New Concepts I

149 Pages·1973·1.866 MB·English

by  Prof. Barry M. Trost (auth.)

Contents
Sulfuranes in Organic Reactions and Synthesis
B. M. Trost ..................................... ..........
Electron Correlation and Electron Pair Theories
W. Kutzelnigg ............................................. 31
Orbital Symmetry Rules for Inorganic Reactions from Perturbation
Theory
R. G. Pearson .............................................. 75
The Discovery of Organic Synthetic Routes by Computer
H. Gelernter, N. S. Sridharan, A. J. Hart, S. C. Yen, F. W. Fowler
and H.-J. Shue ............................................ 113
Suliuranes in Organic Reactions and Synthesis
Prof. Barry M. Trost
Department of Chemistry, University of Wisconsin, Madison, Wisconsin, USA
Contents
I. Introduction ...................................................... 2
II. r~ Sulfurane Addition Reactions ..................................... 3
A. Spiroannelation ................................................ 4
3. v-Butyrolactone Synthesis ....................................... 7
C. Geminal Alkylation ............................................. 7
D. Secoalkylation ................................................. 8
III. ~-Elimination Reactions of ~ Sulfuranes .............................. 10
IV. a Sulfuranes ...................................................... 12
A. Arylsulfuranes ................................................. 12
B. Alicyclic Sulfuranes ............................................ 21
1. Three-Membered Rings ....................................... 2!
2. Four-Membered Rings ........................................ 22
3. Five-Membered Rings ........................................ 23
V. Thiophene Synthesis ............................................... 26
VI. Conclusions ....................................................... 26
Acknowledgment .................... .............................. 27
VII. References ....................................................... 27
B. M. Trost
I. Introduction
Sul/uranes are a class of compounds in which sul/ur expanded its [ormal
valence shell [rom eight to ten electrons. There are two types of sul[uranes to eb
considered -- ~ sul[uranes and a sul/uranes. A ~ sul[urane possesses three
sigma bonds and one pi bond. Only to the extent that back orbital overlap
/c-s\ ,/-\. \c-s/.
cr sulfurane
•
between a filled p orbital on carbon and the empty d orbitals on sulfur is
important has sulfur experienced valence shell expansion. These species
are more commonly known as ylides. A sigma sul[urane possesses [our
sigma bonds to sul]ur in addition to the lone pair. Such a valence shell
'., I
"2F: ~ sulfurane
expansion creates a strong driving force for reaction by allowing sulfur
to return to the more stable octet state by loss of two electrons. For the
sulfuranes, such a reaction may be achieved with minimum loss of bonding
energy by cleavage of the weak r7 bond generating a carbene and a dialkyl-
sulfide (Eq. 1). Alternatively, the a sulfuranes may return to the octet state
\c-s/. , ~/c: :<:
/ -- \. + )1(
by either cleavage of one substituent with both bonding electrons to gener-
ate a carbanion and a sulfonium salt (Eq. 2) or of two substituents with
concomitant bonding to generate a new carbon-carbon bond and a dialkyl-
sulfide (Eq. 3).
c ~s : +e: )2(
%1 ---.
";S--
I c~ : - - /c
c c-c+ :S\c )3(
The two types of sulfuranes are related by consideration of their origin.
Treatment of sulfonium salts with strong bases (normally organolithium)
serves as the major technique of generating ~ sulfuranes. Nevertheless, it
2
Sulfuranes in Organic Reactions and Synthesis
must be considered that sulfonium salts are potentially ambident in their
behavior towards nucleophiles such as the organolithium bases. Instead of
deprotonation, addition to the electrophilic sulfur may occur with formation
of the sigma sulfurane. Indeed, many by-products observed in = sulfurane
H.. e/ " ;fc--s H ¸
fC--S, x and R~"
reactions can now be attributable to the decomposition of. sulfuranes. In
some instances, . sulfurane generation may compete so favorably that it
becomes the predominant or exclusive mode of reaction. Both types of
sulfuranes have applications in organic synthesis.
II. ~ Sulfurane Addition Reactions
The = sulfuranes are isoelectronic with diazo Compounds and therefore
may be expected to possess very similar chemical reactivity. 1-3) However,
the zwitterionic character of these intermediates is greater than that of
diazo compounds thereby facilitating their nucleophilic additions to car-
bonyl groups and Michael acceptors such as ~,~-unsaturated carbonyl
systems. Diphenylsulfoniumallylide serves as a typical example.4) Thus,
it reacts with 4-t-butylcyclohexanone to give the epoxide with predomi-
nantly the trans configuration and with methyl acrylate to yield the cyclo-
propane after 1,3-elimination. Many new types and new reactions of
'J ,f,,co2cH3
Ph 2 S=CHCH=CH2 .,
.I~"C05 aHC
sulfuranes (sulfur ylides) remain to be discovered. Diphenylsulfoniumcyclo-
propylide is one such example. )5 The precursor sulfonium salt is readily
available in large quantities by the route outlined below. The ylide is avail-
.3 .M Trost
able from the salt irreversibly by treatment with dimsylsodium at --30
to -- 40 °C or preferably reversibly by treatment with powdered potassium
hydroxide.
O
2hP S 2hP Sx.~x.~l 4FB O Nail 4FB e
I ~ C I AgBF4 ~ THF
aHC ON 2
@ O
HOK ~ 2HCaN _,maHCS
BF #
A. Spiroannelation
Reactions of diphenylsulfoniumcyclopropylide with aldehydes and ketones
produces the very reactive oxaspiropentanes in high yield.5, )6 As the ex-
amples in Table t illustrate, electronically and stericalty unreactive carbonyl
groups produce the desired products well. The fascinating chemistry of
these reactive compounds remains to be explored on the whole. However,
they undergo facile rearrangement to cyclobutanones in quantitative
yields upon acid treatment. Since rearrangement can be achieved upon
Table .1 Spiroannelations
Carbonyl Oxaspiropentane Cyclobutanone o/° Yield
O
86
O
49
O
79
4
Sulfuranes in Organic Reactions and Synthesis
Table 1 (continued)
Carbonyl Oxaspiropentane Cyclobutanone % Yield
o.c~ j ~ 78
o
0
o
~0 ~ ~ 0 9 5
..
o ~ o ~
3 5
~o ~
80
0 0 a) 0,%_.~.,
75
PhCPh Ph Ph
Ph Ph
a) Not isolated but directly rearranged to cyclobutanone.
)b The yields have not been optimized in most cases.
5
B. .M Trost
o
working-up the initial reaction mixture, this procedure serves as an extreme-
ly general and versatile one-step cyclobutanone synthesis. The acid catalyzed
epoxide rearrangement proceeds via carbonium ion intermeditates. Thus,
M
4a 4b
2 3
M=H 38 71
Li 19 9
the oxaspiropentane from norbornanone (1) produces a mixture of two
cyclobutanones 2 and 3 whose ratio depends upon the nature of the acid
catalysis. With protonic acids, hke fluoroboric or hydrochloric acids, a
lower stereospecificity is observed than with Lewis acids like lithium per-
Chlorate.
The greater selectivity with lithium salts may be attributed to the faster
rate of cyclopropyl bond migration compared to rotation about the cyclo-
propyl carbon-norbornyl carbon bond in the carbonium ion intermediate
4a when greater electron density is on oxygen. Since this reaction anneals
a ring onto a carbonyl group with the production of spiro fused tings when
the carbonyl partner is a cyclic ketone, this process represents a single
member of a class of reactions termed spiroannelation. Johnson and cowor-
kers independently examined the reactions of dimethylaminophenyloxo-
sulfonium-cyclopropylide and reported a similar reaction in low yield. ~7
6
Sulfuranes in Organic Reactions and Synthesis
B. 7-Butyrolactone Synthesis
The ready availability of Cyclobutanones by this one step very high yield
process led to investigations of the Synthetic applications of such inter-
mediates. Oxidation to butyrolactones occurs readily and in yields of
70--90% utilizing either hypochlorous acidS, )0 or preferably basic hydro-
peroxide. )01,9
o
o 4
)4(
HOaN
52 C°
The reaction has the same characteristics as a Baeyer-Villager in that
the more substituted carbon preferentially migrates (see Eq. 4) and migra-
tion occurs with retention of configuration at the migrating carbon (see
Eq. 5). Thus, the overall synthetic event is to convert any carbonyl partner
o
(s)
+ ~ NaOH + ~
2H 02
52 'C°
into a 5-mono or 5,5-disubstituted-y-butyrolactone.
'R = 0 ~ R,~O
C, Geminal Alkylation )11
Cyclobutanones are very readily substituted at their alpha positions via
the corresponding enolates or enols. Thus, dibromination proceeds quanti-
tatively by the dropwise addition of two moles of molecular bromine in
%001. = B ~ 97% rB~.,,rB ~
02 aHC
5
7
B. .M Trost
carbon tetrachloride at room temperature. Methanolic sodium methoxide
effects ring cleavage at room temperature. The net result of this process
involves introduction of two functionally different alkyl groups onto a
carbonyl carbon -- thus the terminology geminal alkylation. Methyl 2,2-
~
O ~ ~R ,R
pentamethylene-4,4-dibromobutyric acid (5), the product from cyclo-
hexanone, illustrates some of the versatility of this approach. Silver ion
aHC O~CH 3 OHC
30NgA ~ H 20 =
HO FBH 4 )PahP( a IChR
CH 3
(98 )% (96 )%
promoted methanolysis effects replacement of the bromides by methoxides
with formation of an acetal. Acid hydrolysis frees the aldehyde functional
group. This latter compound, 2,2-pentamethylenesuccinaldehydic acid
methyl ester, was obtained in 86% overall yield from cyclohexanone.
Obviously either the aldehyde or the ester may be further functionalized
to generate a broad array of structural units. It must be noted that the
aldehyde readily decarbonylates using Wilkinson's catalyst in refluxing
acetonitrile. )21 Thus, this method even serves to convert a carbonyl group
to a ~-methyl carboxylic ester.
D. $ecoalkylation )81
The cyclobutanones derived from ~,~-epoxyketones present several unique
opportunities for further synthetic transformations. The oxaspiropentanes
are formed in over 90% yield by the cyclopropylide reaction under the
same conditions utilized previously. Rearrangement of the spiroepoxide in
the presence of a second epoxide eanbe carried out with aqueous fluoroboric
o
0 ~- 0 ------
3HC R aHC R 3HC
aHC ~HC aHC
Sulfuranes in Organic 3Reactions and Synthesis
),.r
II II
,_, ~ ~'-'I
z/u
C~
~ o
O
g
O
O
O
Scheme .1 Secoalkylation
acid in a two-phase system when the second epoxide is disubstituted,
e.g. 9, R = H. When this epoxide is trisubstituted, e.g. 9, R = CH3, oxalic
acid in acetonitrile is to be preferred. Addition of a nucleophile to the cyclo-
butane carbonyl creates a good leaving group three carbon atoms removed
from a good electron source, a negative oxygen.14,15} In the case of the
9