The stereochemistry of a retro-carbolithiation reaction

Article abstract of DOI:10.1039/a808410f

Ring-opening of the cyclopropylmethyl lithium compound 7 to give the α-duryl thio-substituted alkyllithium compound 8 proceeds in a stereochemically defined manner at the lithium-bearing stereocentre.

Full text of DOI:10.1039/a808410f

The stereochemistry of a retro-carbolithiation reaction
Reinhard W. Hoffmann and Ralf Koberstein
Fachbereich Chemie der Philipps-Universität Marburg, Hans-Meerwein-Strasse, 35032 Marburg, Germany.
E-mail: rwho@ps1515.chemie.uni-marburg.de
Received (in Liverpool, UK) 29th October 1998, Accepted 17th November 1998
Li
Ring-opening of the cyclopropylmethyl lithium compound 7
SeMe
i
to give the a-duryl thio-substituted alkyllithium compound
DurS
ii
DurS
8 proceeds in a stereochemically defined manner at the
lithium-bearing stereocentre.
7
6
The stereochemical course of reactions in which organolithium
compounds are generated may reveal fundamental details of
organolithium chemistry. For instance, tin–lithium exchange to
generate alkyllithium compounds has been found to proceed
with retention of configuration.1–3 The carbolithiation of vinyl
sulfides has been shown to proceed in a non-stereospecific
manner.4 Here we would like to address the stereochemistry of
a retro-carbolithiation reaction, the ring-opening of cyclopro-
pylmethyl lithium compounds. The prototype of this rearrange-
ment (1?2) was shown by Lansbury5 to proceed at 270 °C
with a half life of 53 min in Et2O (Scheme 1).
+
+
H
H
DurS
DurS
DurS
DurS
Li
Li
8b
iii
8a
H
H
Sn
Sn
The related ring-opening of 3 should create a chiral
organolithium compound 4. This would allow the determination
of the stereochemistry in the generation of the new carbon–
lithium bond, provided that the resulting organolithium com-
pound 4 is configurationally stable and the regioselectivity of
the ring opening is such as to generate compound 4 and not the
isomer 5. We surmised that both conditions would be met when
X is a durylthio group. a-Durylthio alkyllithium compounds are
configurationally stable at 2110 °C4 and stabilization of the
negative charge by a sulfur substituent should direct the ring
opening of 3 to give 4. There remains, however, the necessity to
effect the ring opening at 2110 °C. We surmised that breaking
of the carbon–lithium bond in 3 would be rate determining.
Therefore, a delocalized allylic system at the migration origin
should facilitate this process. This led us to investigate the ring-
opening of the lithium compound 7, generated by a low
temperature selenium–lithium exchange reaction.6
The seleno ether 6 of 90% ee (determined by Mosher ester
analysis of the precursor 14) was treated with ButLi at 2107 °C
in THF in a two-compartment low temperature reaction vessel
(Scheme 2).7 The organolithium compound 7 formed in this
manner immediately underwent ring opening, since quenching
with (2)-menthyl(dimethyl)tin bromide 92,8 after 30 min led to
the tin compounds 10a and 10b in a 9:1 E/Z ratio (67% yield).
119Sn NMR analysis revealed that the major E-isomer was
formed with 76% diastereomeric excess. Quenching after 10 or
60 min, or quenching with the enantiomeric reagent ent-9,
generated the tin compounds with a constant de in the range of
76–82%. This shows that the organolithium compound 8 is
configurationally stable under the conditions applied, and that
10a
10b
SnBr
9
Scheme 2 Reagents and conditions: i, ButLi, THF, 2107 °C; ii, 2107 °C,
30 min; iii, 9.
quenching of 8 with 9 is not complicated by kinetic resolu-
tion.
In order to determine the stereochemistry of the ring opening
process, pre-cooled MeI was added to the organolithium
compound 8 after 30 min at 2107 °C (Scheme 3). This resulted
in 88% of a 88:12 E/Z mixture of the hexadienyl thioether 11.
Hydrogenation of the mixture provided uniform dextrorotatory
2-durylthiopentane 12. The optical purity and the absolute
configuration of 12 was determined with the aid of a sample
prepared from (S)-heptan-2-ol.
+
H
H
Li
DurS
DurS
DurS
Li
i
8a
8b
+
H
H
DurS
CH3
11a
CH3
11b
Li
ii
Li
1
3
2
Li
DurS
X
+
X
Li
[α]D +7.3
[α]D +9.2
CH3
12
Li
X
4
5
HO
iii
12
X =
S
= DurS-
CH3
Scheme 3 Reagents and conditions: i, MeI; ii, H2, (Ph3P)3RhCl; iii, MsCl,
Scheme 1
pyridine; iv, DurSLi.
Chem. Commun., 1999, 33–34
33

converted to 15 and on to the selenoether 6 in a series of
standard transformations (Swern oxidation, Horner olefination,
DIBAL-H reduction).
We are grateful to the Deutsche Forschungsgemeinschaft
(SFB 260) and the Fonds der Chemischen Industrie for support
of this study.
i
Bu3Sn
OH
Bu3Sn
14 (90% ee)
OH
13
ii
iii,iv
6
DurS
OH
DurS
OH
15
Notes and references
CONMe2
CONMe2
O
O
1 W. C. Still and C. Sreekumar, J. Am. Chem. Soc., 1980, 102, 1201; J. S.
Sawyer, A. Kucerovy, T. L. Macdonald and G. J. McGarvey, J. Am.
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N. H. Phillips, J. Am. Chem. Soc., 1992, 114, 6577.
2 F. Hammerschmidt, A. Hanninger and H. Völlenkle, Chem. Eur. J.,
1997, 3, 1728.
Bu
B
16
Scheme 4 Reagents and conditions: i, 16, Zn(CH2I)2·DME; ii, BunLi,
(DurS)2; iii, BunLi, TsCl; iv, MeSeLi.
3 For an exception and for leading references, see: J. Clayden and J. H.
Pink, Tetrahedron Lett., 1997, 38, 2565.
4 R. W. Hoffmann, R. Koberstein, B. Remacle and A. Krief, Chem.
Commun., 1997, 2189.
5 P. T. Lansbury, V. A. Pattison, W. A. Clement and J. D. Sidler, J. Am.
Chem. Soc., 1964, 86, 2247; cf. also. A. B. Charette and J. Naud,
Tetrahedron Lett., 1998, 39, 7259.
6 H. Gilman and R. L. Bebb, J. Am. Chem. Soc., 1939, 61, 109; H. Gilman
and F. J. Webb, J. Am. Chem. Soc., 1949, 71, 4062; D. Seebach and N.
Peleties, Angew. Chem., 1969, 81, 465; Angew. Chem., Int. Ed. Engl.,
1969, 8, 450; M. Clarembeau and A. Krief., Tetrahedron Lett., 1984, 25,
3629.
7 H. C. Stiasny and R. W. Hoffmann, Chem. Eur. J., 1995, 619.
8 H. Schumann and B. C. Wassermann, J. Organomet. Chem., 1989, 365,
C1.
9 Electrophilic ring opening of cyclopropanes both with retention and
inversion of configuration has precedent: D. H. Gibson and C. H.
DePuy, Chem. Rev., 1974, 74, 605.
10 D. Hoppe and T. Hense, Angew. Chem., 1997, 109, 2376; Angew.
Chem., Int. Ed. Engl., 1997, 36, 2282; for an exception see: R. E.
Gawley and Q. Zhang, J. Org. Chem., 1995, 60, 5763.
11 A. B. Charette, S. Prescott and C. Brochu, J. Org. Chem., 1995, 60,
1081.
The optical purity of 12 (ca. 80% o.p.) corresponds to the de
values of the tin compounds 10 and shows that the ring opening
of 7 to give 8 proceeds with at most 10% loss of enantiomeric
composition. The minor loss in enantiomeric purity of 8 during
its generation at 2107 °C from 7 should be associated with the
ring opening process of 7.9
Knowledge of the absolute configuration of the starting
material 6 and that of the product 11 shows that the overall
transformation proceeds with retention of configuration at the
sulfur-bearing carbon atom. There is, however, some element of
uncertainty regarding the stereochemistry of the individual
steps. It is generally accepted10 that the methylation of ‘low
reactive’ sp3-hybridized organolithium compounds by MeI
proceeds with retention of configuration. If this applies also to
the transformation of 8 into 11 it follows that the ring opening
of 7 to give 8 proceeds with predominant retention of
configuration at the lithium-bearing carbon atom.
The synthesis of the starting material 6 relied on the
asymmetric cyclopropanation developed by Charette.11 Cyclo-
propanation of 13 should furnish the cyclopropane 14 of the
absolute configuration shown (Scheme 4). The latter was then
Communication 8/08410F
34
Chem. Commun., 1999, 33–34