Angewandte
Communications
Chemie
Ring Contraction
Stereospecific Construction of Contiguous Quaternary All-Carbon
Centers by Oxidative Ring Contraction
Xin Yu+, Jiadong Hu+, Zhigao Shen, Hui Zhang, Jin-Ming Gao, and Weiqing Xie*
Abstract: Oxidative ring contraction of cyclic a-formyl
ketones was facilitated by the action of H2O2 under operation-
ally simple and environmentally benign reaction conditions.
The process was highly regioselective and enables stereospe-
cific construction of contiguous quaternary all-carbon centers
from stereodefined all-substituted all-cyclic ketones. The
asymmetric syntheses of (+)-cuparene and (+)-tochuinyl
acetate were also successively achieved by taking advantage
of this novel protocol.
based on pericyclic, alkylation, photochemical, transition
metal catalyzed, and radical reactions,[5] most of them only
provide entry to specific scaffolds with one stereoisomer
being accessed. In consideration of collectively synthesizing
congeners of natural products with different contiguous
quaternary all-carbon centers, it remains highly desirable to
develop a general strategy which enables the stereospecific
construction of all stereoisomers of the framework.
In this respect, direct extrusion of carbonyl from all
substituted ketones under photoirradiation[6] is quite straight-
forward for forging contiguous quaternary all-carbon centers
because the stereoselective construction of all-substituted
ketones could be easily realized by enriched enolate chemis-
try.[7] However, this reaction is plagued by complicated
reaction pathways and lack of stereocontrol, both of which
lead to low yields. Recently, Garcia-Garibay and co-workers
uncovered that photoinduced decarboylation of all substi-
tuted ketones in the crystalline state quantitatively and
stereospecifically afforded compounds with contiguous qua-
ternary all-carbon centers (Figure 2a).[8] Unfortunately, this
T
he biological profiles of natural products mainly depend on
their three-dimensional shapes, which are usually influenced
by quaternary carbon centers if present. In this regard, natural
products incorporating contiguous quaternary all-carbon
centers are frequently isolated and possess unique structures.
Sometimes, both stereoisomers of contiguous quaternary all-
carbon centers are encountered in the same family of natural
products (Figure 1; e.g., communesin F[1] and perophorami-
dine,[2] and tochuinyl acetate[3] and herbertenolide[4]).
Figure 1. Natural products bearing both stereoisomers of contiguous
quaternary all-carbon centers.
Construction of contiguous quaternary all-carbon centers
constitutes a formidable challenge in natural products syn-
thesis because of the severe steric repulsion between the
substituents.[5] Although a variety of elegant strategies and
methodologies have been devoted to access to such motifs
Figure 2. Construction of contiguous quaternary centers via ring con-
traction of cyclic ketone.
[*] X. Yu,[+] J. Hu,[+] Prof. Dr. J.-M. Gao, Prof. Dr. W. Xie
Shaanxi Key Laboratory of Natural Products & Chemical Biology
School of Chemistry & Pharmacy, Northwest A&F University
22 Xinong Road, Yangling 712100, Shaanxi (China)
E-mail: xiewq@nwafu.edu.cn
protocol requires crystalline ketones. Additionally, one of the
substituents at the two a-carbon atoms must be a radical-
stabilizing functional group (e.g., aromatic ring, ester, cya-
nide) in view of the generation of the stable biradical
intermediate. Furthermore, the reaction needs ultraviolet
Z. Shen
Shanghai Institute of Organic Chemistry
Chinese Academy of Sciences, Shanghai 200032 (China)
X. Yu,[+] Prof. Dr. H. Zhang
Shanghai University, Shanghai 200444 (China)
[+] These authors contributed equally to this work.
À
irradiation to initiate homolytic C C bond cleavage.
In line with our recent work on oxidative deformylation
reactions,[9] we envisioned that the a-formyl cyclic ketone 3
could condense with H2O2 to generate the Criegee inter-
mediate 4, which would lead to the 1,2-dioxolane A by
Supporting information for this article can be found under:
Angew. Chem. Int. Ed. 2016, 55, 1 – 5
ꢀ 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
1
These are not the final page numbers!