone and O(3P) hydroxylate saturated
hydrocarbons, they operate by different mechanisms.
Ozonation of hydrocarbons involves electrophilic attack of
O3on C-H bonds, leading to reversible formation of a dipolar intermediate from which alcohols (C-H cleavage)
or ketones (C-C cleavage) are formed. Steric effects play
an important role in the ozone oxidation and are responsible in acyclic hydrocarbons for the fact that not only
C-H- but also C-C-bonds can readily be attacked.
The mechanism for the reaction of O(3P) with hydrocarbons probably involves H atom abstraction to form a radical pair"]. Radical combination in a solvent cage leads to
alcohols, while disproportionation of the radicals gives
olefins which are then epoxidized by 0 atoms. This reaction, which occurs when the 0-atom is colinear with the
C-H
bond, has comparatively small steric demandsl'"l
and does not differentiate between cyclic and acyclic hydrocarbons.
Received: August 6, 1981 [Z 45 I€]
German version: Angew. Chem. 92 (1982) 31 I
The complete manuscript of this communication appears in:
Angew. Chem. Suppl. 1982, 606-615
[ I ] E. Zadok, Y. Mazur, J. Org. Chem.. in press.
[2] E. Zadok, D. Amar, Y. Mazur, J. Am. Chem. Soc. 102 (1980) 6369.
[31 Z. Cohen. E. Keinan, Y. Mazur, T. H. Varkony, J. Org. Chem. 40 (1975)
2141.
161 D. Tal, E. Keinan, Y. Mazur, J . Am. Chem. SOC.I01 (1979) 502.
[lo] P. Andersen, A. C. Lunz, J. Chem. Phys. 72 (1980) 5842,5851.
0 Verlag Chemie GmbH, 6940 Weinheim. 1982
0570-0833/82/0404-0303 $ 0 2 . 5 0 / 0
303
Документ
Категория
Без категории
Просмотров
1
Размер файла
213 Кб
Теги
synthesis, reaction, intermediate, alder, thromboxane, hetero, diels
1/--страниц
Пожаловаться на содержимое документа