Sequential iodine-mediated diallylsilane rearrangement/asymmetric dihydroxylation: Synthesis and reactions of enantioenriched oxasilacycles.

Products from an iodine-mediated diallylsilane rearrangement were taken into an asymmetric dihydroxylation (AD) reaction resulting in the formation of diastereomeric 6-membered oxasilacycles. Removal of the epimeric stereocenter among this mixture of diastereomers by elimination of iodine produced a single enantioenriched cyclic allyl silyl ether. The resulting allyl silane was then successfully engaged in several further transformations, providing an alternative means to prepare useful intermediates for enantioselective synthesis.

Arylphosphonate-Directed Ortho C-H Borylation: Rapid Entry into Highly-Substituted Phosphoarenes.

Phosphonate-directed ortho C-H borylation of aromatic phosphonates is reported. Using simple starting materials and commercially accessible catalysts, this method provides steady access to o-phosphonate arylboronic esters bearing pendant functionality and flexible substitution patterns. These products serve as flexible precursors for a variety of highly substituted phosphoarenes, and in situ downstream functionalization of the products is described.

Phosphine-Directed sp3 C-H, C-O, and C-N Borylation.

Benzylic C-H borylation reactions are limited, requiring new approaches to exploit their reactivity for efficient selective functionalization. The recent development of phosphine-directed C-H borylation of arenes has now been extended to benzylic substrates, providing high yield of the mono- and geminal bis-borylation products. Attempts to borylate the C-H bond α to a benzylic ether or amine resulted in C-O and C-N borylation, followed by C-H borylation to provide geminal bis-borylated products.

ß-Silyloxy Allylboronate Esters through an Aldehyde Borylation/Homologation Sequence.

The areas of carbonyl borylation and the homologation of carbon-boron bonds have provided a number of fruitful methods in organic synthesis. Combining these approaches, the homologation of α-oxyboronate esters, provides pathways to access complex organoboronate esters stereoselectively. To this end, the homologation of α-silyloxyboronate esters with lithiated allyl chlorides to form ß-silyloxy allylboronate esters is reported. Direct oxidation of the homologation products provides ß-silyloxy allyl alcohols in good yield. The homologation provides a range of allylic alcohols, albeit with low diastereoselectivity.

Chemoselective Carbonyl Allylations with Alkoxyallylsiletanes.

Alkoxyallylsiletanes are capable of highly chemo- and diastereoselective carbonyl allylsilylations. Reactive substrates include salicylaldehydes and glyoxylic acids. Chemoselectivity in these reactions is thought to arise from a mechanism involving first exchange of the alkyoxy group on silicon with a substrate hydroxyl followed by activation of a nearby carbonyl by the Lewis acidic siletane and intramolecular allylation. In this way, substrates containing multiple reactive carbonyl groups (e.g., dialdehyde or triketone) can be selectively monoallylated, even overcoming inherent electrophilicity bias.

Accessing Ambiphilic Phosphine Boronates through C-H Borylation by an Unforeseen Cationic Iridium Complex.

Ambiphilic molecules, which contain a Lewis base and Lewis acid, are of great interest based on their unique ability to activate small molecules. Phosphine boronates are one class of these substrates that have interesting catalytic activity. Direct access to these phosphine boronates is described through the iridium-catalyzed C-H borylation of phosphines. An unconventional cationic iridium catalyst was identified as optimal for a range of phosphines, providing good yields and selectivity across a diverse class of phosphine boronates (isolated as the borane-protected phosphine). A complimentary catalyst system (quinoline-based silane ligand with [(COD)IrOMe]2 ) was optimal for biphenyl-based phosphines. Selective polyborylation was also shown providing bis- and tris-borylated phosphines. Deprotection of the phosphine boronate provided free ambiphilic phosphine boronates, which do not have detectable interactions between the phosphorus and boron atoms in solution or the solid state.

Synthesis of Biaryl Ethers by the Copper-Catalyzed Chan-Evans-Lam Etherification from Benzylic Amine Boronate Esters.

The copper-catalyzed etherification of ortho-borylated benzylic amines with phenols has been achieved to provide biaryl ethers that are prevalent in biologically active compounds. A variety of substitution patterns on the aryl boronate ester and the phenol are tolerated under the reaction conditions, providing moderate to high yields. A competition reaction between phenol and aniline revealed condition-dependent selectivity in which the phenol could be highly favored over the aniline.

Selective Formation of ortho-Aminobenzylamines by the Copper-Catalyzed Amination of Benzylamine Boronate Esters.

The copper-catalyzed coupling between benzylamino boronate esters and aryl amines has been investigated. Formation of ortho-aminobenzylamines was achieved under oxidative conditions in the presence of copper(II) acetate. The major side product of the transformation is the homocoupling of the aryl boronate ester. The formation of the desired diamines was found to be improved in the absence of base, increasing selectivity over the homocoupled product. Both electron-donating and electron-withdrawing substituents are tolerated on both the boronate ester substrate and the aniline coupling partner under the reaction conditions. The presence of the adjacent benzylamine moiety appears to enhance the reactivity of the boronate ester and influence the resulting product distribution, likely by affecting the competing rates of transmetalation in the catalytic cycles.

Stereoselective formation of trisubstituted vinyl boronate esters by the acid-mediated elimination of α-hydroxyboronate esters.

The copper-catalyzed diboration of ketones followed by an acid-catalyzed elimination leads to the formation of 1,1-disubstituted and trisubstituted vinyl boronate esters with moderate to good yields and selectivity. Addition of tosic acid to the crude diboration products provides the corresponding vinyl boronate esters upon elimination. The trisubstituted vinyl boronate esters are formed as the (Z)-olefin isomer, which was established by subjecting the products to a Suzuki-Miyaura coupling reaction to obtain alkenes of known geometry.

Phosphine-directed C-H borylation reactions: facile and selective access to ambiphilic phosphine boronate esters.

Ambiphilic ligands have received considerable attention over the last two decades due to their unique reactivity as organocatalysts and ligands. The iridium-catalyzed C-H borylation of phosphines is described in which the phosphine is used as a directing group to provide selective formation of arylboronate esters with unique scaffolds of ambiphilic compounds. A variety of aryl and benzylic phosphines were subjected to the reaction conditions, selectively providing stable, isolable boronate esters upon protection of the phosphine as the borane complex. After purification, the phosphine-substituted boronate esters could be deprotected and isolated in pure form.

Stereocontrolled synthesis of 1,3-diols from enones: cooperative Lewis base-mediated intramolecular carbonyl hydrosilylations.

A streamlined synthesis of ß-hydroxy ketone substrates has been developed to further investigate a recently discovered cooperative Lewis base-mediated intramolecular carbonyl hydrosilylation reaction. The synthesis features an enone ß-borylation/oxidation sequence that has proven to be quite general and high-yielding. This has allowed for additional investigations into the diastereoselectivity of the hydrosilylation reaction through the preparation of important polyketide fragments.

Alkoxide-catalyzed reduction of ketones with pinacolborane.

The reduction of ketones with pinacolborane (4,4,5,5-tetramethyl-1,3,2-dioxaborolane) is catalyzed by 5 mol % NaOt-Bu at ambient temperature. The reaction is high yielding and general, providing complete conversion of aryl and dialkyl ketones. Although spectroscopic studies of the active hydride source in benzene-d(6) were complicated due to poor solubility, the data are consistent with the active hydride source being the trialkoxyborohydride, which is believed to be present in low concentration under the reaction conditions. Performing analogous studies in tetrahydrofuran resulted in a complex equilibrium between several different boron-containing species in which the trialkoxyborohydride compound was the major species.

Copper-Catalyzed Enantioselective Synthesis of ß-Boron ß-Amino Esters.

In this report, the enantioselective, copper-catalyzed borylation of ß-amidoacrylates is disclosed. A broad variety of biologically important α-aminoboronates has been prepared with consistently high levels of enantiocontrol using an inexpensive copper catalyst and a commercially available chiral ligand. The method can be applied to the synthesis of novel boron-containing dipeptides and hemiboronates.

Formation and reactivity of silacyclopropenes derived from siloxyalkynes: stereoselective formation of 1,2,4-triols.

Silver phosphate-catalyzed silylene transfer to siloxyalkynes provided silacyclopropenes possessing a silyl enol ether functional group. Copper-catalyzed insertions of carbonyl compounds afforded the corresponding oxasilacyclopentenes. The embedded silyl enol ether functionality was treated with various aldehydes and a catalytic amount of Sc(OTf)3 to provide dioxasilacycloheptanones, which resulted from an aldol addition/rearrangement. Stereoselective reduction or allylation of the cyclic ketone, followed by n-Bu4NF deprotection, provided high yields of 1,2,4-triols possessing four contiguous stereocenters.

Facile formation of ß-hydroxyboronate esters by a Cu-catalyzed diboration/Matteson homologation sequence.

The copper-catalyzed diboration of aldehydes was used in conjunction with the Matteson homologation, providing the efficient synthesis of ß-hydroxyboronate esters. The oxygen-bound boronate ester was found to play a key role in mediating the homologation reaction, which was compared to the α-hydroxyboronate ester (isolated hydrolysis product). The synthetic utility of the diboration/homologation sequence was demonstrated through the oxidation of one product to provide a 1,2-diol.

Iridium-catalyzed, substrate-directed C-H borylation reactions of benzylic amines.

The iridium-catalyzed arene C-H borylation reaction of benzylic amines has been developed, which inverts the typical steric-controlled product distribution to provide ortho-substituted boronate esters. Picolylamine was found to be an ideal ligand to replace 4,4'-di-tert-butylbipyridine to induce the directing effect. Preliminary experiments are consistent with a mechanism involving dissociation of one amine of the hemilabile diamine ligand.

Copper-catalyzed diboration of ketones: facile synthesis of tertiary alpha-hydroxyboronate esters.

The diboration of ketones with the (ICy)CuOt-Bu catalyst was developed to provide access to tertiary alpha-hydroxyboronate esters. The (ICy)CuOt-Bu catalyst was generated in situ with (ICy)CuCl and NaOt-Bu to afford a more efficient catalyst than the preformed (ICy)CuOt-Bu. These conditions result in the diboration of various ketones in toluene at 50 degrees C in 2-22 h. Treatment of the resulting products with silica gel affords the corresponding alpha-hydroxyboronate esters.

Synthesis of Ruthenium Boryl Analogues of the Shvo Metal-Ligand Bifunctional Catalyst.

Metal boryl complexes have received significant attention in the literature in recent years due to their role as key intermediates in a number of metal-catalyzed borylation reactions. The ligand scaffold is known to have a significant impact on the observed reactivity of these metal boryl complexes. A synthetic strategy to access ruthenium boryl analogues of the Shvo metal-ligand catalysts is described. Heating a precursor to Shvo's catalyst (1) with bis(catecholato)diboron at 50 °C provided ruthenium boryl complex 3 [2,5-Ph(2)-3,4-Tol(2)(η(5)-C(4)COBcat)Ru(CO)(2)Bcat] (Bcat = catecholatoboryl). Addition of bis(catecholato)diboron to complex 1 in the presence of a phenol results in ruthenium boryl complex5 [2,5-Ph(2)-3,4-Tol(2)(η(5)-C(4)COH)Ru(CO)(2)Bcat] at 22 °C in 30% isolated yield. A single crystal X-ray analysis of complex 5 confirmed the assigned structure. An improved synthesis of ruthenium boryl complex 5 was developed by the in situ formation of complex 3 [2,5-Ph(2)-3,4-Tol(2)(η(5)-C(4)COBcat)Ru(CO)(2)Bcat] followed by addition of the phenol, resulting in a 51% yield.

Alkylidenesilacyclopropanes derived from allenes: applications to the selective synthesis of triols and homoallylic alcohols.

Several alkylidenesilacyclopropanes were prepared by silver-mediated silylene transfer to allenes. Oxasilacyclopentanes derived from allenes were prepared with high regio- and diastereoselectivity by a two-step, one-flask silacyclopropanation/carbonyl insertion reaction. Triols and homoallylic alcohols were formed diastereoselectively by functionalizing the oxasilacyclopentanes. An optically active allene (>98% ee) was utilized to synthesize an enantiopure homoallylic alcohol in 96% ee.

Intramolecular trapping of an intermediate in the reduction of imines by a hydroxycyclopentadienyl ruthenium hydride: support for a concerted outer sphere mechanism.

Reduction of imines by [2,5-Ph2-3,4-Tol(2)(eta(5)-C(4)COH)]Ru(CO)2H (1) produces kinetically stable ruthenium amine complexes. Reduction of an imine possessing an intramolecular amine was studied to distinguish between inner sphere and outer sphere mechanisms. 1,4-Bn(15)NH(c-C(6)H(10))=NBn (12) was reduced by 1 in toluene-d8 to give 85% of [2,5-Ph2-3,4-Tol(2)(eta(4)-C(4)CO)](CO)(2)RuNHBn(c-C(6)H(10))(15)NHBn (16-RuN,15N), resulting from coordination of the newly formed amine to the ruthenium center, and 15% of trapping product [2,5-Ph2-3,4-Tol(2)(eta(4)-C(4)CO)](CO)(2)Ru(15)NHBn(c-C(6)H(10))NHBn (16-Ru(15)N,N), resulting from coordination of the intramolecular trapping amine. These results provide support for an outer sphere transfer of hydrogen to the imine to generate a coordinatively unsaturated intermediate, which can be trapped by the intramolecular amine. An opposing mechanism, requiring coordination of the imine nitrogen to ruthenium prior to hydrogen transfer, cannot readily explain the observation of the trapping product 16-Ru(15)N,N.