Asymmetric ortho-lithiation of 1,n-dioxa[n]paracyclophane derivatives for the generation of planar chirality

Kazumasa Kanda; Risa Hamanaka; Kohei Endo; Takanori Shibata

doi:10.1016/j.tet.2011.12.031

Asymmetric ortho-lithiation of 1,n-dioxa[n]paracyclophane derivatives for the generation of planar chirality

Kazumasa Kanda, Risa Hamanaka, Kohei Endo, Takanori Shibata^*

^*Corresponding author for this work

School of Advanced Science and Engineering

Research output: Contribution to journal › Article › peer-review

27 Citations (Scopus)

Abstract

The asymmetric induction of planar chirality in 1,n-dioxa[n]paracyclophane derivatives via asymmetric ortho-lithiation is described. Enantioselective ortho-lithiation of unflippable 1,n-dioxa[n]paracyclophanes (n≤11) using sec-BuLi-(-)-sparteine at -78 °C and subsequent treatment with electrophiles gave the corresponding planar-chiral monosubstituted paracyclophanes with excellent ee. Further lithiation of these compounds and treatment with electrophiles gave planar-chiral paracyclophanes with two different substituents. Dilithiation of unflippable 1,n-dioxa[n]paracyclophanes gave the corresponding C ₂-symmetrical disubstituted products with almost perfect ee. In the case of flippable 1,n-dioxa[n]paracyclophanes (n≥12), a stepwise reaction was required for the highly enantioselective formation of disubstituted products.

Original language	English
Pages (from-to)	1407-1416
Number of pages	10
Journal	Tetrahedron
Volume	68
Issue number	5
DOIs	https://doi.org/10.1016/j.tet.2011.12.031
Publication status	Published - 2012 Feb 4

Keywords

Enantioselective
Paracyclophane
Planar chirality
ortho-Lithiation

ASJC Scopus subject areas

Biochemistry
Drug Discovery
Organic Chemistry

Access to Document

10.1016/j.tet.2011.12.031

Cite this

@article{7b189b91e34d436e90e6166e2641f3f1,

title = "Asymmetric ortho-lithiation of 1,n-dioxa[n]paracyclophane derivatives for the generation of planar chirality",

abstract = "The asymmetric induction of planar chirality in 1,n-dioxa[n]paracyclophane derivatives via asymmetric ortho-lithiation is described. Enantioselective ortho-lithiation of unflippable 1,n-dioxa[n]paracyclophanes (n≤11) using sec-BuLi-(-)-sparteine at -78 °C and subsequent treatment with electrophiles gave the corresponding planar-chiral monosubstituted paracyclophanes with excellent ee. Further lithiation of these compounds and treatment with electrophiles gave planar-chiral paracyclophanes with two different substituents. Dilithiation of unflippable 1,n-dioxa[n]paracyclophanes gave the corresponding C 2-symmetrical disubstituted products with almost perfect ee. In the case of flippable 1,n-dioxa[n]paracyclophanes (n≥12), a stepwise reaction was required for the highly enantioselective formation of disubstituted products.",

keywords = "Enantioselective, Paracyclophane, Planar chirality, ortho-Lithiation",

author = "Kazumasa Kanda and Risa Hamanaka and Kohei Endo and Takanori Shibata",

note = "Funding Information: K.K. is grateful to the Japan Society for the Promotion of Science for the fellowship support. This work was supported by Grant-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology, Japan (No. 23655091 ). We also thank Asahi Glass Foundation and the Global COE program {\textquoteleft}Center for Practice Chemical Wisdom{\textquoteright} by MEXT. We also thank Ms. T. Koike (Waseda Univ.) for her experimental assistance in the preliminary work.",

year = "2012",

month = feb,

day = "4",

doi = "10.1016/j.tet.2011.12.031",

language = "English",

volume = "68",

pages = "1407--1416",

journal = "Tetrahedron",

issn = "0040-4020",

publisher = "Elsevier Limited",

number = "5",

}

TY - JOUR

T1 - Asymmetric ortho-lithiation of 1,n-dioxa[n]paracyclophane derivatives for the generation of planar chirality

AU - Kanda, Kazumasa

AU - Hamanaka, Risa

AU - Endo, Kohei

AU - Shibata, Takanori

N1 - Funding Information: K.K. is grateful to the Japan Society for the Promotion of Science for the fellowship support. This work was supported by Grant-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology, Japan (No. 23655091 ). We also thank Asahi Glass Foundation and the Global COE program ‘Center for Practice Chemical Wisdom’ by MEXT. We also thank Ms. T. Koike (Waseda Univ.) for her experimental assistance in the preliminary work.

PY - 2012/2/4

Y1 - 2012/2/4

N2 - The asymmetric induction of planar chirality in 1,n-dioxa[n]paracyclophane derivatives via asymmetric ortho-lithiation is described. Enantioselective ortho-lithiation of unflippable 1,n-dioxa[n]paracyclophanes (n≤11) using sec-BuLi-(-)-sparteine at -78 °C and subsequent treatment with electrophiles gave the corresponding planar-chiral monosubstituted paracyclophanes with excellent ee. Further lithiation of these compounds and treatment with electrophiles gave planar-chiral paracyclophanes with two different substituents. Dilithiation of unflippable 1,n-dioxa[n]paracyclophanes gave the corresponding C 2-symmetrical disubstituted products with almost perfect ee. In the case of flippable 1,n-dioxa[n]paracyclophanes (n≥12), a stepwise reaction was required for the highly enantioselective formation of disubstituted products.

AB - The asymmetric induction of planar chirality in 1,n-dioxa[n]paracyclophane derivatives via asymmetric ortho-lithiation is described. Enantioselective ortho-lithiation of unflippable 1,n-dioxa[n]paracyclophanes (n≤11) using sec-BuLi-(-)-sparteine at -78 °C and subsequent treatment with electrophiles gave the corresponding planar-chiral monosubstituted paracyclophanes with excellent ee. Further lithiation of these compounds and treatment with electrophiles gave planar-chiral paracyclophanes with two different substituents. Dilithiation of unflippable 1,n-dioxa[n]paracyclophanes gave the corresponding C 2-symmetrical disubstituted products with almost perfect ee. In the case of flippable 1,n-dioxa[n]paracyclophanes (n≥12), a stepwise reaction was required for the highly enantioselective formation of disubstituted products.

KW - Enantioselective

KW - Paracyclophane

KW - Planar chirality

KW - ortho-Lithiation

UR - http://www.scopus.com/inward/record.url?scp=84855601605&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84855601605&partnerID=8YFLogxK

U2 - 10.1016/j.tet.2011.12.031

DO - 10.1016/j.tet.2011.12.031

M3 - Article

AN - SCOPUS:84855601605

SN - 0040-4020

VL - 68

SP - 1407

EP - 1416

JO - Tetrahedron

JF - Tetrahedron

IS - 5

ER -

Asymmetric ortho-lithiation of 1,n-dioxa[n]paracyclophane derivatives for the generation of planar chirality

Abstract

Keywords

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Cite this