Oxidative fragmentation of bicyclic hydroxy silanes and stannanes: a strategy for the stereoselective synthesis of kainoids

The addition of tin or silicon nucleophiles to bicyclic enones generated by dearomatising cyclisation gives stannanes and silanes stereoselectively. These compounds may be fragmented under oxidative conditions to generate substituted pyrrolidines bearing C2 and C3 substituents closely related to those found in the kainoid series of cyclic amino acids.     

Allylsilyl Propargyl Ethers as Substrates for Intramolecular Pauson–Khand Reactions

Silyl ethers that are synthesized by coupling a propargylic alcohol with an allylsilyl chloride are shown to undergo sulfide‐promoted Pauson–Khand reactions, affording bicyclic enones.     

Improved Synthesis of Cyclic Tertiary Allylic Alcohols by Asymmetric 1,2‐Addition of AlMe3 to Enones

The development of an improved protocol for the enantioselective Rh^I/binap‐catalysed 1,2‐addition of AlMe₃ to cyclic enones is reported. ³¹P NMR analysis of the reaction revealed that the catalyst in its resting state is a chloride‐bridged dimer. This insight led to the use of AgBF₄ as an additive for in situ activation of the dimeric precatalyst. Thus, the catalyst loading can now be reduced to only 1 mol % with respect to rhodium. Various 5–7‐membered cyclic enones can be transformed into tertiary allylic alcohols with excellent levels of enantioselectivity and high yields. The obtained products are versatile synthetic building blocks, shown by a highly enantioselective formal total synthesis of the pheromone (?)‐frontalin as well as formation of a bicyclic lactone that has the core structure of the natural flavour component “wine lactone”.     

Stereoselective Construction of Halogenated Quaternary Carbon Centers by Brønsted Base Catalyzed [4+2] Cycloaddition of α‐Haloaldehydes

Asymmetric construction of halogenated quaternary carbon centers under mild reaction conditions remains challenging. Reported here is an unprecedented and highly stereoselective Brønsted base catalyzed [4+2] cycloaddition between either α‐chloro‐ or α‐bromoaldehydes and cyclic enones. The key intermediate, an α‐halogenated enolate, is susceptible to dehalogenation and can be stabilized and stereochemically controlled using bifunctional tertiary amines. This method provides facile access to a collection of optically pure bicyclic dihydropyrans having three contiguous stereocenters, including a halogen‐bearing quaternary carbon center. Of note, the product can be transformed in situ into densely functionalized spirocyclopropanes in a highly efficient and stereoselective manner.     

Highly anti-selective SN2' substitutions of chiral cyclic 2-iodo-allylic alcohol derivatives with mixed zinc-copper reagents

[reaction: see text] Functionalized allylic electrophilic reagents such as chiral 2-iodo-1-cyclohexenyl and -cyclopentenyl phosphates undergo highly stereoselective anti-S(N)2'-allylic substitution reactions with a wide range of organozinc reagents (R(2)Zn and RZnI) leading to chiral products with a transfer of the chiral information >95%. The use of functionalized organozinc iodides allows preparation of the bicyclic enones 8 and 9 in >or=93% ee.     

Asymmetric Inverse-Electron-Demand Hetero-Diels–Alder Reaction for the Construction of Bicyclic Skeletons with Multiple Stereocenters by Using a Bifunctional Organocatalytic Strategy: An Efficient Approach to Chiral Macrolides

We have performed the first bifunctional organocatalytic highly enantioselective inverse-electron-demand hetero-Diels–Alder reaction of cyclic ketones with enones to afford densely functionalized bicyclic skeletons that contain three stereocenters (up 82 % yield, 10:1 d.r., and 97 % ee). Unlike the previous IEDDAR catalytic strategy, this method features a double HOMO_dienophile/ LUMO_diene-activated pathway. Moreover, this process provides a promising method for the construction of enantioenriched macrolides.     

α-Carbonyl Radicals for Total Synthesis of Natural Products

Intramolecular cyclization of α-carbonyl radicals to the trimethylsilylacetylenic side chain gives bicyclic vinylsilane ketones and enones. Application of this cyclization to total synthesis of (±)-modhephene is described.     

Asymmetric inverse-electron-demand hetero-diels-alder reaction for the construction of bicyclic skeletons with multiple stereocenters by using a bifunctional organocatalytic strategy: an efficient approach to chiral macrolides

We have performed the first bifunctional organocatalytic highly enantioselective inverse-electron-demand hetero-Diels-Alder reaction of cyclic ketones with enones to afford densely functionalized bicyclic skeletons that contain three stereocenters (up 82?% yield, 10:1 d.r., and 97?% ee). Unlike the previous IEDDAR catalytic strategy, this method features a double HOMO(dienophile) / LUMO(diene) -activated pathway. Moreover, this process provides a promising method for the construction of enantioenriched macrolides.     

Diels-Alder Approach to Highly Functionalized Tertiary α-Hydroxy Ketones: A Novel Route to the Hexahydrobenzofuran Portion of the Avermectins and Milbemycins

A highly regio- and stereoselective Diels-Alder reaction between dienophiles of type I and dienes of type II (Scheme 1) gives rise to Diels-Alder adducts of type III . Upon treatment with BF₃.Et₂O, these adducts are smoothly converted into the corresponding enones (Scheme 6). Under mild acidic conditions, enone (±)- 33 gave bicyclic diketone (±)- 34 via an intramolecular Michael-type addition. Diketone (±)- 34 has the correct relative configuration and a suitable ketone function at C(6) for further conversion into the hexahydrobenzofuran portion of the avermectins and milbemycins.     

Sur une possibilite d'acces aux cetones macrocycliques par les ene-allenes

Ene-allenes can be valuable precursors for the obtention of bicyclic enones, key-intermediates for the synthesis of macrocyclic ketones like exaltone and muscone.     

Spectral effects in cyclobutane derivatives : The bathochromic-hypochromic shifts in compounds related to verbenone

The bathochromic-hypochromic spectral shifts, observed in bicyclic enones that contain a 4- or a 3-membered ring, are discussed in molecular-mechanical and molecular-orbital terms. It is proposed that the effect, not only by the cyclopropane but also by the cyclobutane ring, is due to extension of the CCCO chromophore, and not to its mere distortion from “normal” geometry. The high-energy absorption of umbellulone (3), 220 nm in ethanol, is characterized as a second π-π^*. 2-Methylbicyclo[3.2.1]oct-2-en-4-one (7) has been synthesized, and its preparation and spectrum are described.     

Sequential actions of palladium and cobalt nanoparticles immobilized on silica: one-pot synthesis of bicyclic enones by catalytic allylic alkylation and Pauson-Khand reaction

[reaction: see text] Palladium and cobalt nanoparticles immobilized on silica have been used as catalyst in a sequential allylic alkylation and Pauson-Khand reaction to form bicyclic enones.     

A new strategy for construction of angularly fused tricyclic ring systems. Transannular bond formation of bicyclic enones via photochemical intramolecular hydrogen abstraction

Tricyclic ketones 3a, b and 7a–c having angularly fused 5-6-5 or 5-7-5 ring system have been efficiently prepared by irradiation of bicyclic enones 1 and 2.     

On the scope of diastereoselective epoxidation of various chiral auxiliaries derived enones: the conformational analysis of camphor derived N- and O-enones

Various camphor derived N- and O-enones were treated with selected oxidants to provide the corresponding epoxides in a wide range of diastereoselectivity. For camphorsultam derived activated alkenes, high to excellent stereoselectivities were obtained when the s-trans enones were treated with methyl(trifluoromethyl)dioxirane. On the other hand, for exo-10,10-diphenyl-2,10-camphanediol (3) and exo-10,10-diphenyl-10-methoxy-2-camphanol (4) derived alkenes, the use of s-cis enones gave the desired epoxide with excellent diastereoselectivity under the same reaction conditions. The stereoselectivity was highly dependent on the geometry of the auxiliaries derived enones and the stereochemical induction is discussed.     

Synthesis of cis-6,6,9-trimethyl-Δ3,4-octalin-2-one and cis-6,9-dimethyl-6-carbomethoxy-Δ3,4-octalin-2-one : Potential de synthons for the construction of pentacyclic triterpenes

Synthesis of the bicyclic enones (1 and 2) which are precursors for the rings DE of the pentacyclic triterpenes, β-amyrin and glycyrrhetinic acid has been reported from the readily available 6 - methoxy - 2- naphthoic acid.     

Synthèses stéréosélectives des γ-lactones bicycliques condensées

A highly stereoselective synthesis of trans/trans and cis/trans bicyclic γ-lactones is described using bicyclic dicarboxylic anhydrides.     

Highly Diastereoselective Reduction of Bicyclic and Steroidal Conjugated Enones with Dibal in THF-DME

Reduction of four bicyclic and two steroidal conjugated enones employing diisobutylaluminum hydride (DIBAL) in tetrahydrofuran (THF)/1,2-dimethoxyethane (DME) led to allylic alcohols with high levels of diastereo-selectivity.     

Zur Darstellung von Enonen aus 1-(3,3-Dimethyl-2-norbornyl)-ethanon

The synthesis of ,-unsaturated ketones via the regiospecific aldol reaction of the title ketone with some aldehydes is described and their properties and spectra discussed. Theexo-configuration at C-2 is retained in the bicyclic enones. The camphoraceous odour of the starting ketone is replaced by a floral-fruity odour of the enones.     

底物与条件控制苯胺与丙烯醛/烯酮的化学选择性偶联反应（英文）

金属催化碳氢键活化已经成为制备高附加值有机化合物的一类高效方法,由于碳氢键广泛存在,所以对它们进行化学、区域、立体选择性的活化作为一大挑战已经被人们日益所关注,然而氧化还原选择性控制的研究十分少见.通常而言,有机氧化还原反应定义为得失氢氧原子,例如消除氢负离子为氧化反应,而失去一个质子则为中性反应.在已有的研究中单独的氧化、还原反应已经被广泛研究,而且被大量用于医药合成、精细化工品的制备以及各类先进材料的生成.但是在同一反应体系下同时调控三种氧化态的研究目前未见报道,因此发展这类选择性控制的反应十分重要.我们此前已经实现了Rh(Ⅲ)/Ir(Ⅲ)催化苯胺和烯酮还原偶联合成四氢喹啉和高烯丙基苯胺两种产物,同时也能得到中性的1,2-二氢喹啉产物.在此工作的基础上,我们希望能够进一步实现相同反应组分的氧化偶联.为此,我们仔细分析取代的苯胺与烯酮的可能反应路径,发现可能的关键物种G—含有Rh(Ⅲ)的六元杂环中间体有望实现这类氧化过程,当用丙烯醛做底物时,物种G有可能实现円-氢消除得到氧化的二氢喹啉酮和Cp*RhXH,通常Cp*RhXH很容易发生自身的还原消除得到Cp*Rh(Ⅰ)使反应终止,但是,丙烯醛的存在有可能重新活化Cp*RhXH使得催化循环一直进行下去.另一种情况是中间体G发生质子解然后脱水得到亚胺物种,亚胺很容易被亲核试剂进攻得到中性的氮杂缩醛类产物.当然,外加银盐氧化剂还有可能得到另一种氧化型的喹啉盐.基于这种思路,我们发展了Rh(Ⅲ)-催化碳氢活化N-取代的苯胺与丙烯醛/烯酮的选择性偶联反应,反应可以化学选择性专一地制备三类不同的杂环化合物.当氮-吡啶基苯胺与丙烯醛反应时,反应类型为氧化过程,经历了转移氢化的过程,其中烯醛为主要的氢受体,得到二氢喹啉酮产物;如果定位基换成嘧啶时,在相似的反应条件下,反应类型为氧化还原中性过程,生成氮杂缩醛醚类产物;氮-吡啶基苯胺和烯酮反应在AgBF_4的氧化作用下同样可以发生氧化反应得到喹啉盐类化合物.至此,我们实现了导向基团对氧化反应和中性反应的控制,氧化剂的种类对反应路径的改变.反应的底物范围广泛,官能团容忍性好,我们期待这类氧化还原多样性的杂环合成方法能促进更多新颖反应的发现.     

Asymmetric cyclization-carbonylation of 2-propargyl-1,3-dione

The first example of asymmetric cyclization-carbonylation of 2-propargyl-1,3-dione 1 catalyzed by palladium(II) with chiral bisoxazolines (C.H.-BOX) was investigated. The use of bulky alcohols increased the ee of the products 2. The product 2d was converted into bicyclic enones 7 and 8, a useful intermediate for the synthesis of natural products.