Syntheses of Natural Products

120 Pages·1980·2.036 MB·English

by  Stuart G. Warren (auth.)

1
Topics in Current Chemistry
Fortschritte der Chemischen Forschung
Syntheses of Natural Products
Springer-Verlag
Berlin Heidelberg New York 1980
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ISBN 3-540-09827-5 Springer-Veflag Berlin Heidelberg New York
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Library of Congress Cataloging in Publication Data. Main entry under title: Syntheses of natural products.
(Topics in current chemistry ; v. 91 ) Bibliography: p. Includes index. Contents: Warren, S. G. Reagents
for natural product based on the PhzPO and PhS groups. - Tsuji, J. Application to natural products syntheses.
Schuda, P. F. Aflatoxin chemistry and syntheses. 1. Natural products - Addresses, essays, lectures.
- 2. Chemistry, Organic- Synthesis- Addresses, essays, lectures. I. Warren, Stuart G. Reagents for natural
product based on the Ph2PO and PhS groups. 1980. II. Tsuji, Jiro, 1927 - Application to natural product
syntheses. 1980. III. Schuda, Paul F., 1952 - Aflatoxin chemistry and syntheses, 1980. IV. Series. QD1 .F58.
vol. 91. [QD415.2]. 540s. [547.7'0459] 80-12663
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Contents
Reagents for Natural Product Synthesis Based on the PhzPO and PhS Groups
S. Warren
Applications of Palladium-Catalyzed or Promoted
Reactions to Natural Product Syntheses
J. Tsuji 29
Aflatoxin Chemistry and Syntheses
P. F. Schuda 75
Author Index Volumes 50 - 91 113
Editorial Board:
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Reagents for Natural Product Synthesis
Based on the PhzPO and PhS Groups
Stuart G. Warren
ytisrevinU Laboratory, Road, Cambridge Chemical Lensfietd 2BC ,WE1 England
Table of Contents
1 Introduction . . . . . . . . . . . . . . . . . . . . 2
2 Regiospecific Allyl Synthons . . . . . . . . . . . . . . . 4
Z 1 Regiospecific Reagents for Allyl Anions . . . . . . . . . . . 4
2.2 The Allyl to Vinyl Transposition: Synthesis of Allyl Alcohols from a
Vinyl Anion Equivalent . . . . . . . . . . . . . . . . . 6
2.3 Regiospecific Allyl Cation Reagents . . . . . . . . . . . . . 7
2.4 Epoxides ofAUyl Phosphine Oxides as Allyl Cation Equivalents 9
3 Acyl Anion Equivalents for 1,2-Alkylative Carbonyl Transpositions . 10
3.1 Synthesis of Aldehydes 63-*64, R=H . . . . . . . . . . . . 10
3.2 Synthesis of Ketones . . . . . . . . . . . . . . . . . 12
3.2.1 From Sutphenylated Phosphine Oxides . . . . . . . . . . . 12
3.2.2 From Bis-(Phenylthio-)Acetals . . . . . . . . . . . . . . 13
4 Specific Enol Equivalents . . . . . . . . . . . . . . . . 14
4.1 a-(Phenylthio-)Ketones . . . . . . . . . . . . . . . . 14
4.2 Synthesis of Butenolides . . . . . . . . . . . . . . . . 16
5 Reagents for the Synthesis of 1,4-Dicarbonyl Compounds and Enones . 17
6 Homoenolate Equivalents . . . . . . . . . . . . . . . . 18
7 Reagents for the Synthon -C=C-CO . . . . . . . . . . . . 21
8 Phenylthio Butadienes for Diels-Alder Reaction . . . . . . . . . 23
9 References . . . . . . . . . . . . . . . . . . . . . 25
s. Warren G.
1 Introduction
The disconnection approach to the design of organic syntheses was devised by
Corey t) largely for use by computers .)2 It is equally suitable for use by people3);
even Corey has discarded his IBM on occasions .)4 In some respects this fundamental
approach contrasts with the "key reaction" approach used, for example, by
Oppolzer s) in his recent synthesis of Longifolene .)a However, both approaches have
focussed attention on synthons b) - idealised fragments into which the target mole-
cule may be broken, and on the need for reagents - corresponding to these synthons
which are regiospecific in the sense that they have nucleophilic or electrophilic
reactivity at one specific carbon atom .)9
a
0 0
1 2 3
-O
4
Conventional disconnection of the enone 1 at a suggests an unlikely aldol con-
densation between the aldehyde 2 and the unsymmetrica ketone 3; unlikely because
one specific enolate 4 out of a possible three must react with only one of the two
carbonyl groups. Successful solutions to this problem may use specific enol equiv-
alents 0) I for 4 such as enamines )11 or enol silanes 12); both have been used in the
synthesis of many natural products. Alternatively, we may choose a different dis-
connection, say b in 5, and use an epoxide and the acyl anion 6, a synthon with in-
verted polarity or umpolung 9' 13) Reagents for 6 include those based on sulphur ,)41
particularly dithians is), and this strategy has been used for the synthesis of a few
natural products, mostly enals .)61
b b
1 .... x R I ~ R 2 > RII-.~O + -~-..R2
HO O O
5 6
Specific enol equivalents (e. g./3-keto esters) and umpolung (e. g., with cyanide
or acetytide ions as acyl anion equivalents) have of course been used in synthesis for
many years. What is new is the recognition of their role, as a result of the disconnec-
)a A compound previously regarded as the province of the disconnection approach )6
b) Synthon originally was used by Corey 7) to mean a part structure within the target molecule
recognisable sa the product of a known reaction. He now suggests retron for 8). this meaning
Synthon si often loosely used to mean reagent a but the most 3, helpful usage )9 si synthon for
the fragment idealised .e( .g R- and tnegaer for its equivalent .e( .g RLi) ni the ,ksalf
stnegaeR rof larutaN tcudorP sisehtnyS
tion approach, and it is this that has led to the many recent developments. The same
is true of functional group transpositions '71 18). Alkylative carbonyl transposi-
tions is) have proved particularly useful in the synthesis of natural products whose
complicated structures are often much easier to analyse after disconnecting a C-C
bond and relocating a carbonyl group at a more convenient site in a single operation.
Examples of two types of 1,2-alkylative carbonyl transpositions occur in Corey's
occidentalol synthesis ,)91 and in Oppolzer's acorenone synthesis 2°). In the first,
748, the carbonyl group is moved forwards into the newly added part of the mole-
cule. In the second, 9 ~ 10, the carbonyl group is moved backwards around the
original framework.
7 8
9
HOsT
0
H~-s~ 10
R
R
11 12 13
1 R
~2hP RP~H
=R
14 15
eW have found )~2 that two functional groups, phenylthio (PhS) and diphenyl-
phosphinoyl (Ph2PO) will take part in a slightly differenotp eration - migration -
and form the allyl derivatives 12 and 15 in the acid catalysedr earrangement of
alcohols 11 and 14. The allyl sulphide 12 also rearranged photochemically by a [1,3]
PhS shift )22 to the new aUyl sulphide 13. Since both Ph2PO and to a lesser extent
S. G. Warren
PhS stabilise carbanions, these aUyl compounds 12, 13, and 15 form anions which
can be used in synthesis. This article describes further developments in our work with
these two groups, involving both migration and transposition, leading to regiospecific
reagents for synthons with normal reactivity or umpolung and their application to
natural product synthesis.
2 Regiospecific Allyl Synthons
Allyt anions and cations, e. .g 18, are useful in synthesis )32 in that they are stable
because they are delocalised and hence are easily made. But, for this very reason,
simple reagents such as allyl Grignards or allyl halides are rarely regiospecific or, if
they are, only one of the two isomers, e. g. 20 and not 19, can be made. In addition,
the reagents may interconvert by aUylic rearrangement '22 e. 24), g. 19 ,~ 20. So many
natural products contain allyl groups, particularly aUylic alcohols, that the need for
regiospecific reagents for allyl anions and cations is very great.
61 ~ 91
71 02
2.1 Regiospecific Reagents for Allyl Anions
Though some progress has been made in understanding the regiochemistry of allyl
anions17, 2s), their behaviour towards nucleophiles remains capricious. The anions of
allyt diphenylphosphine oxides are one of the most straightforward in their reactions
with carbonyl compounds. The allyl phosphine oxide 23, made by direct dehydra-
tion of 22 or by Ph2PO migration from 21, gives )62 an anion with butyl-lithium
(BuLi) which reacts exclusively ~t to phosphorus with aldehydes to give the alcohols
24. Each diastereoisomer of 24 (they are easily separted by chromatography) gives a
single geometrical isomer of the diene 25.
A degree of control over the geometry of the other double bond is also
)72
possible . Dehydration of either alcohol 26 or 27 gives mostly the E.allyl phos-
phine oxide 28 and this configuration is retained throughout anion formation,
addition to give 29, separation into diastereoisomers, and elimination to give a single
geometrical isomer of 30. One double bond in the diene 30 must have the E con-
figuration, but the configuration of the other is determined by which isomer of 29
is used.
stnegaeR rof larutaN tcudorP sisehtnyS
O
Ph2P~,~
1 lLuB.
t
l. iLuB .2 ~O
.2 OHCeM
Ph~~
./ HO"
HOsT H2OC3FC
22
12
Ph2i--~
| iLuB. /
23
.2 MeCHO/
HaN
Pha~~
/ HO"
52-E
24
2hP HOsT
H ,J_.(- 0 ~ ~R
R 2
26
R 2
o \o R, ~OC3FC / 28
I iLuB.l
.2 OHC3R
72
R~-~ liaN ~ hP
3 R 3 R
30 29
The allyl phosphine oxide approach to diene and polyene synthesis has been
used by Lythgoe )82 in his vitamin 3 D synthesis, and by Pattenden )92 in syntheses of
compounds such as 31.
.S .G nerraW
1 iLuB.
OHC t.
~ t i hp 2
13
The main classes of allyl phosphine oxide which cannot be used in diene syn-
theses, as they react in the 3°), are 0,-position those with an aryl group in the a-posi-
tion 32, or with a four 33 or five 34 membered ring. Those wijtuhs t one a-sub-
stituent and no/~- or 7-substituents 35 also give some 3,-adduct .)13
l R ~ R _~
o
rA R
32 33
Ph,
34 35
2.2 The AUyl to Vinyl Transposition:
Synthesis of Allyl Alcohols from a Vinyl Anion Equivalent
The carbonyl adducts of allyl phosphine oxides, e. g., 24 and 29 can also be used to
make allyl alcohols )23 by the reductive removal of the Ph2PO group with lithium
aluminium hydride: a reaction involving transposition of the double bond, e. g., 24 -*
36. In this approach, the allyl anion of 23 is a reagent for the vinyl anion synthon 37.
/ HO"
24 36 37
~4HIAiL
[P[:hP .2 --OHCeM Ph2P-~_OH
38