The palladium-catalyzed arylative dearomatization of phenols to yield spirocyclohexadienone products in good to excellent yields has been developed. Preliminary results demonstrate that the formation ...of the spirocyclic all-carbon quaternary center can be accomplished with high levels of enantiocontrol (up to 91% ee).
The ortho arylation of anilides to form biphenyls via a twofold C−H functionalization/C−C bond-forming process is described. The oxidative coupling takes place in the presence of 5−10 mol % of ...Pd(OAc)2, 10−20 mol % of DMSO, and 4−11 equiv of the aryl substrate in TFA under an oxygen atmosphere. No metal-containing cocatalyst is required.
An intramolecular enantioselective metal-catalyzed dearomatization reaction is described. This procedure allows the dearomatization of naphthalene derivatives through an electrophilic aromatic ...substitution-type reaction on a Pd(II) intermediate. The high yields and enantioselectivities achieved make this procedure a valuable method for synthetic chemists.
Despite increasing pharmaceutical importance, fluorinated aromatic organic molecules remain difficult to synthesize. Present methods require either harsh reaction conditions or highly specialized ...reagents, making the preparation of complex fluoroarenes challenging. Thus, the development of general methods for their preparation that overcome the limitations of those techniques currently in use is of great interest. We have prepared LPd(ll)Ar(F) complexes, where L is a biaryl monophosphine ligand and Ar is an aryl group, and identified conditions under which reductive elimination occurs to form an Ar-F bond. On the basis of these results, we have developed a catalytic process that converts aryl bromides and aryl triflates into the corresponding fluorinated arenes by using simple fluoride salts. We expect this method to allow the introduction of fluorine atoms into advanced, highly functionalized intermediates.
Phoxy ligand: The first catalytic method for the asymmetric palladium‐catalyzed intramolecular α‐arylation of α‐branched aldehydes was developed (see scheme). This process is distinguished by the ...high yields and enantioselectivities that can be obtained, making this protocol a useful synthetic tool for further applications.
We describe a concise and flexible synthetic avenue for the preparation of compounds with structures relevant to those proposed for the novel marine-derived differential cytotoxins psymberin and ...irciniastatin A. Our efforts led to their complete stereochemical assignment and the notion that psymberin and irciniastatin A are identical compounds. Our total synthesis features an interesting termini-differentiating lactolization of a dialdehyde obtained from a C 2-symmetrical bis-olefin precursor, a mild platinum-catalyzed hydrolysis of an epimerizable nitrile, a novel protocol to prepare sensitive methyl imidates, and a one-pot conversion of these imidates to N-acyl aminals. Starting from fragments 5−7 (prepared in 7−8 steps each, 30−49% overall yield) the synthesis of psymberin/irciniastatin A was completed in an additional 9 steps and 30% yield (17 steps longest linear sequence, 8.9% overall).
A stereoselective synthesis of a C1–C18 segment of the structure of the cytotoxic macrolides amphidinolides G and H is reported. The target compound was retrosynthetically disconnected into three ...fragments. In the synthetic sense, connection of the fragments was made by means of a Stille coupling and a Julia–Kocienski olefination. Precursors from the chiral pool were used as the starting materials.
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A convergent stereoselective synthesis of the bacterial DNA primase inhibitor Sch 642305 and its non-natural epimer at C-4 is described. A key aspect was the construction of a
trans-2,3-disubstituted ...cyclohexanone system by means of a stereoselective Michael addition/α-alkylation sequence. The macrolactone ring of either stereoisomer was created using the Mitsunobu and Yamaguchi procedures, respectively.
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A total, stereoselective synthesis of the naturally occurring, cytotoxic macrolide FD‐891 and of its non‐natural (Z)‐C12 isomer is described. Three fragments of the main carbon chain were ...stereoselectively prepared by using asymmetric aldol and allylation reactions as the key steps. The molecule was then assembled by using two Julia–Kocienski olefinations to connect the three fragments and a Yamaguchi reaction to close the macrolactone ring. Some specific biological properties (cytotoxicity, binding to tubulin) have been determined for both macrolides. The E configuration of the C12–C13 olefinic bond seems to be an important feature in determining the cytotoxicity but the precise biological mechanism of the latter still remains to be cleared.
A stereoselective and convergent synthesis of the cytotoxic macrolide FD‐891 and its non‐natural (Z)‐C12 isomer is described (see scheme). Three building blocks (depicted in different colours) were stereoselectively constructed by using asymmetric aldol and allylation reactions as the key steps, and subsequently assembled by means of Julia–Kocienski olefinations. The macrolactone ring was created by means of a Yamaguchi reaction. Some biological properties (cytotoxicity, binding to tubulin) were determined for both macrolides.
A total synthesis of the naturally occurring, cytotoxic macrolide FD-891 is described. Three fragments were first stereoselectively constructed using mainly asymmetric aldol and allylation reactions. ...The complete framework was then assembled using two Julia−Kocienski olefinations to connect the three fragments and a Yamaguchi reaction to close the macrolactone ring.
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