Stereoselective Synthesis and Retentive Trapping of α-Chiral Secondary Alkyllithiums Leading to Stereodefined α,β-Dimethyl Carboxylic Esters

Article abstract of DOI:10.1002/chem.201601911

The treatment of α-chiral secondary alkyl iodides with tBuLi at ?100 °C leads to the corresponding secondary alkyllithiums with high retention of configuration. Subsequent quenching with various electrophiles such as Bu₂S₂, DMF, MeOB(OR)₂, or Et₂CO provides the desired products with retention of configuration. Furthermore, a transmetalation with CuBr?P(OEt)₃also allows retentive trapping with acid chlorides and ethylene oxide. The quenching of the resulting alkyllithiums with ClCO₂Et furnishes stereoselectively syn- and anti-ethyl-2,3-dimethyl ester carboxylates (d.r.>94 %). Related esters bearing three adjacent stereo-controlled centers (stereotriads) have also been prepared. This method has been applied to the synthesis of the ant pheromone (±)-lasiol in 26 % overall yield (four steps) with d.r.=97:3 starting from commercially available cis-2,3-epoxybutane.

Full text of DOI:10.1002/chem.201601911

DOI: 10.1002/chem.201601911
Communication
&
Lithium Reagents
Stereoselective Synthesis and Retentive Trapping of a-Chiral
Secondary Alkyllithiums Leading to Stereodefined a,b-Dimethyl
Carboxylic Esters
Varvara Morozova, Kohei Moriya, Peter Mayer, and Paul Knochel*[a]
Abstract: The treatment of a-chiral secondary alkyl io-
dides with tBuLi at À1008C leads to the corresponding
secondary alkyllithiums with high retention of configura-
tion. Subsequent quenching with various electrophiles
such as Bu2S2, DMF, MeOB(OR)2, or Et2CO provides the de-
sired products with retention of configuration. Further-
more, a transmetalation with CuBr·P(OEt)3 also allows re-
tentive trapping with acid chlorides and ethylene oxide.
The quenching of the resulting alkyllithiums with ClCO2Et
furnishes stereoselectively syn- and anti-ethyl-2,3-dimethyl
ester carboxylates (d.r.>94%). Related esters bearing
Scheme 1. The retrosynthetical analysis of anti- and syn-2,3-dimethylcarboxy-
three adjacent stereo-controlled centers (stereotriads)
late derivatives (1) (top), and diastereoselective generation of a-chiral anti-
and syn-secondary alkyllithiums (2) from the secondary alkyl iodides (3)
have also been prepared. This method has been applied
to the synthesis of the ant pheromone (Æ)-lasiol in 26%
(bottom).
overall yield (four steps) with d.r.=97:3 starting from com-
mercially available cis-2,3-epoxybutane.
Here, we wish to report a highly stereoselective preparation
of various a-chiral alkyllithiums of type 2 starting from the cor-
responding iodides, and their application to the stereoselective
The preparation of chiral organometallic building blocks is
useful for the stereoselective construction of acyclic natural
products bearing several adjacent chiral centers.[1] For example,
the diastereoselective synthesis of 2,3-dimethylcarboxylate de-
rivatives of type 1, encountered in complex natural products,[2]
may be performed using a diastereoselective 1,4-addition/alkyl-
ation. This retrosynthesis has often been used but has several
drawbacks, such as the degree of diastereoselectivity, and
access to both anti- and syn-isomers of 1.[2] Alternatively, one
can envision the use of a carboxylation of the chiral organo-
lithium reagents of type 2 with ClCO2Et for preparing esters of
type 1 stereoselectively (Scheme 1). Although acyclic hetero-
atom-stabilized chiral lithium reagents are well known,[3,4] non-
stabilized secondary alkyllithiums have been less extensively
studied.[3c] Recently, we reported that an I–Li-exchange allows
the generation of functionalized secondary alkyllithium re-
agents bearing remote functionalities (at position 3 or 4).[5] Ste-
reoselective transmetalations further extend the synthetic
scope of these organometallic intermediates.[6]
preparation of 2,3-dimethylcarboxylates of type 1. We have
also extended this method to the preparation of chiral lithium
derivatives bearing three adjacent stereocenters (stereotri-
ads).[7]
Thus, the treatment of diastereomerically enriched anti-alkyl
iodide (anti-3a, d.r.=98:2) with tBuLi (inverse addition) in hex-
ane:ether (3:2) at À1008C (5 min) provides the intermediate
lithium reagent (anti-2a) (Scheme 2). This isomer was trapped
[5]
with Bu2S2 (2 equiv, À1008C, 10 s) leading to the anti-thioeth-
er (anti-4a) in 61% yield and with d.r.=96:4, showing a high
retention of the configuration.[5b] Similarly, the reaction of the
secondary alkyl iodide (syn-3a, d.r.=2:98) with tBuLi, under
the same conditions, followed by quenching with Bu2S2, gives
the syn-thioether (syn-4a) in 81% yield and d.r.=4:96, indicat-
ing again a high retention for this electrophilic substitution.
This reaction sequence was extended to other electrophiles
such as MeOBpin[5b,c] (MeOBpin=2-methoxy-4,4,5,5-tetra-
methyl-1,3,2-dioxaborolane) leading to the boronic esters (anti-
4b and syn-4b,[8] entries 1 and 2 of Table 1) in 60 and 83%
yield, as well as 98 and 99% retention of configuration, respec-
tively.[9] Reactions of the lithium reagents anti-2a and syn-2a
with DMF[5b,c] produced the anti- and syn-aldehydes (anti-4c
and syn-4c, entries 3 and 4) in 60 and 70% yield with 93 and
95% retention of configuration, respectively. The preparation
of tertiary alcohols anti-4d (d.r.=97:3, 71% yield) and syn-4d
(d.r.=8:92, 50% yield) was achieved by the addition of alkyl-
[a] V. Morozova, Dr. K. Moriya, Dr. P. Mayer, Prof. Dr. P. Knochel
Department Chemie, Ludwig-Maximilians-Universitꢀt Mꢁnchen
Butenandtstrasse 5–13, 81377 Mꢁnchen (Germany)
E-mail: Paul.Knochel@cup.uni-muenchen.de
Supporting information for this article is available on the WWW under
http://dx.doi.org/10.1002/chem.201601911.
Chem. Eur. J. 2016, 22, 1 – 5
1
ꢀ 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
&
&
These are not the final page numbers! ÞÞ

Communication
P(OEt)3 (Scheme 3).[11] The resulting secondary alkylcopper re-
agent (anti-5) obtained from the alkyl iodide (anti-3a, d.r.=
99:1) gives after acylation with PhCOCl the anti-ketone (anti-
6a) in 62% yield and d.r.=96:4. Similarly, the syn-iodide (syn-
3a, d.r.=2:98) undergoes a smooth I–Li-exchange and, after
transmetalation with CuBr·P(OEt)3, leads to the copper reagent
(syn-5). Benzoylation of syn-5 affords the syn-ketone (syn-6a) in
48% yield (d.r.=10:90; Scheme 3). Interestingly, the retentive
transmetalation to copper also allows the opening of ethylene
oxide[12] with anti- and syn-5. In the case of the less sterically
hindered copper reagent (anti-5), a satisfying retention is ob-
served in the formation of the alcohol anti-6b (d.r.=92:8, 57%
yield). However, in the case of the more sterically congested
syn-5 (compare with Scheme 1), an erosion of the diastereose-
lectivity was observed and the desired alcohol syn-6b was ob-
tained in 43% yield with a moderate d.r. of 26:74. This lower
diastereoselectivity can be explained by the somewhat lower
reactivity of ethylene oxide, leading to a competitive configu-
rational isomerization of syn-5 (Scheme 3).[12]
Scheme 2. Stereoselective preparation of anti- and syn-thioethers (anti-4a
and syn-4a) from corresponding anti- and syn-alkyl iodides (anti-3a and syn-
3a, respectively), through I–Li-exchange and subsequent trapping with
Bu2S2.
lithiums anti-2a and syn-2a to Et2CO, respectively.[3f,5b,c,10] Most
importantly, the use of ClCO2Et[5b,c] as an electrophile in this se-
quence afforded the ethyl-2,3-dimethylcarboxylic esters anti-
1a (d.r.=97:3) and syn-1a (d.r.=9:91) in 75 and 82% yields
(entries 7 and 8), respectively. In all cases, high levels of reten-
tive substitutions were found (>94% retention).[9]
The electrophile scope can be further extended using a trans-
metalation with the hexane-soluble copper complex CuBr·-
Table 1. Diastereoselective reactions of anti- and syn- acyclic secondary
alkyllithium 2a with electrophiles leading to products of type 4 and 1.
Entry Li-reagent (d.r)[a] Electrophile Product
Yield [%] (d.r.)[b]
1
2
anti-2a (99:1)
syn-2a (5:95)
MeOBpin
MeOBpin
83 (99:1)
anti-4b
60 (6:94)
Scheme 3. Stereoselective formation of alkylcopper reagents anti-5 and syn-
5 from the alkyl iodides anti-3a and syn-3a, respectively, through I–Li-ex-
change, transmetalation with CuBr·P(OEt)3, and subsequent reactions with
electrophiles.
syn-4b
anti-4c
syn-4c
3
4
anti-2a (99:1)
syn-2a (1:99)
DMF
DMF
60 (95:5)
70 (7:93)
With this method in hand, we have prepared a range of
both anti- and syn-2,3-dimethyl-substituted carboxylates of
type 1 starting from readily available alkyl iodides of type 3.[14]
Thus, the anti-alkyllithium (2b), prepared from the correspond-
ing alkyl iodide (anti-3b, d.r.=99:1), was treated at À1008C
under standard conditions with ClCO2Et leading to the anti-
ethyl-2,3-dimethylcarboxylate (anti-1b) in 86% yield and d.r.=
97:3 (Table 2, entry 1). Similarly, the syn-alkyl iodide (syn-3b,
d.r.=1:99) was converted by this sequence to the syn-2,3-di-
methylcarboxylate (syn-1b) in 63% yield and d.r.=5:95
(entry 2). Several additional functionalities such as a triple
bond or double bond are perfectly tolerated, as well as a pro-
tected hydroxyl group. For example, the anti-alkyl iodide (anti-
3c, d.r.=99:1) bearing a triple carbon–carbon bond in the g-
position was converted to the corresponding anti-ethyl-2,3-di-
methylcarboxylic ester (anti-1c) in 72% yield and d.r.=97:3
(entry 3). The other diastereomer (syn-1c) was obtained from
the syn-alkyl iodide (syn-3c, d.r.=1:99) under the same condi-
5
6
anti-2a (99:1)
syn-2a (2:98)
EtCOEt
EtCOEt
71 (97:3)
50 (8:92)
anti-4d
syn-4d
anti-1a
syn-1a
7
8
anti-2a (99:1)
syn-2a (5:95)
ClCO2Et
ClCO2Et
82 (97:3)
75 (9:91)
[a] Diastereomeric ratio of the corresponding iodides (anti-3a and syn-
3a) given in parentheses. [b] The diastereomeric ratio was determined by
NMR analysis.
&
&
Chem. Eur. J. 2016, 22, 1 – 5
www.chemeurj.org
2
ꢀ 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
ÝÝ These are not the final page numbers!

Communication
tions in 61% yield and d.r.=1:99 (entry 4). The treatment of
anti-alkyl iodide (anti-3d, d.r.=97:3) containing a remote
double bond with tBuLi under standard conditions afforded
the anti-alkyllithium 2d, which was then treated with ClCO2Et
to provide the anti-carboxylic derivative (anti-1d) in 64% yield
and d.r.=96:4 (entry 5). A lower retention of configuration was
observed in the preparation of the syn-carboxylate 1d from
the syn-alkyl iodide (syn-3d, d.r.=5:95). Thus, the ester (syn-
1d) was isolated in 69% yield with d.r.=9:91 (entry 6). The
anti- and syn-benzyloxy-protected alkyl iodides (anti-3e, d.r.=
96:4; and syn-3e, d.r.=5:95) were converted to the corre-
sponding anti- and syn-carboxylic esters (anti-1e and syn-1e)
in the same manner in 77 and 60% yield (d.r.=91:9 and d.r.=
10:90; entries 7 and 8), respectively. The anti- and syn- alkyl io-
dides bearing an OTBS-group (TBS=tert-butyldimethylsilyl) at
the g-position (anti-3 f, d.r.=97:3; and syn-3 f, d.r.=5:95) were
treated under the same conditions to afford anti-2 f and syn-
2 f, both of which reacted with ClCO2Et leading to the ethyl-
2,3-dimethylcarboxylic esters anti-1 f in 72% yield with d.r=
94:6, and syn-1 f in 59% yield and d.r.=8:92 (entries 9 and 10,
respectively). Thus, in all cases the retention is higher than
94%. The best results are obtained from anti-lithium reagents,
whereas the syn-alkyllithiums, which are more sterically con-
gested (Scheme 1) and less configurationally stable, lead to
somewhat lower diastereoselectivities (Table 2, entries 2, 6, 8,
and 10).
Table 2. Diastereoselective synthesis of anti- and syn-ethyl-2,3-dimethyl
carboxylates 1b–f from the alkyl iodides 3b–f by I–Li-exchange and fol-
lowing trapping with ClCO2Et after 5 seconds.
Entry
1
Iodide[a]
Li-reagent
anti-2b
syn-2b
Product and Yield[a]
anti-1b, 86% (97:3)
syn-1b, 63% (5:95)
anti-1c, 72% (97:3)
anti-3b (99:1)
syn-3b (1:99)
anti-3c (99:1)
2
3
anti-2c
4
syn-3c (1:99)
anti-3d (97:3)
syn-3d (5:95)
anti-3e (96:4)
syn-3e (5:95)
anti-3 f (97:3)
syn-3 f (5:95)
syn-2c
anti-2d
syn-2d
anti-2e
syn-2e
anti-2 f
syn-2 f
syn-1c, 61% (1:99)
anti-1d, 64%, (96:4)
syn-1d, 69% (9:91)
anti-1e, 77% (91:9)
syn-1e, 60% (10:90)
anti-1 f, 72% (94:6)
syn-1 f, 59% (8:92)
5
6
Our approach can be extended to the preparation of stereo-
triads.[7] Thus, the reaction of the two diastereomeric alkyl io-
dides 7 and 8 bearing three adjacent stereocenters are con-
verted with retention of configuration through an I–Li-ex-
change, followed by a quenching with Bu2S2, which leads to
the thioethers 9 and 10 in 50 and 53% yield and diastereose-
lectivities of 97:3 and 3:97, respectively (Scheme 4). As an ap-
plication, the alkyl iodide 7 was transformed into the corre-
sponding ethyl ester 11 (by reaction with tBuLi and then
ClCO2Et) with 57% overall yield and d.r.=99:1. The lactoniza-
tion of 11 furnishes the lactone 12 in 90% yield and d.r.=
99:1[14] (Scheme 4).
7
8
9
10
We have also prepared an ant sex pheromone, (Æ)-lasiol[15]
(alcohol 13), in four steps and 26% overall yield starting from
[a] The diastereomeric ratio, given in parentheses, was determined by
NMR analysis.
the commercially available cis-2,3-epoxybutane 14. First, epox-
ide opening with prenylmagnesium chloride[16] in the presence
of CuI,[12c,17] followed by an Appel reaction[5,18] furnishes the
secondary alkyl iodide 15 in 48% yield (d.r.=97:3,
Scheme 5).[19] The alkyl iodide 15 was converted to (Æ)-lasiol
(13) in three more steps : I–Li-exchange, quenching with
ClCO2Et, followed by LiAlH4 reduction provided (Æ)-lasiol (13)
in 55% overall yield and d.r.=97:3.
In summary, we have reported a retentive I–Li-exchange re-
action of a-chiral secondary iodides leading to chiral secondary
alkyllithium building blocks, which were used to prepare vari-
ous 2,3-dimethyl carboxylic ester derivatives often encountered
in natural product targets with high diastereoselectivity. We
have extended our method to the stereoselective preparation
Scheme 4. Stereoselective synthesis of stereotriads.
Chem. Eur. J. 2016, 22, 1 – 5
www.chemeurj.org
3
ꢀ 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
&
&
These are not the final page numbers! ÞÞ

Communication
Angew. Chem. 2013, 125, 8170; i) R. Mansueto, F. M. Perna, A. Salomone,
S. Florio, V. Capriati, Chem. Commun. 2013, 49, 4911; j) A. Salomone,
F. M. Perna, A. Falcicchio, S. O. Nilsson Lill, A. Moliterni, R. Michel, S.
Florio, D. Stalke, V. Capriati, Chem. Sci. 2014, 5, 528; k) X. Li, I. Coldham,
J. Am. Chem. Soc. 2014, 136, 5551.
[5] a) S. Seel, G. Dagousset, T. Thaler, A. Frischmuth, K. Karaghiosoff, H.
Zipse, P. Knochel, Chem. Eur. J. 2013, 19, 4614; b) G. Dagousset, K.
Moriya, R. Mose, G. Berionni, P. Knochel, Angew. Chem. Int. Ed. 2014, 53,
1425; Angew. Chem. 2014, 126, 1449; c) K. Moriya, D. Didier, M. Simon,
J. M. Hammann, G. Berionni, K. Karaghiosoff, H. Zipse, H. Mayr, P. Kno-
chel, Angew. Chem. Int. Ed. 2015, 54, 2754; Angew. Chem. 2015, 127,
2793.
[6] a) M. Gardette, A. Alexakis, J. F. Normant, Tetrahedron Lett. 1982, 23,
5155; b) D. Stead, P. O’Brien, A. J. Sanderson, Org. Lett. 2005, 7, 4459;
c) I. Coldham, D. Leonori, J. Org. Chem. 2010, 75, 4069; d) T. K. Beng,
R. E. Gawley, Org. Lett. 2011, 13, 394; e) K. Moriya, M. Simon, R. Mose, K.
Karaghiosoff, P. Knochel, Angew. Chem. Int. Ed. 2015, 54, 10963; Angew.
Chem. 2015, 127, 11113; f) M. FaÇanꢂs-Mastral, R. Vitale, M. Pꢄrez, B. L.
Feringa, Chem. Eur. J. 2015, 21, 4209; g) D. Heijnen, J. Gualtierotti, V.
Hornillos, B. L. Feringa, Chem. Eur. J. 2016, 22, 3991.
Scheme 5. Diastereoselective synthesis of (Æ)-lasiol (13) from cis-2,3-epoxy-
butane (14).
of carboxylic derivatives bearing stereotriads, and have also
prepared the sex ant pheromone (Æ)-lasiol. Further applica-
tions are currently being investigated in our laboratory.
Acknowledgements
We thank the Deutsche Forschungsgemeinschaft (SFB 749,
B02) for financial support. We also thank Rockwood Lithium
GmbH (Hoechst) and BASF SE (Ludwigshafen) for generous gift
of chemicals. We thank Dr. Dorian Didier for preliminary experi-
ments.
[7] a) I. Paterson, O. Delgado, G. J. Florence, I. Lyothier, M. O’Brien, J. P.
Scott, N. Sereinig, J. Org. Chem. 2005, 70, 150; b) S. Laclef, M. Turks, P.
Vogel, Angew. Chem. Int. Ed. 2010, 49, 8525; Angew. Chem. 2010, 122,
8704; c) M. Chen, W. R. Roush, J. Am. Chem. Soc. 2012, 134, 3925; d) S.
Ho, C. Bucher, J. L. Leighton, Angew. Chem. Int. Ed. 2013, 52, 6757;
Angew. Chem. 2013, 125, 6889.
[8] X-ray crystallographic analysis of the syn-4b confirmed the syn- relative
stereochemistry.
[9] The percentage of the racemization was calculated in the following
way: (0.95À0.94)/(0.95)ꢅ100=1.1%.
Keywords: carboxylic acids · copper · lithium · pheromone ·
stereotriads
[10] D. M. Hodgson, P. G. Humphreys, J. G. Ward, Org. Lett. 2005, 7, 1153.
[11] a) F. E. Ziegler, K. Mikami, Tetrahedron Lett. 1984, 25, 131; b) M. Gardette,
A. Alexakis, J. F. Normant, Tetrahedron 1985, 41, 5887; c) F. Pꢄrez-Balde-
ras, M. Ortega-MuÇoz, J. Morales-Sanfrutos, F. Hernꢂndez-Mateo, F. G.
Calvo-Flores, J. A. Calvo-Asꢃn, J. Isac-Garcꢃa, F. Santoyo-Gonzꢂlez, Org.
Lett. 2003, 5, 1951; d) L. I. Kursheva, O. N. Kataeva, D. B. Krivolapov, A. T.
Gubaidullin, E. S. Batyeva, O. G. Sinyashin, Heteroat. Chem. 2008, 19,
483.
[12] a) A. Ghribi, A. Alexakis, J. F. Normant, Tetrahedron Lett. 1984, 25, 3075;
b) A. Alexakis, D. Jachiet, J. F. Normant, Tetrahedron 1986, 42, 5607;
c) S. F. Martin, J. R. Fishpaugh, J. M. Power, D. M. Giolando, R. A. Jones,
C. M. Nunn, A. H. Cowley, J. Am. Chem. Soc. 1988, 110, 7226.
[13] For details see Supporting Information.
[14] a) R. Bꢄnꢄteau, J. Lebreton, F. Dꢄnꢆs, Chem. Asian J. 2012, 7, 1516; b) W.
Ren, Y. Bian, Z. Zhang, H. Shang, P. Zhang, Y. Chen, Z. Yang, T. Luo, Y.
Tang, Angew. Chem. Int. Ed. 2012, 51, 6984; Angew. Chem. 2012, 124,
7090.
[15] a) H. A. Lloyd, T. H. Jones, A. Hefetz, J. Tengç, Tetrahedron Lett. 1990, 31,
5559; b) A. W. Van Zijl, W. Szymanski, F. Lꢇpez, A. J. Minnaard, B. L. Ferin-
ga, J. Org. Chem. 2008, 73, 6994; c) J. Zhao, K. Burgess, J. Am. Chem.
Soc. 2009, 131, 13236.
[1] a) J. Clayden, Organolithiums: Selectivity for Synthesis (Eds.: J. E. Baldwin,
R. M. Williams), Pergamon, Oxford, 2002; b) The Chemistry of Organo-
lithium Compounds (Eds.: Z. Rappoport, I. Marek), Wiley, Chichester,
2004; c) Stereochemical Aspects of Organolithium Compounds (Eds.: R. E.
Gawley, J. S. Siegel), VHCA, Zꢁrich, 2010; d) G. Eppe, D. Didier, I. Marek,
Chem. Rev. 2015, 115, 9175.
[2] a) T. Baba, G. Huang, M. Isobe, Tetrahedron 2003, 59, 6851; b) D. Domon,
K. Fujiwara, Y. Ohtaniuchi, A. Takezawa, S. Takeda, H. Kawasaki, A. Murai,
H. Kawai, T. Suzuki, Tetrahedron Lett. 2005, 46, 8279; c) H. Takamura, N.
Nishiuma, T. Abe, I. Kadota, Org. Lett. 2011, 13, 4704.
[3] a) D. Hoppe, T. Hense, Angew. Chem. Int. Ed. Engl. 1997, 36, 2282;
Angew. Chem. 1997, 109, 2376; b) S. D. Rychnovsky, A. J. Buckmelter,
V. H. Dahanukar, D. J. Skalitzky, J. Org. Chem. 1999, 64, 6849; c) C.
Serino, N. Stehle, Y. S. Park, S. Florio, P. Beak, J. Org. Chem. 1999, 64,
1160; d) I. Coldham, S. Dufour, T. F. N. Haxell, J. J. Patel, G. Sanchez-Jime-
nez, J. Am. Chem. Soc. 2006, 128, 10943; e) D. C. Kapeller, L. Brecker, F.
Hammerschmidt, Chem. Eur. J. 2007, 13, 9582; f) F. Foubelo, M. Yus,
Chem. Soc. Rev. 2008, 37, 2620; g) D. C. Kapeller, F. Hammerschmidt,
Chem. Eur. J. 2009, 15, 5729; h) J. J. Gammon, V. H. Gessner, G. R. Barker,
J. Granander, A. C. Whitwood, C. Strohmann, P. O’Brien, B. Kelly, J. Am.
Chem. Soc. 2010, 132, 13922; i) V. Capriati, S. Florio, F. M. Perna, A. Salo-
mone, Chem. Eur. J. 2010, 16, 9778; j) T. K. Beng, J. S. Woo, R. E. Gawley,
J. Am. Chem. Soc. 2012, 134, 14764; k) V. Capriati, F. M. Perna, A. Salo-
mone, Dalton Trans. 2014, 43, 14204.
[16] M. Nasuda, M. Ohmori, K. Ohyama, Y. Fujimoto, Chem. Pharm. Bull.
2012, 60, 681.
[17] C. Huynh, F. Derguini-Boumechal, G. Linstrumelle, Tetrahedron Lett.
1979, 20, 1503.
[4] a) M. D. Curtis, P. Beak, J. Org. Chem. 1999, 64, 2996; b) D. C. Kapeller, F.
Hammerschmidt, J. Am. Chem. Soc. 2008, 130, 2329; c) R. J. Bahde, S. D.
Rychnovsky, Org. Lett. 2008, 10, 4017; d) P. OÇa Burgos, I. Fernꢂndez,
M. J. Iglesias, S. Garcꢃa-Granda, F. L. Ortiz, Org. Lett. 2008, 10, 537; e) V. H.
Gessner, S. Dilsky, C. Strohmann, Chem. Commun. 2010, 46, 4719; f) S.
Roesner, J. M. Casatejada, T. G. Elford, R. P. Sonawane, V. K. Aggarwal,
Org. Lett. 2011, 13, 5740; g) J. Lefranc, A. M. Fournier, G. Mingat, S. Her-
bert, T. Marcelli, J. Clayden, J. Am. Chem. Soc. 2012, 134, 7286; h) K. N.
Baryal, D. Zhu, X. Li, J. Zhu, Angew. Chem. Int. Ed. 2013, 52, 8012;
[18] R. Appel, Angew. Chem. Int. Ed. Engl. 1975, 14, 801; Angew. Chem. 1975,
87, 863.
[19] The other diastereomer was prepared to estimate the diastereomeric
ratio. (See Supporting Information).
Received: April 24, 2016
Published online on && &&, 0000
&
&
Chem. Eur. J. 2016, 22, 1 – 5
www.chemeurj.org
4
ꢀ 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
ÝÝ These are not the final page numbers!

Communication
COMMUNICATION
&
Lithium Reagents
V. Morozova, K. Moriya, P. Mayer,
P. Knochel*
&& – &&
Stereoselective Synthesis and
Retentive Trapping of a-Chiral
Secondary Alkyllithiums Leading to
Stereodefined a,b-Dimethyl Carboxylic
Esters
Lithium is the star: An I–Li-exchange
allows a highly stereoretentive prepara-
tion of a range of a-chiral secondary al-
kyllithium reagents, which, after
quenching with ClCO2Et, provide both
anti- and syn-ester carboxylates bearing
two or three adjacent stereocenters.
Chem. Eur. J. 2016, 22, 1 – 5
www.chemeurj.org
5
ꢀ 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
&
&
These are not the final page numbers! ÞÞ