❞ كتاب Synthesis of heterocycles by cyclization of unsaturated ❝

Synthesis of heterocycles by cyclization of unsaturated من كتب علمية

Synthesis of heterocycles by cyclization of unsaturated من كتب علمية 
Michael J. Mealy, William F. Bailey

Journal of Organometallic Chemistry 646 (2002) 59–67
www.elsevier.com/locate/jorganchem
Account
Synthesis of heterocycles by cyclization of unsaturated
organolithiums: a review
Michael J. Mealy, William F. Bailey *
Department of Chemistry, Uni
ersity of Connecticut, Storrs, CT 06269 -3060, USA
Received 9 July 2001; accepted 4 September 2001
Abstract
The preparation of oxygen and nitrogen containing heterocyclic compounds by cyclization of unsaturated organolithium
compounds has been reviewed. The review contains 57 references to relevant literature through early 2001. © 2002 Elsevier
Science B.V. All rights reserved.
Keywords: Intramolecular carbolithiation; Cyclization; Heterocycles; Organolithiums
1. Introduction
The preparation of heterocycles from acyclic precursors
constitutes one of the most studied areas of organic
chemistry, and over the past two decades,
significant advances have been made in the exploitation
of main group organometallics for this purpose. This
brief review serves to highlight the major achievements
in the development of anionic cyclization of olefinic
organolithiums as a synthetic tool for the preparation
of nitrogen- and oxygen-containing rings.
The 5-exo-trig cyclization of 5-hexenyllithiums [1]
has received a good deal of attention as a route to
cyclopentyl-containing systems and the preparation of
carbocycles via cyclization of unsaturated organolithiums
has been reviewed [2–4]. Surprisingly, the development
of this methodology for the efficient preparation
of heterocyclic systems has received less attention. It is
hoped that this survey will provide sufficient insight
into the nature of these species to stimulate further
growth in this area of main group chemistry.
2. Oxygen heterocycles
The first reports of carbolithiation of an unactivated
carbon–carbon double bond for the preparation of a
heterocycle appear to be two brief accounts in the early
1970s describing the intramolecular addition of -
oxyallyllithiums [5] and -oxybenzyllithiums [5,6] to the
carbon–carbon -bond of a norbornene. In 1980, Baldwin
and co-workers observed the novel rearrangement
of 1 to benzofuran 2 upon ortho-lithiation and, as
illustrated in Scheme 1, proposed a mechanism for the
transformation that involved intramolecular addition of
the aryllithium to the tethered -bond [7]. It should be
noted that the parent system, 2-(2-propenoxy)-
phenyllithium (3), rearranges upon warming in the
presence of TMEDA via 5-exo-cyclization to give 4,
however, as shown in Scheme 1, subsequent -elimination
affords the lithium salt of 2-cyclopropylphenol [8].
The first systematic studies of intramolecular carbolithiation
for the preparation of a heterocycle were
the seminal reports by Broka and co-workers detailing
the preparation of substituted tetrahydrofurans by anionic
cyclization of olefinic -alkoxyorganolithiums
[9,10]. These cyclizations were found to be highly
stereoselective as a consequence of the progression of
the isomerization through a rigid, chair-like transition
state analogous to that observed in the cyclization of
the parent 5-hexenyllithium [11,12