Advances in flavonoid research since 1992.

https://www.erowid.org/archive/rhodium/pdf/suzuki.cross-coupling.review.1995-1998.pdf

Recent advances in the cross-coupling reactions of organoboron derivatives with organic electrophiles, 1995–1998

Privileged substructures are of potentially great importance in medicinal chemistry. These scaffolds are characterized by their ability to promiscuously bind to a multitude of receptors through a variety of favorable characteristics. This may include presentation of their substituents in a spatially defined manner and perhaps also the ability to directly bind to the receptor itself, as well as exhibiting promising characteristics to aid bioavailability of the overall molecule. It is believed that some privileged substructures achieve this through the mimicry of common protein surface elements that are responsible for binding, such as β- and gamma;-turns. As a result, these structures represent a promising means by which new lead compounds may be identified.

The combinatorial synthesis of bicyclic privileged structures or privileged substructures

Transition metal-catalyzed cross-coupling reactions of alkyl metals and aryl halides or pseudohalides have emerged as a powerful methodology for the formation of Csp3-Csp2 bonds over the past decades.1 However, significant attention has also been focused on Pdand Ni-catalyzed Csp3-Csp2 bond-forming reactions that involve aryl metals and haloalkyl compounds lacking -hydrogen atoms as cross-coupling partners.2 In contrast, until a few years ago, few examples were reported in the literature concerning transition metalcatalyzed reactions of aryl metals with functionalized alkyl halides including R-halocarbonyl compounds and R-bromosulfones bearing -hydrogen atoms,3 and a single example of Pd-catalyzed cross-coupling reaction of aryl metals and unfunctionalized alkyl halides bearing -hydrogen atoms had been described.4 Only in recent years, successful procedures for the Pd-,5 Ni-,6 Rh-,7 Fe-,8 V-,9 Co-,10 and Cu-catalyzed11 cross-coupling reactions of aryl metals and unfunctionalized alkyl halides bearing -hydrogen atoms have been developed.12 Nevertheless, new, effective, and more environmentallybenignmethodologiesfortheformationof(cyclo)alkyl-aryl bonds, which require a reduced number of synthetic operations, have emerged as valuable alternatives to the conventional cross-coupling reactions. These methodologies (Scheme 1) are based on transition metal-catalyzed simple or 2-fold C-H bond functionalization according to the following approaches: (a) highly regioselective Pd-catalyzed direct arylation reactions of unactivated sp3-hybridized C-H bonds with aryl halides (eq a, Scheme 1);13 (b) Pd-catalyzed direct alkylation reactions of aryl C-H bonds with alkyl metals (eq b, Scheme 1);14 Au-15 or Pdcatalyzed16 direct alkylation reactions of aryl C-H bonds with alkyl halides or pseudohalides (eq c, Scheme 1); (d) Pd-catalyzed arylations of unactivated sp3-hybridized C-H bonds with aryl metals (eq d, Scheme 1);14c (e) Pd-, Ru-, or Cu-catalyzed cross-coupling reactions of sp3-hybridized C-H bonds with arylboronic acids using air as oxidant (eq d, Scheme 1);17 and (f) cross-dehydrogenative coupling of alkyl and aryl C-H bonds (eq e, Scheme 1).18 Finally, great attention, particularly in the past decade, has also been focused on the design, development, and application of transition metal-catalyzed coupling reactions of aryl halides and pseudohalides with a wide variety of substrates containing activated sp3-hybridized C-H bonds (eq f, Scheme 1). A mini-review on this topic was published by Scolastico and Poli in 1999,19 and three excellent reviews that concern the results obtained in this rapidly growing area of extensive research by the groups of Miura, Natsume, Hartwig, and Buchwald up to the end of 2002 were published by Miura,20 Hartwig,21 and Lloyd-Jones22 a few years later. However, the reviews by Miura20 and Hartwig21 were limited in that they fundamentally emphasized the author’s own work and * To whom correspondence should be addressed. E-mail: rossi@dcci.unipi.it. Chem. Rev. 2010, 110, 1082–1146 1082

Transition metal-catalyzed direct arylation of substrates with activated sp3-hybridized C-H bonds and some of their synthetic equivalents with aryl halides and pseudohalides.

Anthocyanins and other flavonoids

The absolute configuration of armillol as shown in (6) was determined by applying coupled oscillator theory to the strong negative circular dichroism (c.d.) couplet of (7), utilizing the published atom co-ordinates obtained from X-ray diffraction.

The absolute configuration of the orsellinate of armillol; application of the coupled oscillator theory

The reaction of aryllead(IV) triacetates with benzofuran-3(2H)-one 1 yields the 2,2-diarylated ketone or the monoarylated ketone with the hindered lead reagent 15 2-Phenylthiobenzofuran3(2H)-one 2 was easily arylated with a wide range of aryllead reagents to give arylated ketones in 29–92% yields α-Acetoxylation was observed only as a side reaction with hindered lead reagents, bearing ortho-substituents

Arylation of α-(phenylthio)ketones with aryllead(IV) derivatives: application to the synthesis of 2-arylbenzofuran-3(2H)-one derivatives

Lead(IV) acetate was found to be a suitable dehydrogenating agent for the preparation of 6H-benzofuro[3,2-c]benzopyran from its 6a,11a-dihydro-derivative. The product was also synthesised independently. A scheme for the chemical interconversion of the 6H-benzofuro[3,2-c]benzopyrans and the related isoflavonoids is suggested.

Reactions of 6a,11a-dihydro-6H-benzofuro[3,2-c]benzopyran

Quantitative yields have been obtained in the interconversion of neoflavanoids (II)⇌(IV). An alternative pathway is considered for the synthesis of 4-arylcoumarins without a 6-hydroxy-substituent.

Dervilla M.X. Donnelly

Papers

The absolute configuration of the orsellinate of armillol; application of the coupled oscillator theory

Arylation of α-(phenylthio)ketones with aryllead(IV) derivatives: application to the synthesis of 2-arylbenzofuran-3(2H)-one derivatives

Reactions of 6a,11a-dihydro-6H-benzofuro[3,2-c]benzopyran

Interconversion of neoflavanoids

High-performance liquid chromatographic determination of fomannoxin in European strains of Heterobasidion annosum (Fr.) Bref.