Vittorio Farina

New perspectives in the cross-coupling reactions of organostannanes

The palladium-catalyzed coupling of organostannanes (the StiIle reaction) can be accelerated in a number of ways. Three approaches are described here. In the first one, it is shown that ligands of low donicity dramatically accelerate the Stille coupling, and a simple hnetic scheme is presented. In the second approach, intramolecular nucleophilic assistance at tin is provided. The mechanistic implications of our data are briejy discussed. Finally, bimetallic catalysis (in this case with Cu(I) salts) is shown to lead to fmter coupling rates and better selectivities.

Stereoselective C-glycosylation reactions with arylzinc reagents.

A general, transition-metal-free, highly stereoselective cross-coupling reaction between glycosyl bromides and various arylzinc reagents leading to β-arylated glycosides is reported. The stereoselectivity of the reaction is explained by invoking anchimeric assistance via a bicyclic intermediate. Stereochemical probes confirm the participation of the 2-pivaloyloxy group. Finally, this new method was applied to a short and efficient stereoselective synthesis of Dapagliflozin and Canagliflozin.

SOLID PHASE SYNTHESIS OF ARYL AMINES VIA PALLADIUM CATALYZED AMINATION OF RESIN-BOUND AROMATIC BROMIDES

Abstract Polymer-bound aromatic bromides were found to readily undergo Pd-catalyzed amination with a number of primary and secondary alkyl- and arylamines to give, after cleavage from the support, a variety of arylamine products.

Optimized Stille coupling reactions catalyzed by palladium on carbon with CuI as cocatalyst

Abstract The coupling reaction of aryl and vinyl iodides, bromides, and triflates with organostannanes can be effectively conducted using palladium on carbon as a source of Pd0. The yield and rate of reaction are significantly affected by the addition of copper iodide as co-catalyst and triphenylarsine as ligand.

One-pot and regiospecific synthesis of 2,3-disubstituted indoles from 2-bromoanilides via consecutive palladium-catalyzed Sonogashira coupling, amidopalladation, and reductive elimination.

A practical one-pot and regiospecific three-component process for the synthesis of 2,3-disubstituted indoles from 2-bromoanilides was developed via consecutive palladium-catalyzed Sonogashira coupling, amidopalladation, and reductive elimination.

On the mechanism of cine substitution in the Stille reaction: New evidence for the intermediacy of Pd(0) carbenes

Abstract A dihydronaphthalene stannane was found to couple with aryl iodides to give exclusively cine substitution instead of the expected Stille product. A crossover study ruled out a mechanism previously proposed that included a disfavored anti beta-elimination of Pd-H, and provides further evidence for the involvement of Pd(0) carbenes in these processes.

Enantioselective synthesis of the (syn,anti)-1-amino-2,3-diol subunit of renin inhibitors by reaction of β-Lactams with a Grignard reagent

A new approach to the BOC-protected amino diol 1a via the opening of 3,4-cis-disubstituted β-lactam 3 with isobutylmagnesium chloride is described. Nonracemic β-lactam 3 could be obtained by enzymatic resolution of the 3-acetoxy-β-lactam 4 or from a chiral precursor, methyl (R)-(−)-mandelate.

Crystallization-induced asymmetric transformations and self-regeneration of stereocenters (SROSC): enantiospecific synthesis of α-benzylalanine and hydantoin BIRT-377

Abstract N-Isobutoxycarbonyl protected l -alanine was condensed with 4-phenylbenzaldehyde in a crystallization-controlled process to give the corresponding cis-oxazolidinone derivative as the sole product in high yield; this underwent enolization and benzylation with the typical high degree of stereoselectivity observed in the SROSC involving this class of compounds.

5 Paclitaxel (Taxol®) chemistry and structure— Activity relationships

Publisher Summary This chapter reviews paclitaxel chemistry and structure–activity relationships (SAR). At least three functional elements of paclitaxel—that is, the C-13 side chain, C-2, and C-4 esters—are intimately involved in interactions at the binding site. C-1 substitution does not imperil C-13 side chain introduction for biological evaluation. In search of a suitable C-1 protecting group, Chen and co-workers utilized the novel dimethylsilane (DMS) group. Selective removal of DMS from C-1 is accomplished with tetrabutylammonium fluoride at 0°C. C-1-Benzoyl-2-deoxybaccatin is converted to the corresponding C-7 silylated analog via a desilylation or mono-silylation sequence. To assess the contribution of the C-2 benzoate moiety to binding, a selective procedure for debenzoylation at C-2 is needed. Under basic conditions, C-10 is deacylated first, and in certain cases, even the C-4 acetate is more labile than the C-2 benzoate. Special conditions are therefore needed for selective C-2 deacylation. Preparation of 4-deacetyltaxol can be carried out quite efficiently beginning with paclitaxel, and using the selective 2,4-deacylation reaction.

Anionic N-Fries Rearrangement of N-Alkyl-2-iodo Anilides Induced by Iodine−Magnesium Exchange: Application for Synthesis of Strained 1,2,3-Trisubstituted Indoles

A superior, mild, high-yielding one-pot process for rapid access to oxo anilides has been developed that involves three cascade reactions: iodine-magnesium exchange, regiospecific ortho N-Fries rearrangement, and in situ trapping of the formed aniline anion. Coupled with McMurry cyclization, the two-step process allows ready synthesis of strained 1,2,3-trisubstituted indoles regioselectively.