Copper‐Catalyzed Triboration: Straightforward,Atom‐Economical Synthesis of 1,1,1‐Triborylalkanes from Terminal Alkynes and HBpin

A convenient and efficient one‐step synthesis of 1,1,1‐triborylalkanes was achieved via sequential dehydrogenative borylation and double hydroborations of terminal alkynes with HBpin (HBpin=pinacolborane) catalyzed by inexpensive and readily available Cu(OAc)₂. This process proceeds under mild conditions, furnishing 1,1,1‐tris(boronates) with wide substrate scope, excellent selectivity, and good functional‐group tolerance, and is applicable to gram‐scale synthesis without loss of yield. The 1,1,1‐triborylalkanes can be used in the preparation of α‐vinylboronates and borylated cyclic compounds, which are valuable but previously rare compounds. Different alkyl groups can be introduced stepwise via base‐mediated deborylative alkylation to produce racemic tertiary alkyl boronates, which can be readily transformed into useful tertiary alcohols.     

Site‐Selective 1,2‐Dicarbofunctionalization of Vinyl Boronates through Dual Catalysis

A modular, site‐selective 1,2‐dicarbofunctionalization of vinyl boronates with organic halides through dual catalysis is described. This reaction proceeds under mild conditions and is characterized by excellent chemo‐ and regioselectivity. It thus represents a complementary new technique for preparing densely functionalized alkyl boron architectures from simple and accessible precursors.     

Zinc‐Catalyzed Borylation of Primary,Secondary and Tertiary Alkyl Halides with Alkoxy Diboron Reagents at Room Temperature

A new catalytic system based on a Zn^II NHC precursor has been developed for the cross‐coupling reaction of alkyl halides with diboron reagents, which represents a novel use of a Group XII catalyst for C? X borylation. This approach gives borylations of unactivated primary, secondary, and tertiary alkyl halides at room temperature to furnish alkyl boronates, with good functional‐group compatibility, under mild conditions. Preliminary mechanistic investigations demonstrated that this borylation reaction seems to involve one‐electron processes.     

Regio‐ and Enantioselective Synthesis of Trifluoromethyl‐Substituted Homoallylic α‐Tertiary NH2‐Amines by Reactions Facilitated by a Threonine‐Based Boron‐Containing Catalyst

A method for catalytic regio‐ and enantioselective synthesis of trifluoromethyl‐substituted and aryl‐, heteroaryl‐, alkenyl‐, and alkynyl‐substituted homoallylic α‐tertiary NH₂‐amines is introduced. Easy‐to‐synthesize and robust N‐silyl ketimines are converted to NH‐ketimines in situ, which then react with a Z‐allyl boronate. Transformations are promoted by a readily accessible l ‐threonine‐derived aminophenol‐based boryl catalyst, affording the desired products in up to 91 % yield, >98:2 α:γ selectivity, >98:2 Z:E selectivity, and >99:1 enantiomeric ratio. A commercially available aminophenol may be used, and allyl boronates, which may contain an alkyl‐, a chloro‐, or a bromo‐substituted Z‐alkene, can either be purchased or prepared by catalytic stereoretentive cross‐metathesis. What is more, Z‐trisubstituted allyl boronates may be used. Various chemo‐, regio‐, and diastereoselective transformations of the α‐tertiary homoallylic NH₂‐amine products highlight the utility of the approach; this includes diastereo‐ and regioselective epoxide formation/trichloroacetic acid cleavage to generate differentiated diol derivatives.     

Visible Light‐Induced Room‐Temperature Heck Reaction of Functionalized Alkyl Halides with Vinyl Arenes/Heteroarenes

The first visible light‐induced Pd‐catalyzed Heck reaction of α‐heteroatom substituted alkyl iodides and ‐bromides with vinyl arenes/heteroarenes has been developed. This transformation efficiently proceeds at room temperature and enables synthesis of valuable functionalized allylic systems, such as allylic silanes, boronates, germanes, stannanes, pivalates, phosphonates, phthalimides, and tosylates from the corresponding α‐substituted methyl iodides. Notably, synthesis of the latter substrates failed under existing thermally induced Pd‐catalyzed conditions, which highlights the importance of visible light for this transformation.     

Stereocontrolled Synthesis of Vinyl Boronates and Vinyl Silanes via Atom‐Economical Ruthenium‐Catalyzed Alkene–Alkyne Coupling

The synthesis of vinyl boronates and vinyl silanes was achieved by employing a Ru‐catalyzed alkene–alkyne coupling reaction of allyl boronates or allyl silanes with various alkynes. The double bond geometry in the generated vinyl boronates can be remotely controlled by the juxtaposing boron‐ and silicon groups on the alkyne substrate. The synthetic utility of the coupling products has been demonstrated in a variety of synthetic transformations, including iterative cross‐coupling reactions, and a Chan‐Lam‐type allyloxylation followed by a Claisen rearrangement. A sequential one‐pot alkene‐alkyne‐coupling/allylation‐sequence with an aldehyde to deliver a highly complex α‐silyl‐β‐hydroxy olefin with a handle for further functionalization was also realized.     

Diastereocontrolled Monoprotodeboronation of β‐Sulfinimido gem‐Bis(boronates): A General and Stereoselective Route to α,β‐Disubstituted β‐Aminoalkylboronates

β‐Aminoalkylboronic acids are bioisosteres of the pharmaceutically important class of β‐amino acids but few stereoselective methods exist for their preparation. The 1,2‐addition of lithiated 1,1‐diborylalkanes onto chiral N‐tert‐butanesulfinyl aldimines produces β‐sulfinimido gem‐bis(boronates) in good to excellent yields with high diastereoselectivity. The optimized conditions involve the use of rubidium fluoride and water, and are compatible with functionalized alkyl, aryl, alkenyl, and alkynyl substituents. Under these conditions, the geminal quaternary alkyl bis(pinacolatoboryl) intermediates undergo a highly diastereoselective monoprotodeboronation to afford a wide range of syn‐α,β‐disubstituted β‐aminoalkylboronates. This novel application of protodeboronation chemistry was shown to result from a kinetically controlled, diastereotopic‐group‐selective B?C bond protolysis dictated by the configuration of the adjacent stereogenic C?N center. Facile acidic cleavage of the sulfinimide auxiliary produces the free aminoboronates with high enantiomeric purity.     

Versatile Homoallylic Boronates by Chemo‐, SN2′‐, Diastereo‐ and Enantioselective Catalytic Sequence of Cu−H Addition to Vinyl‐B(pin)/Allylic Substitution

A highly chemo‐, diastereo‐ and enantioselective catalytic method that efficiently combines a silyl hydride, vinyl‐B(pin) (pin=pinacolato) and (E)‐1,2‐disubstituted allylic phosphates is introduced. Reactions, best promoted by a Cu‐based complex with a chiral sulfonate‐containing N‐heterocyclic carbene, are broadly applicable. Aryl‐, heteroaryl‐, alkenyl‐, alkynyl‐ and alkyl‐substituted allylic phosphates may thus be converted to the corresponding homoallylic boronates and then alcohols (after C−B bond oxidation) in 46–91 % yield and in up to >98 % S_N2′:S_N2 ratio, 96:4 diastereomeric ratio and 98:2 enantiomeric ratio. The reasons why an NHC−Cu catalyst is uniquely effective (vs. the corresponding phosphine systems) and the basis for different trends in stereoselectivity are provided with the aid of DFT calculations.     

A Four‐Component Reaction for the Synthesis of Dioxadiazaborocines

A four‐component reaction for the synthesis of heterocyclic boronates is reported. Readily available hydrazides, α‐hydroxy aldehydes, and two orthogonally reactive boronic acids are combined in a single step to give structurally distinct bicyclic boronates, termed dioxadiazaborocines (DODA borocines). In this remarkable process, one boronic acid reacts as a carbon nucleophile and the other as a boron electrophile to provide enantio‐ and diastereomerically pure heterocyclic boronates with multiple stereocenters in high yields.     

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.     

Aminoazanium of DABCO: An Amination Reagent for Alkyl and Aryl Pinacol Boronates

The aminoazanium of DABCO (H₂N‐DABCO) has been developed as a general and practical amination reagent for the direct amination of alkyl and aryl pinacol boronates. This compound is stable and practical for use as a reagent. Various primary, secondary. and tertiary alkyl?Bpin and aryl?Bpin substrates were aminated to give the corresponding amine derivatives. The amination is stereospecific. The anti‐Markovnikov hydroamination of olefins was easily achieved by catalytic hydroboration with HBpin and in subsequent situ amination using H₂N‐DABCO. Moreover, the combination of 1,2‐diboration of olefins, using B₂pin₂, with this amination process achieved the unprecedented 1,2‐diamination of olefins. The amination protocol was also successfully extended to aryl pinacol boronates.     

Cobalt‐Catalyzed Regio‐ and Stereoselective Hydroboration of Allenes

An efficient pincer‐ligand‐based cobalt‐complex‐catalyzed allene hydroboration affording Z‐allylic boronates is described. The reaction demonstrates an excellent regio‐ as well as Z‐stereoselectivity and a wide substrate scope that tolerates many functional groups. Based on solvent‐assisted electrospray ionization mass spectrometry (SAESI‐MS) studies, a rationale for the cobalt‐catalyzed hydroboration involving the highly selective insertion of an allene into the Co?H bond to form Z‐allylic cobalt intermediates is proposed.     

Cross‐Coupling Reaction of Saccharide‐Based Alkenyl Boronic Acids with Aryl Halides: The Synthesis of Bergenin

A convenient synthetic pathway enabling D ‐glucal and D ‐galactal pinacol boronates to be prepared in good isolated yields was achieved. Both pinacol boronates were tested in a series of cross‐coupling reactions under Suzuki–Miyaura cross‐coupling conditions to obtain the corresponding aryl, heteroaryl, and alkenyl derivatives in high isolated yields. This methodology was applied to the formal synthesis of the glucopyranoside moiety of papulacandin D and the first total synthesis of bergenin.     

From Ynamides to Highly Substituted Benzo[b]furans: Gold(I)‐Catalyzed 5‐endo‐dig‐Cyclization/Rearrangement of Alkylic Oxonium Intermediates

A series of arylynamides with alkyloxy groups at the ortho position of the aryl group was prepared through a short alkylation/cross‐coupling/amidation sequence. The gold‐catalyzed conversion of these substrates combined both C? O and C? C formation steps, thus providing benzofurans with amine functionalities at the 2‐position and alkyl groups at the 3‐position. Cross‐over experiments showed that the alkyl‐migration step was an intermolecular process. X‐ray crystal‐structure analysis of two of the products supported our structural assignment. In some cases, the corresponding benzofurans without the alkyl group at the 3‐position were obtained as side‐products, which were formed through a competing protodeauration process.     

Combined 1H, 13C and 11B NMR and mass spectral assignments of boronate complexes of D‐(+)‐glucose,D‐(+)‐mannose,methyl‐α‐D‐glucopyranoside,methyl‐β‐D‐galactopyranoside and methyl‐α‐D‐mannopyranoside

Complex formation between N‐butylboronic acid and D ‐(+)‐glucose, D ‐(+)‐mannose, methyl‐α‐D ‐glucopyranoside, methyl‐β‐D ‐galactopyranoside and methyl α‐D ‐mannopyranoside under neutral conditions was investigated by ¹H, ¹³C and ¹¹B NMR spectroscopy and gas chromatography–mass spectrometry (GC–MS) D ‐(+)‐Glucose and D ‐(+)‐mannose formed complexes where the boronates are attached to the 1,2:4,6‐ and 2,3:5,6‐positions of the furanose forms, respectively. On the other hand, the boronic acid binds to the 4,6‐positions of the two methyl derivatives of glucose and galactose. Methyl α‐D ‐mannopyranoside binds two boronates at the 2,3:4,6‐positions. ¹¹B NMR was used to show the ring size of the complexed sugars and the boronate. GC–MS confirmed the assignments. Copyright © 2003 John Wiley & Sons, Ltd.     

Copper‐Catalyzed Borylcupration of Allenylsilanes

A highly regio‐ and stereoselective copper‐catalyzed borylcupration of 1,2‐allenylsilanes affords an unexpected regioreversed allylic boronate bearing an extra C?Si bond at the 3‐position, with a thermodynamically disfavored Z geometry. Such stereodefined allylic boronates containing an extra alkenyl silane moiety are very useful organodimetallic reagents for organic synthesis.     

Ruthenium‐Catalyzed Multicomponent Reactions: Access to α‐Silyl‐β‐Hydroxy Vinylsilanes,Stereodefined 1,3‐Dienes,and Cyclohexenes

The synthesis of densly functionized α‐silyl‐β‐hydroxyl vinylsilanes via ruthenium‐catalyzed multicomponent reaction (MCR) is reported herein. Exceptionally high regio‐ and diastereoselectivity was achieved by employing an unprecedented hydrosilylation of bifunctional silyl‐propargyl boronates. The simple protocol, mild reaction conditions, and unique tolerability of this method make it a valuable tool for the synthesis of highly elaborated building blocks. The one‐pot synthesis of stereodefined olefins, the generation of a valuable cyclohexene building block through a four‐component MCR, and further functionalization in an abundance of diastereoselective reactions is disclosed herein.     

Silver(I)‐Catalyzed Diastereoselective Synthesis of anti‐1,2‐Hydroxyboronates

A catalytic protocol for the diastereoselective synthesis of anti‐1,2‐hydroxyboronates is described. The process provides access to secondary alkyl organoborons. The deborylative 1,2‐addition reactions of alkyl 1,1‐diborons proceed in the presence of a silver(I) salt with either KOtBu or nBuLi as an activator. The catalytic diastereoselective protocol can be extended to aryl, alkenyl, and alkyl aldehydes with up to 99:1 d.r.     

Palladium‐Catalyzed Heck‐Type Cross‐Couplings of Unactivated Alkyl Iodides

A palladium‐catalyzed, intermolecular Heck‐type coupling of alkyl iodides and alkenes is described. This process is successful with a variety of primary and secondary unactivated alkyl iodides as reaction partners, including those with hydrogen atoms in the β position. The mild catalytic conditions enable intermolecular C? C bond formations with a diverse set of alkyl iodides and alkenes, including substrates containing base‐ or nucleophile‐sensitive functionality.     

5‐Butyl‐4‐(4,4,5,5‐tetra­methyl‐1,3,2‐dioxaborolan‐2‐yl)‐3‐(2,4,6‐tri­methyl­phenyl)­isoxazole

A novel [3+2]‐cyclo­addition reaction of alkynyl­boronates and nitrile oxides gave the title compound, C₂₂H₃₂BNO₃, as a single regioisomer. The X‐ray crystal structure analysis of this compound shows two independent mol­ecules in the asymmetric unit, each with approximately coplanar isoxazole and boronate rings.