The stereocontrolled construction of C−C bonds remains one of the foremost challenges in organic synthesis. At the heart of any chemical synthesis of a natural product or designed small molecule is the need to orchestrate a series of chemical reactions to prepare and functionalize a carbon framework. The advent of transition-metal catalysis has provided chemists with a broad range of new tools to forge C−C bonds and has resulted in a paradigm shift in synthetic strategy planning. The impact of these methods was recognized with the awarding of the 2010 Nobel Prize in Chemistry to Richard Heck, Ei-ichi Negishi, and Akira Suzuki for their seminal contributions to the development of Pd-catalyzed cross-coupling.

Enantioselective and Enantiospecific Transition-Metal-Catalyzed Cross-Coupling Reactions of Organometallic Reagents To Construct C–C Bonds

The Suzuki-Miyaura reaction (SMR), involving the coupling of an organoboron reagent and an organic halide or pseudo-halide in the presence of a palladium or nickel catalyst and a base, has arguably become one of most utilized tools for the construction of a C-C bond This review intends to be general account of all types of catalytic systems, new coupling partners and applications, including the literature between September 2010 and December 2014

Recent developments in the Suzuki-Miyaura reaction: 2010-2014.

The cross-coupling of boronic acids and related derivatives with sp(2) electrophiles (the Suzuki-Miyaura reaction) is one of the most powerful C-C bond formation reactions in synthesis, with applications that span pharmaceuticals, agrochemicals and high-tech materials. Despite the breadth of its utility, the scope of this Nobel prize-winning reaction is rather limited when applied to aliphatic boronic esters. Primary organoboron reagents work well, but secondary and tertiary boronic esters do not (apart from a few specific and isolated examples). Through an alternative strategy, which does not involve using transition metals, we have discovered that enantioenriched secondary and tertiary boronic esters can be coupled to electron-rich aromatics with essentially complete enantiospecificity. As the enantioenriched boronic esters are easily accessible, this reaction should find considerable application, particularly in the pharmaceutical industry where there is growing awareness of the importance of, and greater clinical success in, creating biomolecules with three-dimensional architectures.

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Enantiospecific sp 2 – sp 3 coupling of secondary and tertiary boronic esters

ConspectusDeveloping new methods that enable the synthesis of new and complex molecules with complete control of their 3-D shape is central to the advancement of synthetic chemistry with applications spanning from medicine to materials. Our approach consists of the iterative combination of small building blocks through the use of boron chemistry to essentially “grow” molecules. This approach, which we term assembly-line synthesis (ALS), resembles the way that nature assembles natural products (e.g., the polyketide synthase machinery) and has the advantage that many structural variations can be easily introduced and the products can be evaluated in structural or biological contexts.Chiral boronic esters have been recognized as valuable building blocks due to their unique chemical properties. They are both chemically and configurationally stable, and they can be prepared with very high levels of enantioselectivity. Additionally they undergo a broad array of transformations that lead to the stereocontrolled ...

Lithiation-borylation methodology and its application in synthesis

Presented is the first enantioselective copper-catalyzed 1,6-conjugate addition of bis(pinacolato)diboron to para-quinone methides. The reaction proceeds with excellent yields and good to excellent enantioselectivities, and provides an attractive approach to the construction of optically active gem-diarylmehtine boronic esters. Additionally, the subsequent conversion of the derived potassium trifluoroborates into triarylmethanes with highly enantiospecificity was realized.

Copper‐Catalyzed Enantioselective 1,6‐Boration of para‐Quinone Methides and Efficient Transformation of gem‐Diarylmethine Boronates to Triarylmethanes

Asymmetric cross-coupling reactions in which stereo- chemistry-bearing CC bonds are created are still in their infancy. Considering the wealth of compounds that can be prepared by cross-coupling methodologies, and the impor- tance of synthetic methods leading to enantiomerically en- riched products, this is a surprising reality. Advances in this area have occurred in the past few years, in the realm of enantioselective or enantiospecific cross-couplings of chiral electrophiles. (1) In the area of cross-coupling of stereodefined nucleo- philes, Crudden originally reported the enantiospecific cross-coupling of chiral enantiomerically enriched benzylic boronic esters (Eq. (1)). (2, 3)

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Enantiospecific, Regioselective Cross-Coupling Reactions of Secondary Allylic Boronic Esters

The Suzuki-Miyaura cross-coupling of enantioenriched secondary allylic boronic esters occurs with high γ-regioselectivity and high retention of chirality, proceeding via γ-selective transmetalation and subsequent reductive elimination.

Emily LaBine

Papers

Enantiospecific, Regioselective Cross-Coupling Reactions of Secondary Allylic Boronic Esters

Enantiospecific, Regioselective Cross‐Coupling Reactions of Secondary Allylic Boronic Esters.