Enantioenriched secondary and tertiary alkyl pinacolboronic esters undergo enantiospecific deborylative alkynylation through a Zweifel-type alkenylation followed by a 1,2-elimination reaction. The process involves use of α-lithio vinyl bromide or vinyl carbamate species, for which application to Zweifel-type reactions has not previously been explored. The resulting functionalized 1,1-disubstituted alkenes undergo facile base-mediated elimination to generate terminal alkyne products in high yield and excellent levels of enantiospecificity over a wide range of pinacolboronic ester substrates. Furthermore, along with terminal alkynes, internal and silyl-protected alkynes can be formed by simply introducing a suitable carbon- or silicon-based electrophile after the base-mediated 1,2-elimination reaction.

Enantioenriched secondary and tertiary alkyl pinacolboronic esters undergo enantiospecific deborylative alkynylation through a Zweifel-type alkenylation followed by a 1,2-elimination reaction. The process involves use of α-lithio vinyl bromide or vinyl carbamate species, for which application to Zweifel-type reactions has not previously been explored. The resulting functionalized 1,1-disubstituted alkenes undergo facile base-mediated elimination to generate terminal alkyne products in high yield and excellent levels of enantiospecificity over a wide range of pinacolboronic ester substrates. Furthermore, along with terminal alkynes, internal and silyl-protected alkynes can be formed by simply introducing a suitable carbon- or silicon-based electrophile after the base-mediated 1,2-elimination reaction.

Tetrahydropyrans are common motifs in natural products and have now been constructed with high stereocontrol through a three-component allylboration-Prins reaction sequence. This methodology has been applied to a concise (13 steps) and efficient (14 % overall yield) synthesis of the macrolide (−)-clavosolide A. The synthesis also features an early stage glycosidation reaction to introduce the xylose moiety and a lithiation-borylation reaction to attach the cyclopropyl-containing side chain.

Tetrahydropyrans are common motifs in natural products and have now been constructed with high stereocontrol through a three-component allylboration-Prins reaction sequence. This methodology has been applied to a concise (13 steps) and efficient (14 % overall yield) synthesis of the macrolide (−)-clavosolide A. The synthesis also features an early stage glycosidation reaction to introduce the xylose moiety and a lithiation-borylation reaction to attach the cyclopropyl-containing side chain.

Using iterative lithiation–borylation homologations, the mycolactone toxin core has been synthesized in 13 steps and 17 % overall yield. The rapid build-up of molecular complexity, high convergence and high stereoselectivity are noteworthy features of this synthesis.

This Minireview highlights advances in the Suzuki–Miyaura cross-coupling of secondary boron reagents for the creation of CC bonds with control of stereochemistry. It also includes non-transition-metal coupling of secondary and tertiary boronic esters to electron-rich aromatics.

Lithiation/borylation methodology has been developed for the synthesis of acyclic quaternary-tertiary motifs with full control of relative and absolute stereochemistry, thus leading to all four possible isomers of a stereodiad. A novel intramolecular Zweifel-type olefination enabled acyclic stereocontrol to be transformed into cyclic stereocontrol. These key steps have been applied to the shortest enantioselective synthesis of (−)-filiformin to date (9 steps) with full stereocontrol.

Allylic pinacol boronic esters are stable toward 1,3-borotropic rearrangement. We developed a Pd^II-mediated isomerization process that gives di- or trisubstituted allylic boronic esters with high E selectivity. The combination of this method with lithiation–borylation enables the synthesis of carbon chains that bear 1,5-stereogenic centers. The utility of this method has been demonstrated in a formal synthesis of (+)-jasplakinolide.

Lithiation/borylation methodology has been developed for the synthesis of acyclic quaternary-tertiary motifs with full control of relative and absolute stereochemistry, thus leading to all four possible isomers of a stereodiad. A novel intramolecular Zweifel-type olefination enabled acyclic stereocontrol to be transformed into cyclic stereocontrol. These key steps have been applied to the shortest enantioselective synthesis of (−)-filiformin to date (9 steps) with full stereocontrol.

α,α-Disubstituted allylic pinacol boronic esters undergo highly selective allylborations of aldehydes to give tetrasubstituted homoallylic alcohols with exceptional levels of anti-Z-selectivity (>20:1). The scope of the reaction includes both acyclic and cyclic allylic boronic esters which lead to acyclic and exocyclic tetrasubstituted homoallylic alcohols. The use of β-borylated allylic boronic esters gave fully substituted alkenes bearing a boronic ester which underwent further cross-coupling enabling a highly modular and stereoselective approach to the synthesis of diaryl tetrasubstituted alkenes. Computational analysis revealed the origin of the remarkable selectivity observed.

The universal mating hormone α 1 of the virulent plant pathogen Phytophthora has been synthesized in 12 steps and 28 % overall yield. Key CC bond-forming steps involved the use of two lithiation/borylation reactions to couple together enantioenriched building blocks, one of which also set up the stereochemistry of the tertiary alcohol at C11. Detailed analysis showed that the diastereomeric purity of the target molecule was >91 %, the highest obtained to date.

3,3-Disubstituted allylic boronic esters are not sufficiently reactive to react with ketones and imines. However, they can be converted into the corresponding borinic esters by the sequential addition of nBuLi and TFAA. These reactive intermediates possess the perfect balance between reactivity and configurational stability. Their enhanced reactivity allows the highly selective allylation of both ketones and ketimines, and facile access to adjacent quaternary stereocenters with full stereocontrol. The versatility of the methodology is demonstrated in the construction of all possible stereoisomers of a quaternary-quaternary motif and by the allylation of the heterocycles, dihydroisoquinoline and indole.

The universal mating hormone α 1 of the virulent plant pathogen Phytophthora has been synthesized in 12 steps and 28 % overall yield. Key CC bond-forming steps involved the use of two lithiation/borylation reactions to couple together enantioenriched building blocks, one of which also set up the stereochemistry of the tertiary alcohol at C11. Detailed analysis showed that the diastereomeric purity of the target molecule was >91 %, the highest obtained to date.

α,α-Disubstituted allylic pinacol boronic esters undergo highly selective allylborations of aldehydes to give tetrasubstituted homoallylic alcohols with exceptional levels of anti-Z-selectivity (>20:1). The scope of the reaction includes both acyclic and cyclic allylic boronic esters which lead to acyclic and exocyclic tetrasubstituted homoallylic alcohols. The use of β-borylated allylic boronic esters gave fully substituted alkenes bearing a boronic ester which underwent further cross-coupling enabling a highly modular and stereoselective approach to the synthesis of diaryl tetrasubstituted alkenes. Computational analysis revealed the origin of the remarkable selectivity observed.

Allylic pinacol boronic esters are stable toward 1,3-borotropic rearrangement. We developed a Pd^II-mediated isomerization process that gives di- or trisubstituted allylic boronic esters with high E selectivity. The combination of this method with lithiation–borylation enables the synthesis of carbon chains that bear 1,5-stereogenic centers. The utility of this method has been demonstrated in a formal synthesis of (+)-jasplakinolide.

3,3-Disubstituted allylic boronic esters are not sufficiently reactive to react with ketones and imines. However, they can be converted into the corresponding borinic esters by the sequential addition of nBuLi and TFAA. These reactive intermediates possess the perfect balance between reactivity and configurational stability. Their enhanced reactivity allows the highly selective allylation of both ketones and ketimines, and facile access to adjacent quaternary stereocenters with full stereocontrol. The versatility of the methodology is demonstrated in the construction of all possible stereoisomers of a quaternary-quaternary motif and by the allylation of the heterocycles, dihydroisoquinoline and indole.

The effect of the nature of the N-protecting group on 1,2-amino alcohols in annulation reactions with diphenylvinylsulfonium triflate has been investigated. Although tosyl and sulfinamide groups give morpholines in high yields, the use of N-Cbz leads to a high-yielding synthesis of N-vinyloxazolidinones. The reactions were monitored by nanospray MS/MS, which revealed why reactions are successful and the fate of reactive intermediates in the unsuccessful reactions.

A versatile and simple method is reported for the synthesis of bicyclic epoxide and aziridinefused heterocycles (up to 98% yield, up to 96 : 4 er or up to 15 : 1 dr), using a tandem Michael addition/JohnsonCoreyChaykovsky annulation approach. A new chiral (2-bromoethyl)sulfonium reagent is described, based on an easily available chiral sulfide; it promotes or enhances stereoselectivity in the reaction.

1,2-Amino alcohols have been converted into morpholines by using sulfinamides as temporary protecting/activating groups on the amine. We have developed a procedure for the selective synthesis of monoprotected N-sulfinyl amino alcohols through a double sulfinylation/hydrolysis strategy. Following the reaction of the sulfinamides with bromoethyldiphenylsulfonium triflate, protected morpholines were obtained in high yields. Subsequent treatment with HCl liberated the morpholine hydrochloride salts. The usefulness of this high yielding and efficient methodology has been demonstrated in the formal synthesis of the antidepressant drug (S,S)-reboxetine.

Organoboron compounds are useful in asymmetric synthesis. We have developed an efficient methodology for the highly enantioselective synthesis of tertiary boronic esters from the corresponding secondary benzylic alcohols. Further stereospecific transformations of the boronic ester moiety are described including the preparation of tertiary alcohols, C-tertiary amines and tertiary arylalkanes. Several homologations of tertiary boronic esters have also been developed for the construction of quaternary stereocentres.

Organoboranes and boronic esters readily undergo nucleophilic addition, and if the nucleophile also bears an α-leaving group, 1,2-metallate rearrangement of the ate complex results. Through such a process a carbon chain can be extended, usually with high stereocontrol and this is the focus of this review. A chiral boronic ester (substrate control) can be used for stereocontrolled homologations with (dichloromethyl)lithium in the presence of ZnCl₂. Subsequent alkylation by an organometallic reagent also occurs with high levels of stereocontrol. Chiral lithiated carbanions (reagent control) can also be used for the reaction sequence with achiral boronic esters and boranes. Aryl-stabilized sulfur ylide derived chiral carbanions can be homologated with a range of boranes including vinyl boranes in good yield and high diastereo- and enantioselectivity. Lithiated alkyl chlorides react with boronic esters, again with high stereocontrol, but both sets of reactions are limited in scope. Chiral lithiated carbamates show the greatest substrate scope and react with both boronic esters and boranes with excellent enantioselectivity. Furthermore, iterative homologation with chiral lithiated carbamates allows carbon chains to be “grown” with control over relative and absolute stereochemistry. The factors responsible for stereocontrol are discussed. © 2009 The Japan Chemical Journal Forum and Wiley Periodicals, Inc. Chem Rec 9: 24–39; 2009: Published online in Wiley InterScience (www.interscience.wiley.com) DOI 10.1002/tcr.20168

Chiral nonracemic thiomorpholines have been synthesized in four to six steps from limonene or achiral alkenes using α-methylbenzylamine to control absolute stereochemistry. These aminosulfides have been used to generate sulfur ylides, which have been applied in the asymmetric epoxidation of aldehydes as easily recoverable catalysts. Excellent yields (up to 98 %), enantioselectivities (up to 97:3 e.r.), and diastereoselectivities (≥98:2 trans/cis) were achieved in these epoxidations and the sulfides were easily recovered in high yield (up to 97 %) by simple acid/base extraction.