TETRAHEDRON:
ASYMMETRY
Tetrahedron: Asymmetry 11 (2000) 4417–4427 Pergamon
Chiral nonracemic C
2
-symmetric biphenyls by
desymmetrization of 6,6,2,2-tetramethoxy-1,1-biphenyl
Giovanna Delogu,
a,
* Davide Fabbri,
a
Maria Antonietta Dettori,
a
Alessandra Forni
b,†
and
Gianluigi Casalone
b
a
Istituto CNR Applicazione delle Tecniche Chimiche Avanzate ai Problemi Agrobiologici , Via Vienna 2,
I -07100 Sassari, Italy
b
Centro del CNR per lo Studio delle Relazioni tra Struttura e Reattivita ` Chimica, Via Golgi 19,
I -20133 Milan, Italy
Received 5 October 2000; accepted 11 October 2000
Abstract
Regioselective bromination of the title biphenyl 1 at the 3 and 3 positions and simultaneous
desymmetrization of the biphenyl has been achieved. Metal–halide exchange at the 3,3 positions
facilitated the introduction of functional groups in good yield. Regioselective reduction was obtained by
using (CH
3
)
3
SiI, L-Selectride and HI according to the functional groups on the biphenyls. Resolution of
6,6,2,2-tetramethoxy-3,3-dimethyl-1,1-biphenyl 3 was achieved by its conversion to the corresponding
phosphorothioamidate diastereomers of the (S )-(-)--methylbenzylamine. The absolute configuration of
(M)-(+)-3 was confirmed by X-ray analysis of the corresponding diastereomer. © 2000 Elsevier Science
Ltd. All rights reserved.
1. Introduction
The ability of the biphenyl system in transmitting conformational information
1
has attracted
considerable interest around this structure which is used in ligands in catalysis
2
and, recently, in
the chemistry of biologically active compounds, as synthetic ionophores,
3
as artificial ion
channels which specifically recognize biomembranes
4
and in the molecular recognition of
disaccharides.
5
This has stimulated many research groups to investigate new synthetic
approaches to prepare enantiopure biphenyls with interesting features.
6
Because of the interesting proprieties of C
2
-symmetric hydroxylated biphenyls in the chemistry
of bioactive compounds
7
as well as in asymmetric catalysis,
8
we considered the possibility of
developing a new class of C
2
-symmetric heterosubstituted biphenols starting from 6,6,2,2-tetra-
* Corresponding author. E-mail: g.delogu@iatcapa.ss.cnr.it
†
Author to whom inquires concerning the X-ray structure analysis should be directed. E-mail: aforni@csrsrc.mi.cnr.it
0957-4166/00/$ - see front matter © 2000 Elsevier Science Ltd. All rights reserved.
PII:S0957-4166(00)00410-9