Homologation and alkylation of boronic esters and boranes by 1,2‐metallate rearrangement of boron ate complexes

Thomas, Stephen P.; French, Rosalind M.; Jheengut, Vishal; Aggarwal, Varinder K.

doi:10.1002/tcr.20168

Cited by 183 publications

(68 citation statements)

References 38 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…84 This approach leverages the stereospecificity of the 1,2-metallate rearrangement of boronate complexes 85 to install both stereochemistry and functionality via iterative chain extension of boronic esters. In a one pot procedure, a boronic ester was subjected to a series of six homologations, installing three methylene spacer units as well as three methyl-bearing stereocenters derived from the requisite enantiomerically-pure lithiated benzoates.…”

Section: Many Customized Iterative Synthesis Methods Have Already Beementioning

confidence: 99%

Towards the generalized iterative synthesis of small molecules

2018

View full text Add to dashboard Cite

Small molecules have extensive untapped potential to benefit society, but access to this potential is too often restricted by limitations inherent to the customized approach currently used to synthesize this class of chemical matter. In contrast, the “building block approach”, i.e., generalized iterative assembly of interchangeable parts, has now proven to be a highly efficient and flexible way to construct things ranging all the way from skyscrapers to macromolecules to artificial intelligence algorithms. The structural redundancy found in many small molecules suggests that they possess a similar capacity for generalized building block-based construction. It is also encouraging that many customized iterative synthesis methods have been developed that improve access to specific classes of small molecules. There has also been substantial recent progress toward the iterative assembly of many different types of small molecules, including complex natural products, pharmaceuticals, biological probes, and materials, using common building blocks and coupling chemistry. Collectively, these advances suggest that a generalized building block approach for small molecule synthesis may be within reach.

show abstract

Section: Many Customized Iterative Synthesis Methods Have Already Beementioning

confidence: 99%

Towards the generalized iterative synthesis of small molecules

2018

View full text Add to dashboard Cite

show abstract

“…The stereoelectronic requirements of the metallate shift dictate an antiperiplanar arrangement of the migrating carbon atom (R) and the leaving group such that the overall process is stereoretentive at R, but stereoinvertive at A (8). These processes are common (9) for transformations where the “A” group is a carbon, nitrogen, or oxygen atom, and less common but still established for sulfur and phosphorus (10,11). Because of the stereospecific nature of the above-described processes, stereoselectivity in metallate shifts is generally subject to substrate control (12) though Jadhav and Man reported an example with selectivity dictated by a chiral catalyst (13).…”

mentioning

confidence: 99%

Catalytic conjunctive cross-coupling enabled by metal-induced metallate rearrangement

Zhang

Lovinger

Edelstein

et al. 2016

Science

285

110

View full text Add to dashboard Cite

Transition metal catalysis plays a central role in contemporary organic synthesis. Considering the tremendously broad array of transition-metal-catalyzed transformations, it is remarkable that the underlying elementary reaction steps are relatively few in number. Here we describe an alternative to the organometallic transmetallation step that is common in many metal-catalyzed reactions such as Suzuki-Miyaura coupling. Specifically, we demonstrate that vinyl boronic ester ate complexes, prepared by combining organoboronates and organolithium reagents, engage in Pd-induced metallate rearrangement wherein 1,2-migration of an alkyl or aryl group from boron to the vinyl α-carbon occurs concomitantly with C-Pd σ-bond formation. This elementary reaction enables a powerful cross-coupling reaction in which a chiral palladium catalyst merges three simple starting materials – an organolithium, an organoboronic ester, and an organotriflate – into chiral organoboronic esters with high enantioselectivity.

show abstract

“…

The creation of quaternary stereogenic centers with high enantioselectivity is challenging, in part, because of the high steric repulsion between the substituents on the carbon center that is generated during construction. [3] However, whilst the homologation reaction may seemingly appear to be a straight forward extension of the literature it should be noted that hindered tertiary boranes (e.g., thexyl) have often been employed as nonmigrating groups in homologations of boranes, [4] and examples of related transformations of tertiary boronic esters are rare. [1] However, whilst in many cases high e.r.

…”

mentioning

confidence: 99%

Enantioselective Construction of Quaternary Stereogenic Centers from Tertiary Boronic Esters: Methodology and Applications

et al. 2011

Self Cite

View full text Add to dashboard Cite

The creation of quaternary stereogenic centers with high enantioselectivity is challenging, in part, because of the high steric repulsion between the substituents on the carbon center that is generated during construction. Nevertheless, significant progress has been made towards this goal in recent years, even in conformationally flexible acyclic systems.[1] However, whilst in many cases high e.r. values have been achieved, the selectivities are invariably substrate-dependent.We have approached this problem from a different perspective and considered the possibility of employing stereospecific homologations of tertiary boronic esters 1. Such boronic esters can be easily prepared from the corresponding secondary alcohols with very high e.r. values by using the methodology developed by our group, [2] or alternatively, by borylation of allylic carbonates/Michael acceptors reported by Hoveyda and co-workers (Scheme 1).[3] However, whilst the homologation reaction may seemingly appear to be a straight forward extension of the literature it should be noted that hindered tertiary boranes (e.g., thexyl) have often been employed as nonmigrating groups in homologations of boranes, [4] and examples of related transformations of tertiary boronic esters are rare. [5,6] Furthermore, extending methodology from secondary to tertiary substrates is rarely straightforward as the extra steric demand often results in lower selectivity or alternative reaction pathways being followed.[7] Herein we describe our success in creating quaternary stereogenic centers with very high e.r. values and with a range of versatile functional groups; the subsequent application of the methodology in synthesis is also presented.We began our studies using the tertiary boronic ester 2 a which was subjected to standard Matteson homologation conditions [6] using chloromethyl lithium [6b] at low temperature. However, whilst the homologated alcohol product was obtained after oxidation in reasonable yield, almost 20 % of the oxidation product 4, seemingly derived from the starting material 2 a, was also isolated even when a large excess (4.0 equiv) of LiCH 2 Cl was employed (Scheme 2).Analysis of the reaction by 11 B NMR spectroscopy prior to oxidation revealed that in addition to the signal of desired boronic ester 5 at d = 32 ppm, a new peak at d = 49 ppm was observed, which is indicative of the presence of borinic ester 6.[8] This ester must have formed from the unexpected migration of the oxygen substituent [9] instead of the normally favored carbon migration, presumably as a consequence of the very hindered nature of the boronic ester. We reasoned that using a bulkier and less polar leaving group (smaller dipole moment) would favor the conformation required for C migration and therefore explored LiCH 2 Br as an alternative reagent.[10] Making this simple modification resulted in an improved yield of the desired homologated product (83 % yield) with only about 5 % of the product derived from O migration (Scheme 2).This reagent was applied to a series of ...

show abstract

Homologation and alkylation of boronic esters and boranes by 1,2‐metallate rearrangement of boron ate complexes

Cited by 183 publications

References 38 publications

Towards the generalized iterative synthesis of small molecules

Towards the generalized iterative synthesis of small molecules

Catalytic conjunctive cross-coupling enabled by metal-induced metallate rearrangement

Enantioselective Construction of Quaternary Stereogenic Centers from Tertiary Boronic Esters: Methodology and Applications

Contact Info

Product

Resources

About