Search

Access to chiral polysubstituted cyclobutanones by [2 + 2]-cycloaddition of ketenes with chiral acyclic enol ethers is reported. A wide variety of easily accessible di- and monosubstituted ketenes were found to react with a very high degree of stereoselectivity with chiral, Stericol derived, acyclic enol ethers. This combination of simple reagents provides straightforward entry to highly substituted enantioenriched cyclobutanones. more...

Ynol ethers are highly valuable substrates offering a wide range of reactivity. These highly electron-rich heterosubstitued alkynes can be of great synthetic potential. In this mini-review, the different methods for the synthesis of ynol ethers are first presented, divided in three main approaches involving a β-elimination, a carbene rearrangement and a direct oxidation of an alkyne. Their reactivity is then summarized underlying their synthetic utility. This non-exhaustive review aims at presenting the intrinsic reactivity of these compounds, still underexploited in synthesis. more...

The difluoromethyl phosphonate motif plays a crucial role in the development of bioactive molecules as it is considered as a phosphate bioisoster. Since 2010, a renewal of interest to enlarge the panel of reactions to access these difluoromethylated phosphonate-containing molecules has been witnessed. This Concept article charts the recent progress that has been made. more...

The OCF3 group is of high interest in the quest for new drugs and agrochemicals, thanks to its atypical features. This Highlight article depicts the recent and impressive advances toward the synthesis of OCF3-containing molecules. more...

A catalytic asymmetric synthesis of halocyclopropanes is described. The developed method is based on a carbenoid cyclopropanation of 2-haloalkenes with tert-butyl α-cyano-α-diazoacetate using a chiral rhodium catalyst that permits access to a broad range of highly functionalized chiral halocyclopropanes (F, Cl, Br, and I) in good yields, moderate diastereoselectivity, and excellent enantiomeric ratios. The reported methodology represents the first general catalytic enantioselective approach to halocyclopropanes. more...

Conspectus11-Nor PGE2 was prepared in our laboratory several years ago and used to obtain the corresponding ring-expanded γ-butyrolactam, γ-butyrolactone, and cyclopentanone derivatives. The conversion of a cyclobutanone into a cyclopentanone had relatively little precedent and merited further study. It was soon found that the presence of a single chlorine adjacent to the carbonyl not only greatly accelerated the reaction with ethereal diazomethane, but also substantially enhanced its regioselectivity; not surprisingly, a second chlorine further increased both.The confluence of this finding and the discovery by Krepski and Hassner that the presence of phosphorus oxychloride significantly improved the Zn-mediated dehalogenation procedure for the preparation of α,α-dichlorocyclobutanones from olefins provided the starting point for decades’ worth of exciting adventures in natural product synthesis. A wide variety of naturally occurring 5-membered carbocycles (e.g., hirsutanes, cuparenones, bakkanes, guaiano... more...

A general and efficient access to aryl, heteroaryl, vinyl and alkynyl difluoromethylphosphonates is described. The developed methodology using TMSCF2PO(OEt)2, iodonium salts and a copper salt provided a straightforward manifold to reach these highly relevant products. The reaction proved to be highly functional group tolerant and proceeded under mild conditions, giving the corresponding products in good to excellent yields. This method represents the first general synthetic route to this important class of fluorinated scaffolds, which are well-recognized as in vivo stable phosphate surrogates. more...

The reaction of furanose and pyranose derivatives with optically active sulfinamidine (II) gives the title compounds (III) and (VII), respectively.

Difluoromethylated arenes are scaffolds of great interest. We report herein a mild and general method for the introduction of the CF2PO(OEt)2 moiety into arenes. The CuCF2PO(OEt)2 species, which is generated in situ from the corresponding silylated derivatives, in combination with aryl diazonium salts furnished the highly valuable aryl difluoromethylphosphonates in moderate to good yields. This represents the first general method to introduce difluoromethylphosphonates under mild conditions. more...

An efficient access to highly functionalized monofluorocyclopropanes is described. The developed methodology allowed straightforward access to a large panel of polysubstituted fluorinated cyclopropanes in good to excellent yields and good diastereoselectivities. The Rh-catalyzed cyclopropanation proved to be efficient on several fluorinated olefins and several diazo compounds. This method represents the first general route to complex fluorinated cyclopropanes. more...

The procedure uses the high difference in reactivity and thus allows the access to pure (E) alkenes, often difficult or impossible to isolate from the mixtures or expensive in trade.

The first direct introduction of a functionalized fluorinated moiety into electron-rich arenes by a copper-catalyzed radical-free process is reported.

The direct vicinal difunctionalization of versatile alkynes is an area of considerable interest. In particular, the concomitant introduction of a functional group and a fluorinated moiety offers new efficient synthetic routes to the construction of highly functionalized olefins, key building blocks in the synthesis of several complex and relevant molecules. This review highlights the major progress that has been made in this field offering an overview of the direct concomitant introduction of a range of functional groups and various fluorinated moieties into alkynes through radical and metal-catalyzed processes. In addition, rearrangement reactions involving molecules containing alkynes and leading to fluorinated alkenes are also carefully depicted. more...

The alkynylcopper substrates are prepared as yellow solids and directly used in the reaction with the inexpensive ester (II) under mild conditions.

Review: [direct functionalization of alkenes and alkynes with fluorine or fluorinated building blocks using photocatalyzed transformations, base-promoted processes, and transition metal-catalyzed reactions; 58 ref. more...

Diazocarbonylated Cyclic N‐Hydroxylamines: A New Approach to Cyclic Ketonitrones” Evelyn Lieou Kui, Alice Kanazawa,* Jean-Francois Poisson, and Sandrine Py* Org. Lett. 2014, 16 (17), 4484−4487, DOI: 10.1021/ol502029z T authors retract this Letter because recently obtained Xray diffraction data reveals that the structures of the products reported and the reaction mechanism described are incorrect. more...

2-Deoxy-2-amino-substituted glycosides are ubiquitous compounds in biochemistry and biology. Therefore, the development of new synthetic pathways to access natural and non-natural derivatives is highly desirable. In that context, 2-nitroglycals appeared as versatile building blocks for reaching those targets. Since their first introduction almost forty years ago, their synthetic utility has been widely demonstrated and they have been used to access natural and non-natural compounds with potent biological activity. The aim of this review is to summarize the developed routes to these versatile intermediates as well as their reactivity. The main applications of the chemistry developed with 2-nitroglycal derivatives is also highlighted in this first review. more...

The highly diastereoselective addition of hetarenes to a chiral cyclic nitrone ((R)-II) followed by methanolysis, oxidation with Pb(OAC)4 and reaction with hydroxylamine produces a range of α-(hydroxylamino)esters in good yields and good enantioselectivities. more...

The nitro-Michael addition of organolithium species to 2-nitroglycal derivatives was investigated. This methodology affords straightforward and stereoselective access to C-nitroglycosides, which are excellent precursors to C–N-acetylglycosamines. The corresponding products bearing an aromatic, heteroaromatic, alkynyl, alkenyl, or alkyl moiety were isolated in good yields with excellent selectivities. The β isomer was isolated as a single stereoisomer in most cases, and the structure was clearly elucidated by NMR spectroscopy experiments. more...

The first example of a high facial selective [3 + 2] cycloaddition employing chiral vinyl ethers as dipolarophile and nitrones as dipoles is presented.

The first Cu-catalyzed selective difluoromethylation reaction of benzofurans and furans is presented.

A copper-mediated fluorofunctionalization of alkenes and alkynes has been developed. This method provides ready access to trisubstituted difluoromethylated olefins (from dihydropyrans, glycal derivatives, or terminal alkynes) or to tetrasubstituted olefins (from disubstituted alkynes). The products were obtained in good to high yields with acceptable E/Z selectivities. Finally, a first direct route to difluoromethylated alkynes is reported, albeit with low yields. more...

We report herein the first general access to fluorinated homoallylic amines by means of an addition of fluorinated organoindium reagent. The corresponding amines were obtained in good to excellent yield with excellent diastereoisomeric ratio. A plausible mechanism is proposed to explain the stereochemical outcome of the reaction based on the X-ray structure of the products. more...

The regioselective Cu-catalyzed radical free synthesis of β-difluoroester substituted enamides is described.

Herein, an efficient access to fluorinated homoallylic alcohol is reported. The fluorinated alcohols were obtained in good to excellent yield using indium and halo-fluorinated allylic derivatives. The developed methodology using γ-substituted halo-fluorinated allylic derivatives gave the corresponding α-substituted fluorinated homoallylic alcohol in good yields and good diastereoselectivities up to 86:14. more...

The Honda—Reformatsky reaction involving bromodifluoroacetate (II) is investigated with both sulfinylimines derived from aliphatic aldehydes as well as those derived from aldehydes bearing a chiral α-oxygenated substituent. more...

A highly selective N-sulfinylimidate aldolization has been developed under mildly basic conditions leading to diastereopure products of high synthetic potential. The innate reversibility of this aldolization was suppressed by the use of titanium as the Lewis acid. An application of this methodology via the synthesis of a potential neurotransmitter reuptake inhibitor is illustrated. more...

The addition of in situ generated alkoxyethynyl aluminum reagents (II) to sulfinylimines (III) affords alkoxypropargylamines (IV) in high yields and with significant higher diastereoselectivities compared to the reaction of the corresponding lithio acetylides. more...

A new method for the synthesis of fluorinated α-C-glycosides is described. The reactions between highly electrophilic radicals (fluorinated or unfluorinated) and a 2-benzyloxyglucal or galactal provide 2-keto-D-arabino- or 2-keto-D-lyxo-hexopyranosides through an addition/fragmentation process. Sodium borohydride mediated or Meerwein-Ponndorf-Verley (MPV) reduction of these compounds provides α-C-glycosides that feature appropriate anchoring groups for further synthetic elaboration. The presence of CF2 CO2 iPr or CF2 Br groups at the pseudo-anomeric position allows efficient reduction/olefination or Br/Li-exchange/nucleophilic-addition sequences. These transformations open the way for the synthesis of fluorinated C-glycosidic analogues of glycoconjugates. more...

A novel and efficient nucleophilic addition of metalated α-diazoacetates to a variety of nitrones is described. This approach provides a series of stable unprecedented β-alkylhydroxyamino-α-diazoesters with great synthetic potential. more...

A copper catalyzed direct functionalization of dihydropyrans and glycals has been developed. This method affords a new and straightforward access to C-2-CF2 dihydropyrans and glycosides in a single step starting from readily available starting materials. This new copper based catalytic system, probably involving a Cu(III) species as supported by experiments, allows the formation of the valuable fluorinated glycosides in good yields. more...

Depending on the nature of the amide, diethylzinc-mediated additions of 2,2-dibromo-2-fluoroacetamides to aldehydes, ketones or imine afford selective access either to bromofluorohydrins or to (Z)-α-fluoroacrylamides. more...

Indium-mediated reaction of the fluoropropene (II) with different types of aldehydes gives fluorinated homoallylic alcohols in a brine solution.

Aryloxypropargyl sulfinamides (III) are efficiently obtained, in most cases with high diastereoselectivity.

A convenient method for the copper(II)-catalyzed direct arylation of cyclic and nonaromatic enamides using diaryliodonium salts has been developed. The reaction demonstrates large functional group tolerance, good yields, and total regioselectivity with a C(3)-functionalization. The synthetic potential of this coupling was explored by using a range of readily accessible diaryliodonium salts and enamides. more...

The addition of boron trifluoride reverses completely the diastereoselectivity [cf.(III) versus (VII)].

The reaction of ortho-hydroxyphenones allows formation of fluorinated lactones such as (VII).

A simple and efficient method to prepare cis- and trans-disubstituted cyclobutanones is reported.

A transition metal-free Heck-type cyclization/isomerization reaction mediated by KOtBu and phenanthroline is described.

The visible light mediated photoredox transformation of tertiary amines (I) to azomethine ylides and subsequent cycloaddition with maleimide derivatives as dipolarophiles proceeds under mild conditions resulting in the simultaneous and diastereoselective formation of two C-C single bonds. more...

In the presence of Ph-CO-F/EtOH and (DHQ)2-AQN, silyl enol ethers smoothly undergo enantioselective protonation giving chiral ketones with up to 92% e.e..