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Chelation or Non-Chelation Control in Addition Reactions of Chiral - and - Alkoxy Carbonyl Compounds [New Synthetic Methods (44)].

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1761 C. Rufer, E. Schroder, H. Gibian, Justus Liebigs Ann. Chem. 701 (1967)
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[78] a) H. Yamazaki, Y. Wakatsuki, Tetrahedron Lett. 1973, 3383; J. Chem.
SOC.Chem. Commun. 1973, 280; b) H. Bonnemann, R. Brinkmann, H.
Schenkluhn, Synthesis 1974, 575; c) R. A. Clement, US-Pat. 3829429
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Compounds, Val. 14, Part 3, Chapter XI, Wiley, New York 1974, p.
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[84] C. A. Parnell, K. P. C. Vollhardt, unpublished.
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[88] R. A. Earl, K. P. C. Vollhardt, unpublished and PhD thesis, University
of California, Berkeley 1983.
[89] P. Hong, H. Yamazaki, Tetrahedron Lett. 1977, 1333; Synthesis 1977, 50.
[90] R. A. Earl, K. P. C. Vollhardt, J . Am. Chem. Sac. 105 (1983) 6991.
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[95] a) M. C. Wani, P. E. Rowman, J. T. Lindley, M. E. Wall, J. Med. Chem.
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[96] a) H. Hoberg, B. W. Oster, J . Organomet. Chem. 234 (1982) C35; 252
(1983) 359; h) Synthesis 1982. 324.
[97] a) Y. Yamamoto, H. Yamazaki, Coord. Chem. Reu. 8 (1972) 225: b) Y.
Yamamoto, ibid. 32 (1980) 193.
[98] P. Pino, G. Braca in I. Wender, P. Pino: Organic Synthesis via Metal
Carbonyls, Vol. 2, Wiley, New York 1977, p. 419.
[99] a) H. Yamazaki, K. Aoki, Y. Yamamoto, Y. Wakatsuki, J. Am. Chem.
SOC.97 (1975) 3546; b) H. Yamazaki, Y. Wakatsuki, Bull. Chem. SOC.
Jpn. 52 (1979) 1239.
[I001 R. L. Brainard, K. P. C. Vollhardt, unpublished.
[I011 E. R. F. Gesing, J. P. Tane, K. P. C. Vollhardt, Angew. Chem. 92 (1980)
1057; Angew. Chem. Int. Ed. Engl. 19 (1980) 1023.
[I021 H. Kaulen, K. P. C. Vollhardt, unpublished.
[I031 a) R. Burt, M. Cooke, M. Green, J. Chem. SOC.A 1970, 2981; b) P. A.
Corrigan, R. S. Dickson, G. D. Fallon, L. J. Michel, C. Mok, Aust. J .
Chem. 31 (1978) 1937; c) P. A. Corrigan, R. S. Dickson, ibid. 32 (1979)
2147; d) P. A. Corrigan, R. S. Dickson, S. H. Johnson, G. N. Pain, M.
Yeoh, ibid. 35 (1982) 2203.
[I041 J. E. Sheats, J. Organornet. Chem. Libr. 7 (1979) 461.
[I051 J. P. Tane, K. P. C . Vollhardt, Angew. Chem. 94 (1982) 642: Angew.
Chem. Int. Ed. Engl. 21 (1982) 617; Angew. Chem. Suppl. 1982, 1360.
[I061 For reviews and recent studies see a) A. E. Greene, M.-J. Luche, J.-P.
Depres, J . Am. Chem. Sac. I05 (1983) 2435; b) M. Demuth, K. Schaffner, Angew. Chem. 94 (1982) 809; Angew. Chem. Int. Ed. Engl. 21
(1982) 820; c) B. M. Trost, Chem. Sor.Reu. 11 (1982) 141; a) L. A. Paquette, Top. Curr. Chem. 119 (1984) l .
(M*hud.l
Chelation or Non-Chelation Control in Addition Reactions of
Chiral a- and P-Alkoxy Carbonyl Compounds
New Synthetic
By Manfred T. Reetz*
The addition of C-nucleophiles such as Grignard reagents or enolates to chiral a- or p-alkoxy aldehydes or ketones creates a new center of chirality and is therefore diastereogenic.
In order to control stereoselectivity, two strategies have been developed: 1) Use of Lewisacidic reagents which form intermediate chelates, these being attacked stereoselectively
from the less hindered side (chelation control); 2) use of reagents incapable of chelation, stereoselective attack being governed by electronic and/or steric factors (non-chelation control).
Generally, the two methods lead to the opposite sense of diastereoselectivity. It is possible
to predict the outcome by careful choice of organometallic reagents containing elements
such as Li, Mg, B, Si, Sn, Cu, Zn, or Ti.
1. Introduction
The two n-faces of a carbony1 compound having at least
one chiral center are diastereotopic. Addition of C-nucleophiles such as Grignard reagents or enolates can therefore
lead to unequal amounts Of diastereomers. Reactions h volving such l,n-asYmmetric induction"b'cl have been
[*I Prof. Dr. M. T. Reetz
Fachbereich Chemie der Universitat
Hans-Meerwein-Strasse, D-3500 Marburg (FRG)
556
0 Verlag Chemie GmbH, 0-6940 Weinheim, 1984
termed "diastereofacially selective"[21.Although this phenomenon was observed as early as 1894['],it was not until
the work of Cram et al. that some degree of systematizaIn what is now known as Cram's
tion was
rule['], an a-chiral aldehyde (or ketone) such as I['] is assumed to adopt a conformation in which the largest of the
three a-substituents is antiperiplanar to the carbonyl function, nucleophilic attack then occurring from the less hin[*I Only one enantiomer is shown, although a racemate was used leading to
racemic products.
0570-0833/84/0808-0556 $ 02.50/0
Angew. Chem. Int. Ed. Engl. 23 (1984) 556-569
dered side. In the case of CH3MgBr, the ratio of Cram to
Beanti-Cram products 2 : 3 turned out to be ca. 66 :34"~~'.
sides the Cram model (cf. Newman projection 4), other explanations have been offered"]. Felkin et al. assumed a
a model which has been refined
reacting conformation 5[41,
by Anh, who postulated non-perpendicular attack (BiirgiDunitz trajectory), as shown in 6, on the basis of molecular orbital consideration^[^].
1
2
3
products)[']. The aldehydes 11, 13, and 15 (and the analogous ketones) react with Lewis acids to give the chelates
12, 14a, and 16, respectively, the arrows indicating the
preferred direction of attack. Instead of 14a, the other
half-chair conformation 14b can also be invoked. With the
dialkoxy aldehyde 17, a-coordination leads to 18 and pcoordination to 19, in which opposite diastereotopic faces
of the carbonyl group are exposed. Chelation in 19 is analogous to that in 14a, but diastereoselectivity might be expected to be enhanced because the non-complexed RO
group facilitates an "Anh-effect". For non-chelation control, it is clear that reagents not capable of bidentate complexation are necessary.
xo -
R'O
R""
TI
I, =
6
5
4
large, M =
M
II
11
12
medium, S = small substituent
For carbonyl compounds with a-halogen substituents,
Cornforth et al. proposed an electrostatic model in which
the electronegative group points away from the polar carbony1 function, i.e., it takes the place of L in 4['x6]. In contrast, Felkin et al. stated that "polar effects stabilize those
transition states in which the separation between the incoming nucleophile and the electronegative group is
greatest", as in 5 (L=electronegative group)'41.Anh's MO
calculations show that 6 (L = chlorine) is, in fact, the most
reactive conformation because n & o - o ~ _ c I interaction
provides a low-lying LUMO. Attack anti to L avoids certain anti-bonding interactions which occur in a syn-trajectory (see arrows in 6)['].
For a-alkoxy or hydroxy carbonyl compounds, the electronegative oxygen substituents exert potentially analogous effects. However, a different phenomenon is also possible, namely chelation, which makes the opposite n-face
sterically more accessible. In such cases, Cram's cyclic
model pertains[',31(see 8)['].
13
14b
OK' H
15
. 1\'1 .,
KO
p;
18
OR
17
19
M = metal
8
9
14a
;yy
Ph
7
H
\
K'O IVI
86
:
14
10
This review focuses on recent developments in controlling chelation or non-chelation in diastereogenic additions
to a - and p-alkoxy (and -hydroxy) aldehydes and ketones.
Several reviews covering certain aspects of chelation as
well as other types of "acyclic stereoselection" have appeared e l s e ~ h e r e [ ' ~ ~ * ~ ~ .
We shall call the respective dominant diastereomer chelation controlled or non-chelation controlled (Felkin-Anh
Angew. Chem. Int. Ed. Engl. 23 (1984) 556-569
Besides 1 ,masymmetric induction, a different type of
stereochemical problem may arise. If a C-nucleophile such
as an enolate is prochiral, addition to an achiral aldehyde
creates two new chiral centers by linkage of two sp2-hybridized C atoms. Diastereodifferentiation in such a process has been termed "simple diastereoselectivity", and
forms the basis of most of the recent work on aldol reactions[''] and related additions of crotylmetal compounds["].
If the aldehyde is chiral, such as 11, 13, 15, or 17, this
type of stereoselection and the problem of diastereofacial
selectivity (chelation or non-chelation) are both relevant.
Thus, a maximum offour diastereomers may be formed. In
the absence of special effects, the rules for predicting sim[*I
The latter has sometimes been called the anti-Cram product. However,
this may cause confusion because the term was first used for Cram's acyclic model (e.g., 1-2).
557
ple diastereoselection for achiral
also apply
to chiral compounds. Efficient methods for stereoselective
Grignard and aldol additions to chiral alkoxy carbonyl
compounds are of importance for the synthesis of natural
products, e.g. ionophores, pheromones, and carbohydrates[2’’’91.
2. Chelation-Controlled 1,2-Asymmetric Induction
2.1. Grignard, Alkyllithium, and Cuprate Reagents
In early work Cram et al.[3,71and later Stocker et a1.[12]
studied the addition of RMgX and RLi to a-alkoxy (and
hydroxy) carbonyl compounds and were able to rationalize
most of the data by assuming chelation of the type 12. The
ratio of chelation- to non-chelation-controlled products
ranged between 55 :45 and 96 :4. Exceptions were “explained” by invoking competition between cyclic, dipolar,
and open-chain models. Thereafter, further examples of
more or less useful levels of diastereoselectivity became
known[’.’31.Generally, low temperatures are beneficial, although the converse has been observed[’41.An example involving complete chelation control was reported by Kishi
et al., 20 -+21 being one of the key steps in their synthesis
of the isolasalocid ketone[”].
the old
However, if the chiral adjuvant is expenand Musive, this is unacceptable. Recently, Eliel et al.[93201
kaiyama et a1.[211have devised ingenious systems which
solve this problem. The starting point of Eliel’s strategy is
the conversion of 26 (available from (+)-pulegone) into
27. Grignard addition then occurs stereoselectively via aoxygen chelation to form 28. The fact that a-sulfur coordination does not compete was explained using the HSAB
principle. Aldehyde 30 ( > 90% ee) can be liberated and the
chiral starting material 31 recovered. Other 1,3-oxathianes
have also been described[’]. In the system studied by Mukaiyama et al., a-amino ketones in which proline derivatives are incorporated form the basis of chelation control[211.
21
26
28
29
30
I
21
20
Horton et al. have described reactions in which the
choice of protecting groups controls the sense of stereoselectivity[16]. Ketone 22 reacts with phenylmagnesium
bromide to form 23 via a-coordination; the p-oxygen carries a bulky silyl group which prevents competitive p-coordination. In case of 24, use of excess Grignard reagent first
deprotonates the hydroxy group, the intermediate Mg-alkoxy moiety then inducing p-chelation. A number of a-alkoxy and a-hydroxy aldehydes and ketones in steroids have
been shown to undergo pronounced chelation-controlled
Grignard-type additions[’.’71,but exceptions are known“’].
U
OH
In all these cases, the old and the newly created chiral
centers form part of the target molecule. It is also possible
to destroy the original chiral center via some sort of cleavage (sacrificial asymmetric synthesis). For example, several
groups have reported stereoselective Grignard additions to
certain carbohydrates followed by oxidative cleavage, a sequence which creates a new chiral center at the expense of
558
Since chelation control is not always effi~ient~’~’,’~],
Still
et al. carried out systematic studies in which the type of alkoxy group, the carbon nucleophile, solvent, and temperature were varied[221.It was found that ketones of the type
32 fail to react stereoselectively with alkyllithium reagents
(e.g., n-butyllithium), in contrast to Grignard compounds,
and that these reactions show dramatic solvent effects, tetrahydrofuran (THF) being the medium of choice.
The methoxyethoxymethyl (M EM) group has two additional oxygen atoms, so that chelation involving a “crownether effect” is conceivable. However, this appears not to
be necessary, since a-benzyloxy groups also facilitate complete chelation control. In their synthesis of the polyether
antibiotic monensin, Still et al. made use of these generalities to construct one of the building
Another elegant application pertains to the total synthesis of ( )-zoapatanol by Nicolaou et a1.i241.RLi sometimes reacts more
selectively than RMgX, a phenomenon which has not yet
been explained mechani~tically~’~’~.
+
Angew. Chem. 1111.Ed. Engl. 23 (1984) 556-569
Unfortunately, the extremely high levels of 1,2-asymmetric induction observed with ketones d o not extend to analogous aldehydesf2'], in line with previous ~tudies[*.~.'*~.
Perhaps this is due to the lower Lewis basicity of aldehydes. Thus, addition of CH3MgBr to aldehyde 35 affords
36 9 1
35
9 37
ing an additional chiral center at the P-position. Thus, 44
shows the usual diastereofacial selectivity with
(CH3),CuLi ( >95 :5), whereas 46 gives a product ratio of
2 : lL2'].Although the authors d o not provide a reason for
this dramatic difference, chelation of 46 in a manner analogous to 45 gives rise to 47a, in which the axial p-methyl
group hinders the incoming nucleophile. An alternative
conformation 47b, in which the two methyl groups are
equatorial, is also likely to react less stereoselectively than
45.
I< = C:H,OCH,Ph
36 and 37 in the ratio 91 :9. Since this was the only aldehyde studied, it is not clear whether the benzylmethoxy
group is necessary for the attainment of this level of selectivity.
Later experiments showed that the choice of reaction
conditions, type of protecting group, and Grignard reagent
are crucial, as evidenced by the fact that the a-benzyloxy
analogue of 35 reacts with CH3MgI fairly unselectively
(60 :40 ratio)[261.Addition of Grignard reagents to 38 provides another example[271.
It
R = CFIzOCII,Ph
47a
R
Ph
Ph
39
60
40
40
Recently, further examples of low levels of chelation
control in the addition of Grignard reagents to chiral a-alkoxy aldehydes have been reported; these include compounds having various types of alkoxy groups such as me~~~.
thoxymethyl (MOM) and pyran m o i e t i e ~ [ ' ~ ,Clearly,
other approaches to this problem are necessary (Section
2.3).
If we now consider p-coordination (see 14), compounds
of the type 41 do not react stereoselectively with RMgX or
RLi, in contrast to cup rate^[^']. For example, (CH3)2CuLi
adds to 41a to afford 42a and 43a in the ratio 97 :3. The
benzyloxy analogue 41b reacts only slightly less selectively.
However, chelation-directed diastereoselectivity is not observed if the oxygen atom in the alkoxy residue is sufficiently hindered, as in the 0-trityl derivative 4 1 ~ ' ~ ~ ~ .
41
a, R
= CH,OCH,Ph
b, 11 = CII,Ph
c, K = CPh,
42
43
97
95
= 33
3
5
67
It is unclear why cuprates, but not RMgX or RLi, lead to
efficient P-chelation[2'1. Nevertheless, 14 is a useful model
since it also predicts stereoselectivity for compounds havAngew. Chem. Int. Ed. Engl. 23 (1984) 556-569
= CHzOCTizPh; M
47b
= mt.ta1
In summary, notable advances have been made in inducing chelation with the aid of RMgX, RLi, and R2CuLi.
However, a number of problems persist, and the present
level of mechanistic understanding is unsatisfactory. The
role played by the aggregation state of the reagents or type
of solvent are poorly understood. In carbohydrate chemistry (Section 5), the situation is sometimes even less clear.
2.2. Aldol Additions with
Lithium- and Magnesium-Enolates
With a few exceptions, lithium enolates add to a-alkoxy
aldehydes either completely unselectively or show some
degree of non-chelation control1"'] (Section 4). For example, 48 reacts with the ester enolate 49 without any diastereofacial selectivity"'].
48
49
50
!iO
:
50
51
In contrast, certain p-alkoxy aldehydes having centers of
chirality at the a-or @-positiondisplay useful levels of chelation control, as shown by Masamune et al.[291;since they
used prochiral enolates, simple diastereoselectivity is also
involved. Several aldehydes 52 were allowed to react with
559
54
20
22
17
10
13
8
7
5
60 undergoes chemo- and stereoselective C-C bond forming reactions with carbonyl compounds[301and SN1-active
alkyl halides[311.Some of these reactions depend upon the
pronounced Lewis acidity of 60. Furthermore, 60 as well
as titanium tetrachloride 61 readily form octahedral complexes with two donor molecules (e.g., ether, THF) or with
bidentate ligand system^'^'-^^^. These observations set the
stage for testing Lewis-acidic titanium reagents in chelation-controlled reactions of alkoxy carbonyl compounds.
60
H3(:TiC1,
TiC1,
61
Addition of 60 (prepared quantitatively from dimethylzinc and TiC14 in CH2Clz)to the aldehyde 48 led to 63 and
64 in the ratio 92 :8, consistent with an intermediate of the
type 62lz6].
enolates 53, leading mainly to 54 and 55, in addition to
small amounts of the other two possible diastereomers.
The preferred formation of 54 was explained by assuming
coordination of the lithium cation by three oxygen atoms,
as shown in 56, rather than the sterically less favorable
transition state 57. This hypothesis neglects the state of aggregation of the enolates, but is nevertheless useful. Simple
diastereoselectivity is syn (Masamune nomenclature) and
depends upon the configuration of the enolate[”].
Chelation control in the reaction of 58 with the lithium
enolate of ketone 59 is not as efficient (product ratio
75 :25)[291.Apparently, stereoselectivity is only pronounced
if the system is “loaded” with additional groups at the 8position, as in 52 (R’ = alkyl). This is plausible on the basis
of the model shown in 56. Chelation control is expected to
decrease if the relative stereochemistry of the two chiral
centers in 52 is reversed, but this has not been tested (cf.
44 vs. 46).
I---$r-a-
CH,
H
(O
CH, 071(CH3)2
tBu
Ph
58, R = CH20CH2CH2SiMe3
59
Why do a- and P-alkoxy aldehydes show such different
behavior in classical aldol additions? Perhaps the Masamune decalin-like transition state in the p-case is energetically favored relative to the more strained hydrindane-like
transition state which would have to be transversed in case
of a-alkoxy aldehydes. It should be noted that lithium enolates derived from esters generally do not show chelation
effects in reactions with P-alkoxy aldehydes (Section 4),
the reason for this being unclear”’]. Systematic studies involving magnesium enolates have not appeared[231,although in one case chelation seems to be slightly better
compared to the lithium analogue[291.
48
62
6 3 $12
:
8
64
48 can also be “tied up” by TiC14 and selectively alkylated by adding mild C-nucleophiles such as dialkylzinc,
allylsilanes, or allylstannanes which do not destroy chelation (e.g., 48 -+ 65)IZ6].For comparison, allylmagnesium
chloride reacts with 48 to afford 65b and 66b in the ratio
60 :40. In the addition of allylsilanes, we found the somewhat milder SnCl, to be equally well s ~ i t e d [ ~ ’as
* ~also
~~,
TiCI4 and SnC1, are similar
reported by Heathcock et al.1371.
in that both are capable of forming six-coordinate octahedral complexes[341.Interestingly, MgBr,-etherate in CHzCl,
(- 30°C/3 h) also promotes this reaction, but the stereoselectivity (70 :30) and conversion (ca. 50%) are inferior[361.
One equivalent of A12C16(AICl, is dimeric in solution) affords 65b and 66b in the ratio 85 : 15 (CH2Cl2/-78”C/3
h; ca. 80% conversion)[361.In contrast, BF3 is incapable of
chelating, and in fact causes reversal of diastereoselectivity
(Section 4).
65
a, R = nRu
1)0
b, R = CFIiCH=CI12
>93
e, R = CH2C(Me)=CI12 >‘I5
66
10
<7
<5
2.3. Other Organometallic Reagents
In early studies devoted to the application of organotitanium reagents to organic synthesis, we discovered that
560
Silyl enol ethers 67 are also excellent C-nucleophileslz6].
This is synthetically important, because they constitute the
Angew. Chem. I n l . Ed. Engl. 23 (1984) 556-569
participation of the open-chain transition states 78 and
79.
+
61
69
68
a , R' = IT, It2 = P h
b, 11' = 11, It2 = IRu
c, 11' = CH3, 112 = OCH,
9 (i
4
>95
<:,
<7
>97
only currently known class of compounds for chelation-controlled aldol additions to a-alkoxy aldehydes.
In view of this, it was of interest to determine how prochiral silyl enol ethers behave. In the reaction of the complex 48/TiC14 with pure 70a, essentially only one of four
possible diastereomers is formed[261.The X-ray structure determination of 71 shows that it is the chelation-controlled
product in which simple diastereoselectivity is syn. Since
the Mukaiyama aldol addition involving normal aldehydes
is known to be n o n - ~ e l e c t i v e(e.g.,
~ ~ ~70a
~ reacts with propanal/TiCl, to form a 66 :34 syn/anti-rnixt~re[~~]),
this stereoselection is remarkable. 48/SnCI4+ 70a gives the same
result[261.Activation of an aldehyde RCHO by Lewis acids
is generally assumed to occur by complexation to the carbony1 group anti to the R group (Section 6); however, chelation necessarily involves syn-complexation, and this may
be the determining factor for the unexpectedly high simple
diastereoselectivity. This special effect was first observed
in reactions of P-chiral, P-alkoxy aldehydes1391(Section 3)
and thus appears to be general. Indeed, the influence of
chelation on simple diastereoselectivity is also apparent in
the reaction of the achirul aldehyde 75. For a-chelation,
SnCI, is often more efficient than TiC1,1401.
The lithium (2)-enolate corresponding to 70a shows
non-chelation control (71 :72 : 73 :74 = 10 :60 :30 :0), and
the zinc analogue is non-selective (1 1 :23 :50 : 16 ratio).
Addition of preformed trichlorotitanium enolate (generated by adding TiCI, to 70a) results in chelation control:
(71 : 72 : 73 : 74 = 89 :8 :3 :O). In order to gain further mechanistic information, 48/TiCI4 was allowed to react with
the (E)-isomer 70b'401.The product distribution 85 :0 :0 : 15
shows that complete chelation control again pertains, and
that the sense of simple diastereoselectivity is independent
of the configuration of the silyl enol ether. This suggests
97
85
b, E-isomer
Fh
yo
L o
H
1 MC14
2
70a
75
P
f0
CH3
Ph
Table 1. Stereoselective formation of X I [a].
R'
1
CH,
CH,
tBu
tBu
CH3
CH3
tBu
2
3
4
5
6
7
h
P
+
Z :E
Lewis
acid
Chelation:
non-chelation
1 7 : 83
17 : 83
>99 : < 1
>99: < I
5 : 95
95: 5
> 9 9 : <1
TiC14
Sn('14
TiCl4
Sn('ll
>99
>99
89
88
20
26
21
-
: 1
: 1
: I1
: 12
: 80
: 74
: 79
Simple
diastereoselectivity
(syn :anti)
23
20
65
66
69
84
66
: 77
: 80
: 35
: 34
: 31
: 16
: 34
[a] Entries 1-4: silyl enol ether 80 and Lewis acids in CHICll; entries 5 and
7: Li.enolates in THF; entry 6: THF~hexame~hylphosphor~c
triamide
( H M ~ all
, reactions at -78°C (conversion ~ 8 5 % ) .
(non-chelationlanti)
P
((,helation/anti)
0
a
0
15
h
f0
Ph
76
77
11C14
90
10
SnC14
95
5
Anyew. Chem. Int. Ed. Enyl. 23 (1984) 556 -569
Entry
3
0
g
81
( M = Ti, Sn)
(non-chelationlsyn)
(chelation / s y n )
a, %-isomer
Although this and alternative models correctly predict
chelation control, the prediction of the sense of simple
diastereoselectivity is more d i f f i ~ u l t [ ~Not
~ ~only
~ ~ ] the
. methyl group of the enolates 70, but also the relative steric
bulk of the other two enolate substituents exert steric influence. For example, replacing the phenyl group in 70a
by ethyl, reverses simple diastereoselectivity, i.e., the (2)silyl enol ether from 3-pentanone reacts with 48/TiC14
with complete chelation control, but the simple diastereoselectivity is anti (anti/syn = 82 : 18)[361.Furthermore, a
(Z)/(E)-mixture of 66 :34 leads to an anti/syn distribution
of 56 :44. The influence of different enolate substituents is
also apparent in ester additions (Table 1)1361.Included are
the lithium enolates, which afford Felkin-Anh products
561
preferentially (titanium enolates are better suited, as discussed in Section 4).
An important example illustrating the usefulness of the
present methodology involves the addition of silyl enol
ether 82 to 48/SnC14, which results in a single diastereomer 8314']. The lithium enolate affords a mixture[''], and
48/TiC14/82 fails to
83
82
In the B-alkoxy series, chelation-controlled aldol additions involving 84 are also possible, e.g., by using the silyl
enol ethers 67b and 67c from pinacolone or isobutyric
acid esterc4'].Allylsilane additions are slightly less selective[35,37,411
92, li = n-C,Tf9
'
93 91
9
:
94
shown by Keck et al.[421.Since the stereochemistry of Lewis
acid-mediated addition of crotylstannane to achiral aldehydes is known to be syn["],good chelation control a n d
simple diastereoselectivity in the reaction of 92 to 93/94
come as no surprise.
A ZnBr,-mediated Grignard reaction has been reported,
but its generality is unknown[431.Allylzinc or -tin reagents
(in the absence of catalysts) have not been investigated in a
systematic way, but Kishi et al. reported interesting results
for aldehydes of the type 95[441.Depending on its state of
purity, diallylzinc reacts with 95 to afford 96 and 97 in the
ratios 82 : 18 to 94 :6. The CH2=CHCH21/SnC12 system is
96
\Ph
84
+
Ph
Ph
/
/
95
97
85
a, I I =~ 1-1, tt2 = t ~ u
b, R' = CH,, R2 = OCH,
93
>97
86
5
:
<3
Prochiral 70a adds to 84 with complete chelation control, simple diastereoselectivity also being excellent
(syn :anti = 9 1 :9)[401.The other two diastereomers are not
formed. Again, chelation boosts simple diastereoselectivity. 89 also adds to 84 with chelation control, but not with
any degree of simple diastereosele~tivity[~~~.
89
87 9 1
9
88
90 50
50
91
In summary, TiC14- or SnCl,-induced additions of R,Zn,
silyl enol ethers, or allylsilanes to a- and S-alkoxy aldehydes have emerged as a powerful synthetic tool, and further progress involving other nucleophiles and/or more
complicated aldehydes and ketones with two chiral centers
is likely. In fact, allyl- and crotylstannanes add to a-alkoxy
aldehydes in chelation-controlled processes mediated by
Lewis acids such as TiCI4, MgX,, or ZnX,, as recently
562
even more selective (96 :4). A chair trans-decalin-type of
transition state 98 is believed to be involved, in contrast to
the energetically less favorable boat analogue 99 or cisdecalin-like conformations[441.In 95 and in similar com-
pounds, the relative configuration of the chiral centers is
expected to influence the degree of chelation control. Such
effects are indeed observed and can be
With the exception of RLi and RMgX, little is known
about the addition of organometallics to alkoxy ketones.
Methylzirconium and -titanium reagents add to a-alkoxy
ketones with levels of chelation control which equal or surpass analogous reactions with RMgX[45,461.
Angew. Chem. Int. Ed. Engl. 23 (1984) 556-569
3. Chelation-Controlled
1,3- and 1,4-Asymmetric Inductions
Control of 1,3-asymmetric induction in Grignard and aldo1 additions to acyclic carbonyl compounds of the type
100 is not possible using reagents such as RMgX, RLi,
R,CuLi, lithium enolates, or allylboron c o m p o u n d ~ [ ~
We were able to solve this problem in the same manner as
in 1,2-stereocontrol, i. e. by employing Lewis-acidic titanium reagents (Section 2.3). Thus, 100 is converted into 102
with unprecedented diastereofacial selectivity[3y1(Table 2).
Based on these observations, it was subsequently found
that SnCI, is also a useful Lewis acid for allylsilane additions[35.371
R’TICI,
70a
70 b
94
5
90
10
Complete 1,3-asymmetric induction is also possible using the bis(trimethylsily1) enol ether 111, which adds to
100a/TiC14 to afford only two of four possible diastereomers ( > 70 :30). Both products are chelation controlled,
but the simple diastereoselectivity has not been elucidated‘3h1.
__j
- 78 O C
Ph
In order to explore the effect of chelation on simple
diastereoselectivity, reactions of chelated achiral 3-benzyloxypropanal 108 with ( Z ) - and ( E ) - 7 0 were preformed.
Stereoselectivity is independent of the enolate configuration. This is in accord with an “acyclic” approach of the silyl enol ether to 108 (see Section 2.3), but certainly does
~ ~ ~not
~ ~prove
~ ~ Isuch
.
a mechanism.
Ph
Ph
(0
100a/TiC14 +
OH 0
IT3C+Ci13
HO CH,
Table 2. 1,3-Asyrnrnetric induction in addition reactions of 100 [39].
Reagent [a]
R‘
RZ
CH3TiC13
TiCI4/CHz=CHCH2SiMe3
TiCI4/CH2=C(CH3)CH2SiMei
TiC14/Zn(n-C4H9)z
CH3TiC13
TiCI,/CH2=CHCH2SiMe3
TiC14/CH2=C(CH,)CH2SiMe,
CH3
CH3
CHI
CH3
n-C4H,
n-C4H9
n-C4H9
CH3
CHz=CHCH2
CHz=C(CH,)CHZ
n-C4H9
CH3
CH2=CHCH2
CH*=C(CH,)CH2
111
90
95
95
90
91
95
: 10
: 5
: 5
: 10
: 9
: 5
99 : 1
The idea that allyl- and crotylmetal reagents can be used
as “masked enolates” has been developed by Hoffmann et
a1.[”,481.
We have applied this strategy to perform iterative
additions. For example, the allyl adduct 113 (prepared on
[a] All reactions at -78°C in CHzC12;for TiCI4, complexation and reaction
at -78°C.
Th
\o
100.a
The use of silyl enol ethers facilitates 1,3-asymmetric induction in aldol reactions for the first timei3’]. Remarkably,
70a adds to 100a/TiC14 to provide essentially only one
(106) of four diastereomers. Simple diastereoselectivity is
syn. 100a/SnC14 affords three diastereomers ; p-chelation
is thus more effective with TiCI,.
I ’h
Ptl
70a
(0
+
(
106
CIl3
11,
‘12
Angew. Chem. I n t . Ed. Engl. 23 (1984) 556-569
:
TI&
Ph
OH
A
113
I
I!’h
Ph
Bh
------,
‘0
114
Ph Ph
/
115
116
114
>91
<9
an 80 mmol scale in 92% yield and in >99% isomeric purity after one distillation) was 0-benzylated and ozonized,
and the product 114 again subjected to chelation-controlled additions (-78”C/5 min; conversion > 8 5 Y 0 ) [ ~ ~ !
Repetitive 1,3-stereorelations involving hydroxy groups
occur in certain natural product^^^'].
C)
l13c4Ph
olr
011
11,(
112
102 : 103
$1
107
563
Strategies relating to intramolecular transfer of C-nucleophiles. such as 119+ 123, are beginning to be considered.
119 reacts with tetraallylzirconium to afford 123 in 81%
diastereo~electivity[~~~.
Ph
L o
Ph
L O
OH
fI,C+HoCH,
OH
f ( , c , , o H , , , ~+
H
H
CH,
6 3 8
92
:
H
64
H,CTi(OCHMe,),
128 5
122
9 5 129
In view of these results, reaction of 127 with ketones
such as 130 came as a surprise[4h1.In this case the ratio of
products 131 and 132 ( > 98 : < 2) is the same as in the addition of CH3TiCI3or CH3MgCl to 130! Either ketones are
such strong Lewis bases that even 127 participates in che-
123
Several cases of 1.Casvmmetric induction based on seven-membered chelates have been s t ~ d i e d [ ' ~ , ~e.g.,
~],
124 + 125 + 126[261.
Allylsilane addition to 124 is 75% stereo~eIective[~~].
Ph
Ph
\-0
L o
I
-
b
OH
127_ , . ~ , ~ , , c ~ i , ~ ~ ,
?,,H0
H,C
CH2CH3
TI
+ H 3 C > , , H , ,C, ,H3
II,(
C'H,
TI
I30
Ph
Ph
011
131
(~HzCH,
>98
<2
:
132
1 TC14
Hc,,,c
133c'h,o
2 (CHhZn
FI
124
Ph
Ph
(0
(0
+
€I,C L C H 3
OH
H,(:/CYC~~
125 85
OH
1 5 126
4. Non-Chelation-Controlled Additions
Non-chelation control is a formidable task because there
is no general way to reduce the number of degrees of freedom of non-complexed molecules. Reagents incapable of
chelation must be used and electronic and/or steric factors
relied upon, notably those defined by the Felkin-Anh or
Cornforth (dipolar) models. In fact, u p till now reversal of
diastereoselectivity in favor of non-chelation has only
proved feasible for 1,2-asymmetric induction.
Since the Lewis acidity of alkyltitanium reagents decreases drastically in going from RTiCI3 to RTi(OR')3[5'~5'1,
we speculated that the latter might be incapable of chelation. Indeed, the complex CH3Ti(OCHMe2)3 127 reacts
with 48 to afford preferentially the Felkin-Anh product 64
(63 :64 = 8 :92)[261.Presently, this is the only CH3-metal
compound known which permits non-chelation control.
Thus, chelation or non-chelation control is possible in a
predictable way simply by varying the ligands at titanium
(CH3TiC13 affords a 92 :8 ratio; Section 2.3). For a-acetoxy aldehydes, stereo- and chemoselectivity is observed,
as in the formation of 129I5O1.This methylation method is
general and has been applied to carbohydrates (Section 5).
The Felkin-Anh model (or possibly the Cornforth hypothesis) provides a satisfactory explanation.
564
lation, o r some other conformation is involved. Actually,
theory predicts greater 1,2-asymmetric induction (FelkinAnh-products) for ketones compared to aldehydes, because the nteietone
MO lies higher in energy than the na*ldehyde
MO, making n&o-o&x mixing more important[521.
Titanium enolates of low Lewis-acidity react with chiral
a-alkoxy aldehydes via non-chelation control[261.A case in
point is the addition of 133 to 48, which affords only two
of the four possible diastereomers"]. This is another example of reversal of diastereoselectivity by substitution of
chloro by alkoxy ligands at titanium. Simple diastereoselectivity is syn, as in reactions with achiral aldehyde~[~'.~''].
Ph
48
133
71 1 <
:
87
72
Sometimes tris(diethy1arnino)titanium enolates are better suited. With 134, 93% non-chelation control and > 90%
simple diastereoselectivity are observed[361. The corresponding Li-enolate affords all four diastereomers (Table
l), as does the triisopropoxytitanium analogue
(135 : 136 : 137 : 138 = 14 : 33 : 35 : 18)[361.Other Li-enolates
show modest levels of non-chelation control""]. In these
[*] The configurational assignment with regard to simple diastereoselectivity
in the formation of the major isomer 72 has now been ascertained by
chemical correlation [41].
Angew. Chem. Inr. Ed. Engl. 23 (1984) 556-569
48
OTi(NEt,),
OH
+
H3C&i02/Bu
-7 8 T
i
Ph
134
OH
OH
H 3 C ~ O z t B u 1 f 3 ~ O Z / B u IT3(:
f
Ph
135
(non-chelationlanti)
85
8
cases, Heathcock et al. have performed elegant experiments involving optically active enolates in order to increase diastereofacial selectivity[s31.The principle of double stereodifferentiation seems promising in this area.
A different approach to non-chelation control involves
ammonium enolates. Using Noyori's method of fluoride
ion induced aldol additions[541,we allowed 48 to react with
70a under conditions of kinetic control and observed only
two of the four diastereomers with 82% non-chelation control and 100% simple diastereoselectivity (syn)["]. It remains to be seen to what extent this method can be generalized.
nBu4NFITHF
-78OCIl h
71 + 72 + 73 + 74
1 8 : 82
: 0
:
P1-1
137
(non-chelationlsyn)
7
-
Ph
136
(chelation /syn)
48 + 70a
+
CH,
0
A third strategy makes use of Lewis acids which are incapable of chelation. By using two equivalents of gaseous
BF,, double complexation of 11, 13, and 15 might be expected to result in formation of adducts 139, 140, and 141
with rigid conformations due to electrostatic
Nucleophilic attack from the less hindered side in 141 simulates chelation control, and this has been verified experimentally[351.In contrast, 139 and 140 are expected to
form products of non-chelation control.
138
(chelationlanti)
0
pentanal). For a-chiral, b-doxy aldehydes, reaction with
crotylstannanes results in excellent non-chelation control
and simple diastereoselectivity (syn)["].
142
143
a, R = CTI,Ph
b, X = SitRuMe,
(i1
>!)I
144
39
i s
Although allylboron compounds might be expected to
exhibit non-chelation control, selectivity in the reaction of
a-benzyloxy propanal 48 with 2-allyl-4,4,5,5-tetramethyl1,3,2-dioxaborolane is meager (65b : 66b = 35 :65)["]. However, in sugar chemistry, aldehydes react very selectively
with certain allylboron compounds (Section 5).
Finally, several special cases of non-chelation control in
the addition of Li- and Mg-enolates to certain a-chiral, palkoxy (or siloxy) aldehydes have been reported. These include key steps in the synthesis of erythromycin A by
Woodward et a1.lS6],maytansinoids by Meyers et al.["], and
monensin by StiN et al.[231.Nevertheless, there are not
enough data to draw up general guidelines for enolate
reactions of this type"']. For non-chelation, Cram's rule
may be applied.
5. Addition Reactions in Carbohydrate Chemistry
141
Indeed, addition of allyltrimethylsilane or the silyl enol
ethers 67b and 67c to 139 ( - 95 "C/1 h) results in significant levels of non-chelation control (65b :66b = 20 :80,
68b : 69b = 10 :90 and 68c : 69c = 16 :84)[411.Addition of
67b to 140 results in a product distribution
85a : 86b = 12 :88, which is again synonymous with nonBF3.Et20 is considerably less effichelation
cient. Besides the "Cornforth conformations", 139 and
140, the results are also consistent with Anh's theory[411.
Keck et al. have shown that allylstannanes also undergo
BF3-mediated non-chelation-controlled additions'421. For
the bulky aldehyde 142, the tert-butyldimethylsilyl protecting group results in higher selectivity than the benzyl
group. However, useful stereoselectivity is not observed
with other a-alkoxy or a-siloxy aldehydes (e.g., a-siloxy
Anaew. Chem. l n t . Ed. Enal. 23 (1984) 556-569
Although some of the general points mentioned in this
article also apply to carbohydrate aldehydes and ketones,
additional factors often have to be considered. Surprises
and mechanistic uncertainties prevail in a number of situations. For example, Grignard additions to the mannofuranose 145 follow different stereochemical pathways, depending upon whether EtMgBr or HC=CMgBr is used[58].
In contrast, 146 reacts with benzylmagnesium chloride to
provide a single diastereomer having the D-allo-configurationfs9].
In other cases, interpretation of the stereoselectivity using Cram's cyclic model is straightforward. For example,
several
have described chelation-controlled
565
Grignard additions to D-galactose derivatives (e.g. 147)1611.
According to Schollkopf, a-chelation with the oxygen
atoms of the carbonyl group and the pyran ring determines
the sense of diastereofacial selectivity[611.
H
155
154
147
'
148
H3CMgBr
+Li
'
149
80
20
>98
<2
OEt
Similarly, Hanessian et a1.[62a1
and
postulate chelation of the type shown in 151 to explain the preferred
formation of 152 in the Grignard addition to 1501621.
Coordination with the less basic b-benzyloxy group cannot
compete effectively. In order to "turn off' chelation and
thus to reverse diastereofacial selectivity, we performed the
reaction with CH3Ti(OCHMe2)3[261.
Exclusive formation of
the Felkin-Anh product 153 is in accord with the non-chelation control observed with other aldehydes (Section 4),
and documents the synthetic value of this methodolo-
without any complexation to the a- or b-oxygen. p-Chelation 156 has also been postulated and leads to a synergistic effect (type 19). However, a Cornforth-type of conformation 157 also accommodates the data.
Mukaiyama et al. have published a series of papers in
this area[641.For example, in their synthesis of D-ribdose,
addition to 154 constitutes the key step[651.Table 3 shows
that ZnX,-mediated reactions are best. Although the nature of the actual reacting organometallic species is not
known, 156 (M = Zn) was postulated.
Table 3. Stereoselective reaction or 154 to 159/ 160.
gy126,501.
MX2/MX4 [a]
T I"C1
-
MgBr2
SnCI4
ZnCI,
ZnBr,
Zn12
150, R = CH,Ph
+
-i
H,CMgBr
H3CTi(OCHMe,),
Yield [%]
78
68
0
0
49
0
0
0
159 : 160
40 : 6 0
50 : 5 0
95 : 5
58
60
75
57
90 :10
95 : 5
95 : 5
[a] All reactions in THF, except the SnCI,-mediated addition (toluene).
151
HQo CH3
153
152
88
:
12
<1
:
>99
2,3-O-Isopropylidene-~-glyceraldehyde
154 or its enantiomer as well as similar compounds have been allowed to
react with a large number of Grignard reagents and enolates. Up to about 1980, most of the reactions reported
were fairly u n s e l e ~ t i v e ~Since
' ~ ~ ~then
~ ~ . enormous progress
has been made by careful choice of reagents and conditions. These reactions are often the starting point of natural products syntheses. The diastereofacial selectivity of
the reactions is anti (Masamune nomenclature)[*1and has
generally been explained by the Felkin-Anh model 155
The stereoselective introduction of methyl groups into
154 is very difficult[h31. We therefore employed
CH3Ti(OCHMe2)3in the hope of effecting non-chelation
control. The ratio of anti :syn-adducts was in fact 75 :25
(THF/ - 78 "C/5 h; > 85%)conversion)[661,which is not exceedingly good, but better than in previous methodsr631.
Mulzer et al. have used organotitanium reagents to add
other groupsr671.Oddly, the phenyltitanium reagent 161d
favors the syn-adduct 163d, which is a rare exception in
nucleophilic additions to 154. Mulzer et al. have also studied other organometallic reagents (Li, Mg, Zn, and Cr) and
discuss various models, including tridentate chelation involving the aldehyde function and both alkoxy groups[671.
162
a , K = CH,
[*I The syn/anti-nomenclature is used both for the diastereofacial selectivity
and for simple diastereoselectivity [Ic].
566
157
156
b, R
=
It
=
C ,
d, R
nl3u
CII2;('IICl12
= Ph
75
110
71
9
163
:
:
:
:
25
10
29
91
Angrw. Chem. Int. Ed. Engl. 23 (1984) 556-569
Considerable effort has gone into adding ally1 groups to
154. Although diallylzinc affords a 91 :9 ratio of
162c : 1 6 3 ~ [ ~a~better
],
result is reached using boron reagents. Hojjmann et al. have shown that switching from 164
to optically active 165 increases the 162c : 163c ratio from
80 :20 to 96 :4[681.
x
The optically active crotylboron reagents 166 and 169
have also been tested["]. The former delivers one (167) of
four diastereomers, the latter a mixture of 170 and 171.
Whereas simple diastereoselectivity depends in a predictable way on the configuration of the crotyl double
b ~ n d [ ~ ~ the
, ~ ' ]phenomenon
,
behind the different degrees
of diastereofacial selectivity is not easily pinpointed. With
racemic 169, the 170 : 171 ratio dropped to 67 :33, which
shows that double stereodifferentiation is involved. Preliminary reactions involving other aldehydes indicate that
the Anh model is not necessarily the optimal explanatie#"]. Perhaps the reactions of allylboron compounds
can be viewed as cycloadditions in which there is little
flow of electron density from the reagent to the aldeh~de[~~].
k
167 > 98
154
:
> 2 168
\
\
HdH
H' 0 1 1
Ph
CH3
170
72
:
28
171
169
154 has also been used in other stereoselective addition~[~"].
Certain enolates are anti-selective to a greater or
lesser e~tent['~,*'~.
Electrochemically generated dichloroacetate enolates add very selectively, as described by Shono
et al.[7'1. In all cases the Felkin-Anh model 155 was invoked to explain the stereoselectivity.
anti-Stereochemistry is also generally observed for Bsubstituted substrates of the type 172 and 173. For the
trans-isomer 172, the same phenomena should operate as
in 154. The cis-compound 173 is different, because transition states of the type 155 or 156 would involve unfavorable steric interactions between the incoming nucleophile
and the methyl group, an aspect which has not been discussed in the literature. It seems that a Cornforth-type of
conformation 174 is a more plausible explanation for the
observed anti-selectivity.
Angew. Chem. Int. Ed. Engl. 23 (1984) 556-569
t n
172
173
174
Fuganti et al. have reported many elegant additions of
diallylzinc or propargylzinc reagents to 172 and 173 as
well as to imine analogues[72'.The stereoselective formation of 175 and 177 are typical examples.
Ph
CH3
x
9 P
172
x0
(CH2=CHCH2)2Zn
0
>
H,C
175
95
:
5
176
177
95
:
5
178
This method has been used for the synthesis of various
natural products. An outstanding example is the synthesis
of the amino sugars L-daunosamine and L-ristosamine
from the phenylsulfenimines derived from 172 and 173,
respectively[731.Roush et al. used allylboron compounds["]
to synthesize D-fucose deri~atives'~~'.
An exception to the
general rule regarding anti-stereoselection has recently
been published, but not explained[751.Also, ketones related
to 154 react with RMgX to form preferentially syn-adPerhaps this involves chelation of the more basic
ketone oxygen and the a-alkoxy group.
Finally, a number of related processes have been reported. These include hetero-Diels-Alder reactions of 154
as described by Danishefsky et al.[771.Furthermore, Wittig
reactions of 154 yield olefins, which have been used in stereoselective Diels-Alder reactions[781,1,3-dipolar cycloadd i t i ~ n s [ ~ ~cyclopropanation
],
induced by phosphorus
ylideslsol, as well as Michael additions''']. The observed
1,2-asymmetric induction can be explained on the basis of
the Houk-model["21, which has some similarity to the Anhtheory.
6. Mechanistic Studies
Despite the synthetic progress in chelation and non-chelation control, shortcomings persist in terms of the mechanism. For example, the products of chelation control are
usually rationalized solely on the basis of the stereochemical outcome. Until recently, no direct physical evidence for
intermediate chelates had been presented. Although X-ray
structural data on such species have not yet been completed, 'H- and 13C-NMRspectroscopic studies have been
performed[26*661.
Thus, the NMR data for 179 (which reacts
100% stereoselectively with allylsilanes)[261and 180 are
consistent with the proposed structures.
567
Finally, Hoffmann et al. have carried out reactions based
on the principle of double stere~differentiation['~l.
Whereas the optically active ally1 boronate 186 reacts with
154 to form the anti-adduct 187, diastereofacial selectivity
is reversed if the enantiomer 188 is employed!
H
I
t0.
,
c H3
Although a host of Lewis acid adducts with carbonyl
compounds are
no X-ray crystallographic data
on ketone o r aldehyde complexes are available[831.Since
the question of syn- or anti-complexation of aldehydes is
of mechanistic importance, Rademacher et al. performed
some MNDO calculations on the BF,-adduct of acetaldehyde["]. The difference in energy between the anti- (181)
and syn-adduct (183) is only ca. 2 kcal/mol. The linear
form 182 shows n o minimum, but n-coordination has not
yet been explored. Recently, Helmchen came upon the latter phenomenon in a n X-ray crystallographic study of a
TiCl,-diester a d d ~ c t [ ' ~ ]Clearly,
.
more work is necessary
before details of mechanistic hypotheses become meaningful.
H3C
H3c
FO,,
H
,--"
BF3
181
-
297. 07
pO...BE.,
€I
*
H
182
- 291.79
-
183
295.21
Mf [ k c a l / m o l ]
7. Conclusions and Addendum
A variety of reliable methods for chelation control in nucleophilic additions to chiral a- and B-alkoxy carbonyl
compounds are available. Further elaborations are certain
to follow, including the use of synthetically useful C-nucleophiles not previously tested. A more difficult task is
the development of new and better ways of non-chelation
control. As far as predictive guidelines for the latter are
concerned, any one of the qualitative models (Felkin, Anh,
or Cornforth) may be used. It is a challenge to devise experiments which illuminate the real mechanism in a given
case.
Since the submission of this manuscript, further progress has been made. A steroidal a-alkoxy aldehyde has
been allowed to react with a lithium dienolate under conditions of chelation control, and the aldol adduct converted into withanolide D[*'l. In an extension of their work
on cyclocondensations of aldehydes with dienes of the
type 184, Danishefsky et al. have reported chelation-directed asymmetric C-C-bond forming reactions, e.g. the
synthesis of 185[''I.
568
c1
154
\
Our work was supported by the Deutsche Forschungsgerneinschaft a n d the Fonds der Chemischen Industrie. I would
like to thank Prof. R. W. Hoffmann for helpful discussions.
My thanks are also due to my co-workers, especially K. Kesseler, A . Jung, S. Schmidtberger, a n d R. Steinbach.
Received: June 4, 1984 [A 500 IE]
German version: Angew. Chem. 96 (1984) 542
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569
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