Molecules 2004, 9, 330-348
Masked ω-Lithio Ester Enolates: Synthetic Applications §
Miguel Yus,* Rosario Torregrosa and Isidro M. Pastor
Departamento de Química Orgánica, Facultad de Ciencias and Instituto de Síntesis Orgánica (ISO),
Universidad de Alicante, Apdo. 99, 03080 Alicante, Spain. Fax: (+34) 965 903549.
§ Dedicated to Professor Ramón Mestres on the occasion of his 65th birthday.
* Author to whom correspondence should be addressed; e-mail: email@example.com.
Received: 25 February 2004 / Accepted: 15 March 2004 / Published: 30 April 2004
Abstract: The protocol of lithiation by means of lithium and a catalytic (5% molar)
amount of DTBB (4,4’-di-tert-butylbiphenyl), applied to ω-chloro ortho ester 6 under
Barbier-type conditions gives, after final acid-catalyzed methanolysis, the corresponding
functionalized esters 8 or 9 (for chlorotrimethylsilane as electrophile) or, after ortho ester
deprotection and acid catalyzed treatment, the δ-lactones 11. The procedure is also
practical for bicyclic ortho esters 14: the β-chloro OBO ester derivate generates the γ-
lactones 15 and the γ-chloro OBO ester gives corresponding esters 8.
Keywords: Chlorine-lithium exchange; functionalized ester; arene-catalyzed lithiation.
Among organometallic reagents, organolithium compounds are the most reactive ones due to the
high ionic nature of the carbon-lithium bond . Functionalized organolithium compounds are very
useful in synthetic organic chemistry in order to transfer their functionality to electrophiles in a single
synthetic step, thus organolithium derivatives bearing a carboxylic moiety would transfer a carboxylic
group to an electrophilic reagent. The corresponding α-derivatives (carboxylate enolate, 1)  have
been prepared by double deprotonation [2,3] using lithium dialkylamides  as bases (e.g. LDA).
Recently, Parra et al.  have reported the generation of this intermediate (and the subsequent reaction