Quanrui Wang

Gold‐Catalyzed Cycloisomerization of Cyclopropyl Alkynyl Acetates: A Versatile Approach to 5‐, 6‐, and 7‐Membered Carbocycles

During the last decade, late-transition-metal-catalyzed cycloisomerizations have emerged as a powerful tool to access unprecedented structural and mechanistic diversity. In this context, a rapidly developing area involves the use of propargylic esters, preferably acetates, in which the carbonyl unit acts as a nucleophile onto the metal-activated alkyne complex I (Scheme 1). Two distinct mechanistic scenarios

Preparation of polymer-supported Ru-TsDPEN catalysts and use for enantioselective synthesis of (S)-fluoxetine

Polymer-supported chiral ligands 9 and 17 were prepared based on Noyoris (1S,2S)- or (1R,2R)-N-(p-tolylsulfonyl)-1,2-diphenylethylenediamine. The combination with [RuCl2(p-cymene)]2 has been shown to exhibit high activities and enantioselectivities for heterogeneous asymmetric transfer hydrogenation of aromatic ketones (19a-c) with formic acid-triethylamine azeotrope as the hydrogen donor, whereby affording the respective optically active alcohols 20a-c, the key precursors of chiral fluoxetine. As exemplified by ligand 17 for substrate 19c, the catalysts can be recovered and reused in three consecutive runs with no significant decline in enantioselectivity. The procedure avoids the plausible contamination of fluoxetine by the toxic transition metal species.

[3+2]-cycloadditions of 1-Aza-2-azoniaallene cations to multiple bonds

Abstract Hydrazones of ketones 1, are transformed into 1-chloroalkylazo compounds, 2, which react with Lewis acids to give transient 1-aza-2-azoniaallene salts, 3. The cations 3 react with with acetylenes, olefins, isocyanates, carbodiimides, and nitriles under [3+2]-cycloadditions. The cycloadducts undergo consecutive reactions, e.g. [1,2]-shifts of alkyl groups.

Efficient Macrocyclization by a Novel Oxy‐Oxonia‐Cope Reaction: Synthesis and Olfactory Properties of New Macrocyclic Musks

Musk odorants are indispensable in perfumery to lend sensuality to fine fragrances, a nourishing effect to cosmetics, and a comforting feeling to laundry. Due to a certain phototoxicity of nitro musks, and the lack of biodegradation of polycyclic musks, the two most important musk families at present are macrocycles 1–5 (Figure 1), derived from the natural lead muscone (1), and linear alicyclic musks such as 6–7, the odor of which has been attributed to horseshoeshaped conformers that mimic macrocyclic rings on the odorant receptors. Both musk families, linear as well as macrocyclic, comprise highly flexible structures, which make double bonds and methyl groups ideal design elements to rigidify and conformationally constrain them. The two most powerful macrocyclic musks, (+)-(3R,5Z)-5-muscenone (2) and (13R,10Z)-Nirvanolide (3) both feature a double bond and a methyl substituent, and Cosmone (4) can be regarded as a “nor-muscenone”. By introduction of two double bonds such as in 5, the conformational freedom can be further restricted, enabling a targeted design of potent musk odorants. Methyl substituents determine the conformational space of linear musks to a great extend; yet, as apparent from the two dehydro-derivatives 6 and 7 of Serenolide (Figure 1), a shift of a double bond can change the odor threshold by a factor of over 150. The synthesis of further unsaturated macrocyclic musks can shed light upon similarities in the structure–odor correlation of these two musk families, and to this purpose we herein report on the intramolecular application of a new reaction of b,g-unsaturated aldehydes with different aldehydes in the presence of Lewis acids. The projected macrocyclization can be regarded as an oxy-version of the established 2-oxonia Cope rearrangement, but as illustrated in Scheme 1, could as well proceed through compound 11 in a Prins-type manner by coordination of the Lewis acid to the opposite formyl function. Both pathways would however lead to the same macrocyclic alk-3-en-1-yl formates 10. Hydride reduction and subsequent oxidation of 10 should provide b,g-unsaturated macrocyclic ketones, which could then be hydrogenated to the saturated macrocycles; thus, could then also open up a new route to ( )-muscone (1). As delineated in Scheme 2, the dicarbonyl substrates 8 a–g were prepared from commercial bromo alcohols 12 a–g by protection as tert-butyldiphenylsilyl (TBDPS) ethers 13 a–g, and subsequent Finkelstein reaction with KI in acetone to afford iodides 14 a–g in excellent yields. Deconjugated a-alkylation of the Weinreb amide 15 with 14 a–g afforded alkylated amides 16 a–g in 39–60 % yield, with unreacted 14 a–g being recovered. Deprotection of the Weinreb amides 16 a–g with tetrabutylammonium fluoride (TBAF) in THF [a] Dr. Y. Zou, Prof. Dr. Q. Wang Department of Chemistry, Fudan University 220 Handan Road, Shanghai, 200433 (P.R. China) Fax: (+86) 216-564-1740 E-mail : qrwang@fudan.edu.cn [b] Dr. Y. Zou, Dr. A. Goeke Givaudan Fragrances (Shanghai) Ltd 298 Li Shi Zhen Road, Shanghai, 201203 (P.R. China) [c] Dr. H. Mouhib, Prof. Dr. W. Stahl RWTH Aachen University, 52056 Aachen (Germany) Institute of Physical Chemistry [d] Dr. P. Kraft Givaudan Schweiz AG, Fragrance Research berlandstrasse 138, 8600 D bendorf (Switzerland) Fax: (+41) 44-8242926 E-mail : philip.kraft@givaudan.com Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/chem.201200882. Figure 1. Macrocyclic musks 1–5, and linear musk structures 6 and 7.

Organocatalytic Multicomponent α-Methylenation/Diels-Alder Reactions : A Versatile Route to Substituted Cyclohexenecarbaldehyde Derivatives

This article describes the design and optimization of an effective organocatalytic three-component domino alpha-methylenation/Diels-Alder reaction to produce vinyl-substituted cyclohexenecarboxaldehydes in a highly regioselective fashion. In these one-pot transformations, 2-formyl-1,3-butadienes (4) were prepared in situ from alpha,beta-unsaturated aldehydes and formalin and were subsequently trapped with a variety of buta-1,3-dienes. The outcomes of the reactions were dependent on the electronic properties of the dienes. 1-Vinylcyclohexenecarbaldehydes 6 were formed by use of acyclic electron-rich dienes, while the initially formed cycloadducts of 4 with cyclopentadiene underwent Cope rearrangements, leading to the formation of tetrahydro-3H-indene-5-carbaldehyde compounds 7. The mechanisms involved in these reactions were deduced from experimental findings. Furthermore, the method was also extended to one-pot domino methylenation/Diels-Alder reactions of dihydrofurans and dihydropyrans to yield spirocyclic lactols 22. In these reactions, the unstable intermediate hydroxyethyl and hydroxypropyl acroleins behaved as dienophiles, undergoing cycloaddition reactions with dienes with good yields and selectivities. The wide variety of functionalized 1-vinylcyclohex-3-enecarbaldehydes 6, 4-vinylcyclohex-1-enecarbaldehydes 7, and spiro lactols 22 generated through the use of these organocatalytic domino processes as a diversity-oriented synthesis provided useful intermediates for the construction of novel odorants.

Unexpected Cycloisomerizations of Nonclassical Carbocation Intermediates in Gold(I)-Catalyzed Homo-Rautenstrauch Cyclizations

An unexpected gold(I)-catalyzed homo-Rautenstrauch rearrangement of 1-cyclopropyl propargylic esters to cyclohexenones is disclosed. This rearrangement represents new evidence for the recently discussed gold-stabilized nonclassical carbocation character of intermediates in gold catalysis. A mechanistic study proved partial chirality transfer from optically active propargyl acetates.

A facial synthesis of the neutral [1,2,4]triazolo-[3,2-d][1,5]benzoxazepines and their chalcogen-analogues

ABSTRACT An expedient synthesis of neutral [1,2,4]triazolo[3,2-d][1,5]-benzoxazepines 6a–e and their chalcogen analogues 6f–i was accomplished via cycloaddition of the heterocumulene cations (3a,b), generated sequentially by action of chroman-4-one as well as thiochroman-4-one ethoxy carbonylhydrazones (1a,b) with t-BuOCl and SbCl5, to the triple bond of nitriles and concurring ring enlargement and hydrolytic removal of the N(1)-ethoxycarbonyl group. The oily final products were characterized as their picrates.

Catalytic Asymmetric Prins Bicyclization for the endo-Selective Formation of 2,6-dioxabicyclo[2.2.2]octanes.

A new Lewis acid-catalyzed endo-selective Prins bicyclization of γ,δ-unsaturated aldehydes or ketones with a broad range of aldehydes to dioxabicyclo[2.2.2]octanes is disclosed. When using a chiral BINOL-derived N-triflylphosphoramide (NTPA) as catalyst and glyoxylate esters as substrates, the cross-dimerization afford functionalized bicyclic acetals with excellent diastereo- and enantioselectivities.

A novel oxy-oxonia(azonia)-cope reaction: serendipitous discovery and its application to the synthesis of macrocyclic musks.

This brief review, including new experimental results, is the summary of a talk at the GDCh conference ‘flavors & fragrances 2013’ in Leipzig, Germany, 11th–13th September, 2013. Musk odorants are indispensable in perfumery to lend sensuality to fine fragrances, a nourishing effect to cosmetics, and a comforting feeling to laundry. We have recently found serendipitously a new oxy‐oxonia‐Cope rearrangement. In this account, we review the background of oxonia‐sigmatropic rearrangements and the discovery of this novel reaction. Special attention is focused on the versatile lactone and lactam formation reactions via [n+4] ring enlargement and the macrocyclization in the synthesis of new macrocyclic musks. The synthesized structures provide new insights into the structureodor relationships of musks.

An Efficient Approach to the [1,2,4]-Triazolo[3,2-d][1,5]Benzoxazepine Skeleton-A Novel Tricyclic Ring System

Abstract Unprecedented [1,2,4]-Triazolo[3,2-d][1,5]benzoxazepine skeleton was easily achieved by cycloaddition of the allene-like cations 3, derived from 4-chromanone arylhydrazones, to the triple bond of nitriles and ensuing ring enlargement. The structural assignment of one product (5d) has been ultimately accomplished by X-ray diffraction analysis.