Enantioselective synthesis of spirocyclic cyclopentenes: asymmetric [3+2] annulation of 2-arylideneindane-1,3-diones with MBH carbonates derivatives catalyzed by multifunctional thiourea–phosphines

doi:10.1016/j.tet.2012.07.013

Tetrahedron

Volume 68, Issue 38, 23 September 2012, Pages 7911-7919

https://doi.org/10.1016/j.tet.2012.07.013 Get rights and content

Abstract

The [3+2] annulation reactions of 2-arylideneindane-1,3-diones with Morita–Baylis–Hillman (MBH) carbonates proceeded smoothly in the presence of multifunctional thiourea–phosphines to produce the corresponding quaternary carbon centered spirocyclic cyclopentenes in moderate yields, with high diastereoselectivities and enantioselectivities under mild conditions. The plausible reaction has been also discussed on the basis of previous literature.

Graphical abstract

Multifunctional thiourea–phosphine TP3 is a fairly effective catalyst for the enantioselective synthesis of spirocyclic cyclopentenes via asymmetric [3+2] annulation of 2-arylideneindane-1,3-diones with MBH carbonates. The corresponding quaternary carbon centered spirocyclic cyclopentenes were obtained in moderate yields, with high diastereoselectivities and enantioselectivities under mild conditions.

Introduction

1,3-Indanedione and its derivatives constitute a unique group of compounds and attracted much attention of organic chemists and biologists due to their characteristic features.¹ Thus far, they have been widely employed in the synthesis of drugs,² in forensic chemistry for fingerprint detection,³ in dyes and pigments,⁴ and in semi- and photo-semiconductors,⁵ proving that 1,3-indanedione and its derivatives are versatile starting materials for the synthesis of potentially important compounds.

Mortia−Baylis−Hillman (MBH) adducts have been also proven to be suitable precursors for the synthesis of multifunctional cyclic compounds, because the in situ generated phosphorus ylides from MBH carbonates in the presence of tertiary phosphines are very reactive 1,3-dipoles in a variety of annulations.⁶ In this field, Lu and his co-workers first reported a series of intra- and intermolecular [3+n] annulations (n=2, 4, 6) using MBH carbonates as 1,3-dipoles with various electron-deficient olefins catalyzed by a tertiary phosphine, affording the corresponding cycloadducts in good yields and high regioselectivities under mild conditions.⁷ More recently, Zhang, Huang and He as well as their co-workers have also developed several MBH adducts involved in [4+1] annulations to give the cycloaddition products in high yields, respectively.⁸

To the best of our knowledge, there are few reports about asymmetric version of this reaction. The first report on the asymmetric intermolecular [3+2] cycloaddition of MBH carbonates with methyleneindolinones was disclosed by Barbas and his co-workers, providing the corresponding spirocyclopentane–oxindoles in good yields and high ee values.⁹ Then, Lu's group developed l-threonine-derived chiral phosphines and indicated that these chiral catalysts were effective promoters in the asymmetric [3+2] annulation of MBH carbonates with isatylidenemalononitriles to deliver the optically active cyclic products in high yields with high enantioselectivities.¹⁰ With regard to the intramolecular [3+2] annulation of MBH carbonates with electron-deficient olefins, Tang and his co-workers first utilized spirobiindane-based chiral phosphines as catalysts to produce the corresponding intramolecular [3+2] cyclic adducts in good yields along with high ee values.¹¹ Moreover, our group has designed and synthesized a series of chiral multifunctional thiourea–phosphine catalysts derived from an axially chiral binaphthyl scaffold and has also demonstrated that these chiral phosphines were very effective catalysts in the asymmetric aza-MBH reaction and asymmetric allylic substitution of MBH adducts, giving the corresponding products in good yields and excellent enantioselectivities as well as in the asymmetric [3+2] annulations of MBH carbonates with isatylidenemalononitriles, giving the desired cycloadducts in good yields along with moderate enantioselectivities.12, 13, 14 Recently, we have further developed a series of multifunctional thiourea–phosphine catalysts derived from natural amino acid and applied them in asymmetric [3+2] annulation of MBH carbonates with trifluoroethylidenemalonates to give corresponding highly functionalized trifluoromethyl or pentafluoroethyl-bearing cyclopentenes in excellent yields (upto >99%), high diastereoselectivities (upto 99:1) and enantioselectivities (upto 96%) under mild conditions.¹⁵ Herein as a part of our continuing interest in asymmetric annulation catalyzed by multifunctional thiourea–phosphines, we wish to report the asymmetric annulation of 2-arylideneindane-1,3-diones 1 with MBH carbonates 2 catalyzed by multifunctional thiourea–phosphines to afford the corresponding quaternary carbon centered spirocyclic cyclopentenes in moderate yields, high diastereoselectivities, and enantioselectivities under mild conditions.¹⁶

Section snippets

Results and discussion

Initially, we examined the reaction of 2-(4-nitrobenzylidene)indan-1,3-dione 1a (0.1 mmol, 1.0 equiv) with MBH carbonate 2a (0.2 mmol, 2.0 equiv) catalyzed by PPh₃ in THF (2 mL) at room temperature, the C-1 addition product 3a was obtained in 74% yield along with excellent diastereoselectivities (upto >99% dr) within 24 h. Based on the preliminary investigation on [3+2] annulation of 2-(4-nitro-benzylidene)-indan-1,3-dione 1a with MBH carbonate 2a, asymmetric version of this reaction was

General remarks

Melting points were determined on a digital melting point apparatus and temperatures were uncorrected. Optical rotations were determined at 589 nm (sodium D line) by using a Perkin–Elmer-341 MC digital polarimeter; [α]_D-values are given in unit of 10 deg⁻¹ cm² g⁻¹ ¹H NMR spectra were recorded on a Varian Mercury-300 and 400 spectrometer for solution in CDCl₃ with tetramethylsilane (TMS) as an internal standard; coupling constants J are given in Hertz. ¹³C NMR spectra were recorded on a Varian

Acknowledgements

We thank the Shanghai Municipal Committee of Science and Technology (11JC1402600), National Basic Research Program of China (973)-2010CB833302, the Fundamental Research Funds for the Central Universities and the National Natural Science Foundation of China for financial support (21072206, 20872162, 20672127, 20732008, 21121062, and 20702013).

References and notes (17)

F.-R. Zhong et al.
Angew. Chem., Int. Ed.
(2011)
Dubers, G. Progress in Medicinal Chemistry, vol. 10, p...
D. Leblois et al.
Eur. J. Med. Chem.
(1987)
D.B. Hansen et al.
Chem. Soc. Rev.
(2005)
K. Bello et al.
J. Chem. Soc., Perkin Trans. 2
(1987)
M.R. Bryce et al.
J. Chem. Soc., Perkin Trans. 2
(1989)
For selected references on the asymmetric reactions of MBH...C.-W. Cho et al.
Org. Lett.
(2004)
C.-W. Cho et al.
Angew. Chem., Int. Ed.
(2004)
B.M. Trost et al.
J. Am. Chem. Soc.
(2005)
Y.-S. Du et al.
Tetrahedron Lett.
(2004)
D.J.V.C. van Steenis et al.
Adv. Synth. Catal.
(2007)
Y.-Q. Jiang et al.
J. Am. Chem. Soc.
(2008)
H.-L. Cui et al.
Angew. Chem., Int. Ed.
(2009)
K. Jiang et al.
Chem. Commun.
(2009)
J. Peng et al.
Org. Lett.
(2010)
W.-S. Sun et al.
Org. Lett.
(2010)
T. Furukawa et al.
Org. Lett.
(2011)
T. Furukawa et al.
Angew. Chem., Int. Ed.
(2011)
Y.-S. Du et al.
Angew. Chem., Int. Ed.
(2003)
Y.-S. Du et al.
Org. Lett.
(2005)
J.-Q. Feng et al.
Tetrahedron
(2007)
S.-Q. Zheng et al.
Org. Lett.
(2008)
S.-Q. Zheng et al.
Tetrahedron Lett.
(2009)
S.-Q. Zheng et al.
Org. Lett.
(2009)
L.-W. Ye et al.
Angew. Chem., Int. Ed.
(2007)
X. Han et al.
J. Org. Chem.
(2009)
R. Zhou et al.
Org. Lett.
(2011)
J. Peng et al.
Org. Lett.
(2011)

There are more references available in the full text version of this article.

Cited by (65)

Organocatalytic Regio- and Enantioselective [3 + 2]-Annulations of Ninhydrin-Derived Morita-Baylis-Hillman Carbonates with 3-Methyleneoxindoles
2022, Journal of Organic Chemistry
A type of Morita–Baylis–Hillman (MBH) carbonates has been developed from ninhydrin. These MBH carbonates have been successfully employed as 3C-synthons in the organocatalytic asymmetric [3 + 2]-annulations of the isatin-derived electron-deficient olefins, affording structurally diverse spirooxindoles in high yield with excellent stereoselectivity. In particular, the regioselectivity of MBH carbonates was controlled by the reaction partner, 3-methyleneoxindoles with carbonyl groups (R = ArCO), affording β-selective products and 3-methyleneoxindoles with ester groups (R = CO₂Me) furnishing γ-selective products. The representative scale-up reactions and transformation of product were examined. The reaction mechanism was expounded by control experiments.
Catalyst-free and atom-economical 1,3-dipolar cycloaddition of C,N-cyclic azomethine imines: Facile synthesis of isoquinoline-fused spirocycles
2022, Green Synthesis and Catalysis
A highly efficient and environmentally benign 1,3-dipolar cycloaddition of C,N-cyclic azomethine imines with 5-alkenyl thiazolones and 2-arylidenindane-1,3-diones is developed for the construction of congested quaternary spiro-carbon centers. All these transformations can be smoothly performed in ethanol at room temperature, providing a catalyst-free and atom-economical access to diversely substituted novel isoquinoline-fused spirocycles in almost quantitative yields with high diastereoselectivities. The promising anti-tumor activity of these structurally novel spirocyclic compounds is reported as well.
Allylic Phosphorus Ylides Directly Generated from Alcohols with Water as the only Byproduct
2019, Organic Letters
A novel strategy for the preparation of allylic phosphorus ylides directly from Morita–Baylis–Hillman (MBH) alcohols in an environmentally benign manner was developed. With the assistance of a calcium catalyst, the S_N2′ process between phosphines and allylic alcohols occurred smoothly, delivering allylic phosphorus salts and calcium-stabilized hydroxide ions. Then, in situ deprotonation gave the allylic phosphorus ylides with water as the only byproduct. Functionalized 1,3-diene moieties can be conveniently obtained by trapping the ylides through a Wittig olefination.
Enantioselective Construction of All-Carbon Quaternary Stereogenic Centers by Using Phosphine Catalysis
2017, Asian Journal of Organic Chemistry
The asymmetric construction of all‐carbon quaternary stereogenic centers represents one of the most‐challenging tasks in organic synthesis, and it has drawn continuous attention from the synthetic community. Asymmetric phosphine catalysis has progressed at an astonishingly rate over the past decade and it offers the efficient creation of a diverse range of structural architectures. In this Focus Review, synthetic methods based on phosphine catalysis for the enantioselective construction of all‐carbon quaternary stereogenic centers are highlighted.
Asymmetric Construction of Highly Functionalized Spirobarbiturate-Cyclopentenes through Chiral Phosphine-Catalyzed [3+2] Annulation of Morita–Baylis–Hillman Carbonates with Barbiturate-Derived Alkenes
2016, Advanced Synthesis and Catalysis
Advances in Annulation Reactions Initiated by Phosphorus Ylides Generated in situ
2016, European Journal of Organic Chemistry
Over the past two decades, the rapid development of nucleophilic phosphane catalysis has transported phosphorus ylide chemistry into an area beyond olefination. Phosphorus ylides generated in situ on nucleophilic addition of phosphanes to electrophilic unsaturated species, followed by some necessary proton-transfer steps, have effected many powerful annulation reactions to construct carbo- and heterocycles with multifarious molecular architectures under mild conditions from readily available starting materials. By judicious choice of the nucleophilic phosphanes, efficient ylide annulation reactions with good control over reaction selectivity can be achieved. In this microreview, recent advances in annulation reactions initiated by phosphorus ylides generated in situ are summarized according to the sources of the phosphorus ylides.

View all citing articles on Scopus

View full text

Enantioselective synthesis of spirocyclic cyclopentenes: asymmetric [3+2] annulation of 2-arylideneindane-1,3-diones with MBH carbonates derivatives catalyzed by multifunctional thiourea–phosphines

Abstract

Graphical abstract

Introduction

Section snippets

Results and discussion

General remarks

Acknowledgements

Angew. Chem., Int. Ed.

Eur. J. Med. Chem.

Chem. Soc. Rev.

J. Chem. Soc., Perkin Trans. 2

J. Chem. Soc., Perkin Trans. 2

Org. Lett.

Angew. Chem., Int. Ed.

J. Am. Chem. Soc.

Tetrahedron Lett.

Adv. Synth. Catal.

J. Am. Chem. Soc.

Angew. Chem., Int. Ed.

Chem. Commun.

Org. Lett.

Org. Lett.

Org. Lett.

Angew. Chem., Int. Ed.

Angew. Chem., Int. Ed.

Org. Lett.

Tetrahedron

Org. Lett.

Tetrahedron Lett.

Org. Lett.

Angew. Chem., Int. Ed.

J. Org. Chem.

Org. Lett.

Org. Lett.