Dramatic change of regioselectivity in the addition of silylated organolithium reagents with oxazolidines induced by the presence of a titanium salt

Article abstract of DOI:10.1016/S0040-4039(00)00947-3

Diastereoselective reactions between oxazolidines and organolithium reagents afford β-amino alcohols having chiral vinyl and alkynylsilane moieties. A meaningful change of regioselectivity, from the α- to the γ-position, occurred when these reactions were

Full text of DOI:10.1016/S0040-4039(00)00947-3

Tetrahedron Letters 41 (2000) 6059±6062
Dramatic change of regioselectivity in the addition of silylated
organolithium reagents with oxazolidines induced by the
presence of a titanium salt
Claude Agami, Sebastien Comesse and Catherine Kadouri-Puchot*
Á Â Â
Laboratoire de Synthese Asymetrique (UMR 7611), Universite Pierre et Marie Curie, Case courrier 47,
4 place Jussieu, 75005 Paris, France
Received 27 April 2000; accepted 2 June 2000
Abstract
Diastereoselective reactions between oxazolidines and organolithium reagents a€ord b-amino alcohols
having chiral vinyl and alkynylsilane moieties. A meaningful change of regioselectivity, from the a- to the
g-position, occurred when these reactions were performed in the presence of titanium isopropoxide, since
allyl and allenylsilane derivatives were thus produced. # 2000 Elsevier Science Ltd. All rights reserved.
Much interest has been focused on the preparation of enantio-enriched organosilicon
compounds which are very useful reagents in organic synthesis.1 Most particularly, allyl and
vinylsilanes are widely used as intermediates in organic chemistry.2 On the other hand,
diastereoselective additions of organometallic reagents onto imines and oxazolidines are
well-documented.3,4 With a view to synthesizing new optically active b-amino alcohols5 having an
unsaturated silane function,6 we studied the attack of the allyl and propargyl silylated lithium
compounds onto oxazolidines 1a±c. Reactions with the organolithium reagents derived from
allyltrimethylsilane 27 9 and 1-(trimethylsilyl)propyn 310 a€orded functionalized b-amino
alcohols 4 and 5 possessing, respectively, a vinyl or an alkynyl moiety.11
Condensation of 2S-phenylglycinol and aldehydes gave oxazolidines 1a±c. The vinylsilane moiety
of the produced b-amino alcohol 4a±c showed an E-geometry (Scheme 1). The diastereoisomeric
ratios, determined by H NMR analysis of the crude mixture, and the yields are described in
Table 1.
1
A change of regioselectivity was observed when the above reactions were performed in the
presence of titanium isopropoxide.12 As shown on Scheme 2, allylsilane 6 (50% yield, >95/5 dr)
and allenylsilane 7 (78% yield, >95/5 dr) were, respectively, produced from oxazolidines 1b and
1a under these conditions.
* Corresponding author. Tel/fax: 33 1 44 27 26 20; e-mail: kadouri@ccr.jussieu.fr
0040-4039/00/$ - see front matter # 2000 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(00)00947-3

6060
Scheme 1. (a) CH2ˆCHCH2SiMe3 2, sec-BuLi (5 equiv.), TMEDA (5 equiv.); (b) CH3CꢀCSiMe3 3, sec-BuLi (5
equiv.), TMEDA (5 equiv.)
Table 1
Scheme 2. (a) 2, sec-BuLi (5 equiv.), TMEDA (5 equiv.), Ti(Oi-Pr)4 (5 equiv.); (b) 3, sec-BuLi (5 equiv.), TMEDA
(5 equiv.), Ti(Oi-Pr)4 (5 equiv.)
The absolute con®gurations of b-amino alcohols were determined from three sets of data: (i) X-ray
structures of allenyl derivative 7 and of oxazolidinone 8 derived from compound 6; (ii) desilylation
followed by hydrogenation of products 6 and 5b; and (iii) hydrogenation of compounds 4b and
5b. The compound 9 was thus obtained either from 6 or 5b; this correlation reveals an R absolute
con®guration for the created stereocenter in compound 5b. Hydrogenation of 4b or 5b a€ords the
same product, b-amino alcohol 10, disclosing, in this case too, an R absolute con®guration for the
stereocenter in 4b (Scheme 3).
a- versus g-Regioselectivity shifts in the nucleophilic reactivity of allyl and propargyl silylated
lithium reagents pertain to a very intricate ®eld. Many parameters govern this regioselectivity and

6061
Scheme 3. (a) (Cl3CO)2CO, NaOH 6N, CH2Cl2 90%; (b) n-Bu4NF, THF; (c) H2, Pd, abs. EtOH; 89 and 56% overall
from 5b and 6; 57 and 75% from 4b and 5b
the presence of added metallic salts (M) seems to favor a-attack: this fact has been clearly
observed when the electrophile (E) was an aldehyde (Scheme 4).13,14
Scheme 4.
Mechanistic studies are currently underway in order to rationalize these results: either an
open-chain model or a chelated one are to be considered.3a It seems clear, however, that the
observed change of regioselectivity must be ascribed to the nature of the organometallic species.
Most likely, allyl and allenyl lithium reagents are involved, in their ionic form,14,15 in the reaction
depicted in Scheme 1. Addition of Ti(Oi-Pr)4 transforms these species into covalent allyl and
propargyl titanium derivatives,16 thus accounting for the formation of compounds 6 and 7.
Actually, b-amino alcohols are valuable precursors in many enantioselective syntheses. The
present methodology is currently being further investigated in order to synthesize new optically
active b-amino alcohols and to use them as substrates in asymmetric synthesis.
Acknowledgements
We are grateful to Dr. J. Vaissermann and Dr. C. Guyard who performed the X-ray
crystallographic data and to S. Guesne for his assistance.
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6062
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stirred at ^78ꢁC for 15 min and then warmed to rt for 30 min. After this time, the mixture was cooled to ^78ꢁC and
a solution of oxazolidine (0.88 mmol) in THF (4 ml) was slowly added. After 30 min at ^78ꢁC, the mixture was
allowed to warm to 0ꢁC and was then hydrolyzed. The crude mixture was analyzed by H NMR and puri®ed by
1
chromatography on silica gel (petroleum ether:ethyl acetate, 85:15) to a€ord the b-amino alcohols 4a±c.
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organolithium reagent mixture and this solution was stirred for 1 h before the addition of the oxazolidine.
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