Synthesis of beta,beta-disubstituted vinyl boronates via the ruthenium-catalyzed Alder ene reaction of borylated alkynes and alkenes

Ruthenium-catalyzed Alder ene reactions between borylated alkynes and terminal alkenes give the corresponding beta,beta-disubstituted vinyl boronates with high selectivity for the branched isomer. The stereochemistry of the vinyl boronate moiety was the result of a formal trans addition of the ene subunit across the alkyne, which is the opposite stereochemical outcome observed for other internal alkynes.     

Sequential Pd-catalyzed asymmetric allene diboration/alpha-aminoallylation

Pd-catalyzed enantioselective diboration of prochiral allenes provides adducts which participate in highly selective allylation reactions with primary imines. The allylation product is a vinyl boronate which may be oxidized to give nonracemic Mannich products (87-97% ee). Alternatively, enantiomerically enriched homoallylic amine derivatives may be obtained by protonation and Suzuki cross-coupling of the vinyl boronate.     

Synthesis of functionalized vinyl boronates via ruthenium-catalyzed olefin cross-metathesis and subsequent conversion to vinyl halides

Functionalized vinyl pinacol boronates suitable for Suzuki cross-coupling reactions are synthesized using ruthenium-catalyzed olefin cross-metathesis of 1-propenyl pinacol boronate and various alkenes, including functionalized and 1,1-disubstituted alkenes. The resultant boronate cross products are stereoselectively transformed into predominantly Z-vinyl bromides and E-vinyl iodides. The vinyl bromides may be synthesized in a two-step, one-pot synthesis from a variety of olefins, resulting in a Z-selective formal vinyl bromide cross-metathesis reaction.     

Synthesis of tri-substituted vinyl boronates via ruthenium-catalyzed olefin cross-metathesis

Tri-substituted vinyl pinacol boronates, which are key reactive intermediates in a variety of transformations, are synthesized using ruthenium-catalyzed olefin cross-metathesis of α-substituted vinyl boronates and various alkenes. Cross-metathesis of 2-isopropenyl pinacol boronate proceeds with moderate yield and high Z-selectivity when sterically unhindered cross partners are used. Cross-metathesis of vinyl boronates that possess α-substitution larger than a methyl group is also achieved. Yield and Z-selectivity are lower in these cases, and the success of a cross-metathesis reaction is highly dependent on the steric bulk surrounding the double bond of the α-substituted vinyl boronate.     

Formation of C(sp2)Boronate Esters by Borylative Cyclization of Alkynes Using BCl3

BCl₃ is an inexpensive electrophile which induces the borylative cyclization of a wide range of substituted alkynes to regioselectively form polycycles containing synthetically versatile C(sp²)? boronate esters. It proceeds rapidly, with good yields and is compatible with a range of functional groups and substitution patterns. Intermolecular 1,2‐carboboration of alkynes is also achieved using BCl₃ to generate trisubstituted vinyl boronate esters.     

Formation of C(sp2)?Boronate Esters by Borylative Cyclization of Alkynes Using BCl3

BCl₃ is an inexpensive electrophile which induces the borylative cyclization of a wide range of substituted alkynes to regioselectively form polycycles containing synthetically versatile C(sp²) boronate esters. It proceeds rapidly, with good yields and is compatible with a range of functional groups and substitution patterns. Intermolecular 1,2‐carboboration of alkynes is also achieved using BCl₃ to generate trisubstituted vinyl boronate esters.     

An Alkenyl Boronate as a Monomer for Radical Polymerizations: Boron as a Guide for Chain Growth and as a Replaceable Side Chain for Post‐Polymerization Transformation

The ability of isopropenyl boronate pinacol ester to serve as a monomer in radical polymerizations was established and exploited for the synthesis of polymers that are difficult to access using other polymerization techniques. Although the monomer exhibits an α‐methyl‐substituted unconjugated structure, which is usually unfavorable for radical propagation, both free and controlled radical polymerizations smoothly afford the corresponding polymers. A density‐functional‐theory‐based investigation revealed that the boron atom moderately stabilizes the radical species, which leads to the suppression of the degradative chain transfer to the α‐methyl groups, and thus guides the reaction towards the radical polymerization. The boronyl pendants, which are directly attached to the polymer backbone, can be replaced with ‐OH or ‐NH₂ to yield poly(α‐methyl vinyl amine) or poly(α‐methyl vinyl alcohol), which has been inaccessible by conventional synthetic methods.     

H2‐Acceptorless Dehydrogenative Boration and Transfer Boration of Alkenes Enabled by Zirconium Catalyst

The first example of an efficient and direct dehydrogenative boration of alkenes for vinyl boronate ester synthesis was achieved using a zirconium catalyst. Our methodology avoids using precious transition metals, additional hydrogen acceptors, high temperatures, and long reaction times, which were required to overcome the reducing ability of borane, to give alkyl boronate esters. Detailed mechanistic studies revealed a reversible reaction pathway and further suggested applying the zirconium complex as a “shuttle catalyst” for transfer boration, which thus sidesteps the use of relatively sensitive borane.     

Stereodivergent Olefination of Enantioenriched Boronic Esters

A stereodivergent coupling reaction between vinyl halides and boronic esters is described. This coupling process proceeds without a transition‐metal catalyst, instead proceeding by electrophilic selenation or iodination of a vinyl boronate complex followed by stereospecific syn or anti elimination. Chiral, nonracemic boronic esters could be coupled with complete enantiospecificity. The process enables the highly stereoselective synthesis of either the E or Z alkene from a single isomer of a vinyl coupling partner.     

Visible-Light-Driven Strain-Increase Ring Contraction Allows the Synthesis of Cyclobutyl Boronic Esters

There are a limited number of ring-contraction methodologies which convert readily available five-membered rings into strained four-membered rings. Here we report a photo-induced radical-mediated ring contraction of five-membered-ring alkenyl boronate complexes into cyclobutanes. The process involves the addition of an electrophilic radical to the electron-rich alkenyl boronate complex, leading to an α-boryl radical. Upon one-electron oxidation, ring-contractive 1,2-metalate rearrangement occurs to give a cyclobutyl boronic ester. A range of radical precursors and vinyl boronates can be employed, and chiral cyclobutanes can be accessed with high levels of stereocontrol. The process was extended to the preparation of benzofused cyclobutenes and the versatility of the boronic ester was demonstrated by conversion to other functional groups.     

Visible-Light-Promoted Reaction of N-Hydroxyphthalimide Esters with Vinyl Boronic Pinacol Ester

A novel and easy-to-execute light-driven protocol for the preparation of alkyl boronic acid pinacol esters from vinyl boronate using N-hydroxyphthalimide esters as the potential precursor is described. In this photochemical protocol, the N-hydroxyphthalimide ester's fragmentation generates C-centered radicals, which undergo a radical Michael addition to vinyl boronic pinacol ester furnishing the desired products. A good substrate scope having various functionalities is presented and good to high yields are obtained.     

Deprotection of pinacolyl boronate esters by transesterification with polystyrene-boronic acid

Mild deprotection of pinacolyl boronate esters to the corresponding boronic acids was achieved in the presence of excess polystyrene-boronic acid via a transesterification process. The procedure allows for the cleavage of pinacolyl boronate esters in the presence of sensitive functional groups.     

Visible‐Light‐Driven Strain‐Increase Ring Contraction Allows the Synthesis of Cyclobutyl Boronic Esters

There are a limited number of ring‐contraction methodologies which convert readily available five‐membered rings into strained four‐membered rings. Here we report a photo‐induced radical‐mediated ring contraction of five‐membered‐ring alkenyl boronate complexes into cyclobutanes. The process involves the addition of an electrophilic radical to the electron‐rich alkenyl boronate complex, leading to an α‐boryl radical. Upon one‐electron oxidation, ring‐contractive 1,2‐metalate rearrangement occurs to give a cyclobutyl boronic ester. A range of radical precursors and vinyl boronates can be employed, and chiral cyclobutanes can be accessed with high levels of stereocontrol. The process was extended to the preparation of benzofused cyclobutenes and the versatility of the boronic ester was demonstrated by conversion to other functional groups.     

On the mechanism and origin of the stereoselectivity in iodo-deboronation and chloro-deboronation of hindered alkenyl boronate esters using either ICl-NaOMe or ICl-pyridine

Conversion of hindered alkenyl boronate esters into the corresponding iodoalkene, or alkenyl chloride can be carried out stereoselectively using ICl. In the presence of NaOMe, direct reaction of ICl is favoured yielding the E-iodoalkene, however, the reaction with ICl followed by NaOMe can be used to give different major alkenyl iodide and chloride products, depending upon reaction temperature, ICl source and alkenyl boronate stereoelectronics.     

Enantiospecific Trifluoromethyl‐Radical‐Induced Three‐Component Coupling of Boronic Esters with Furans

In the presence of trifluoromethylsulfonium reagents, boronate complexes derived from 2‐lithio furan and non‐racemic secondary and tertiary alkyl or aryl boronic esters undergo deborylative three‐component coupling to give the corresponding 2,5‐disubstituted furans with excellent levels of enantiospecificity. The process proceeds via the reaction of boronate complexes with a trifluoromethyl radical, which triggers 1,2‐metallate rearrangement upon single‐electron oxidation. Alternative electrophiles can also be used in place of trifluoromethylsulfonium reagents to effect similar three‐component coupling reactions.     

Regiochemical control in the metal-catalyzed transposition of allylic silyl ethers

A novel mode of regiochemical control over the allylic [1,3]-transposition of silyloxy groups catalyzed by Re2O7 has been developed. This strategy relies on a cis-oriented vinyl boronate, generated from the Alder-ene reaction of homoallylic silyl ethers and alkynyl boronates, to trap out the allylic hydroxyl group. The resulting cyclic boronic acids are excellent partners for cross-coupling reactions. High chirality transfer is observed for the rearrangement of enantioenriched allylic silyl ethers.     

Vinyl MIDA boronate: a readily accessible and highly versatile building block for small molecule synthesis

Iterative cross-coupling represents a potentially general approach for the simple, efficient, and flexible construction of natural products, pharmaceuticals, and materials. N-Methyliminodiacetic acid (MIDA) boronates represent a promising platform for the development of this type of synthesis strategy. This report describes the discovery that vinyl MIDA boronate (1) is an air- and chromatographically stable compound that can be conveniently prepared on a multigram scale and serve as a versatile starting material for the preparation of a range of new MIDA boronate building blocks. Analogous to tert-butylethylene, 1 is also an excellent substrate for olefin cross-metathesis, providing access to a range of trans-alkenyl MIDA boronates as single stereoisomers. An improved synthesis of the very versatile bifunctional building block trans-(2-bromovinyl) MIDA boronate (2) is also described. Collectively, these results contribute to the expanding generality of the iterative cross-coupling approach.     

Asymmetric total synthesis of (-)-spirofungin A and (+)-spirofungin B

[chemical reaction: see text]. The stereocontrolled total synthesis of (-)-spirofungin A (1) and (+)-spirofungin B (2a), polyketide-type antibiotics having various antifungal activities, has been achieved employing the Weinreb amide 8, the alkyne 9, and the vinyl boronate 5 readily available from the common intermediate 10. The first synthesis proceeded with a longest linear sequence of 31 steps, affording (-)-1 and (+)-2a in 7.9% and 5.2% overall yields, respectively.     

Stereodivergent Zweifel Olefination and its Mechanistic Dichotomy

Stereoselective Zweifel olefination using boronate complexes carrying two different reactive π-systems was achieved to synthesize vinyl heteroarenes and conjugated 1,3-dienes in good yield and up to 100 % stereoselectivity, which remains unexplored until now. Most importantly, we report the unprecedented formation of E vs. Z-vinyl heteroarenes for different heteroarenes under identical conditions. Density functional theory (DFT) investigations unveil the mechanistic dichotomy between olefin and heteroarene activation followed by 1,2-migration, leading to E or Z-vinyl heteroarenes respectively. We also report a previously unknown reversal of stereoselectivity by using 2,3-Dichloro-5,6-dicyano-1,4-benzoquinone (DDQ) as an electrophile. The Zweifel olefination using a boronate complex that carries two different olefins was previously unexplored due to significant challenges associated with the site-selective activation of olefins. We have solved this problem and reported the site-selective activation of olefins for the stereoselective synthesis of 1,3-dienes.     

An Exploratory Study of Silylated Amino Boronic Ester Chemistry

Diisopropyl [bis(trimethylsilylamino)methyl]-boronate, the analogous pinacol boronic ester ( 3 ), andpinacol [(2,2,5,5-tetramethyl-2,5,1-disilazol-1-yl)-methyl]boronate ( 8 ) were prepared from the corresponding (bromomethyl)boronic ester 1 or 2 and silylated lithium amide. Reaction of 3 or 8 with (dichloromethyl)lithium yielded the corresponding [1-chloro-2-(silylated amino)ethyl]boronate 4 or 9 . Further transformations of 4 to methylthio derivative 5 and dimethylamino derivative 7 as well as conversion of 5 to ureido derivatives 6 are described. (S,S)-1,2-Dicyclohexylethanediol [1-chloro-2-(trityloxy)-ethyl]boronate ( 13 ) has been converted to bis(tri-methylsilyl)amino derivative 14 and formamido derivative 15 as well as to N-benzyl analogs 18 and 19 . Attempted chain extensions of 14, silylated 15, or 19 with (dichloromethyl)lithium indicated that the alkyl migration from boron to carbon is slow and incomplete. © 1997 John Wiley & Sons, Inc. Heteroatom Chem 8: 487–494, 1997