Ligand‐Controlled Regiodivergent Enantioselective Rhodium‐Catalyzed Alkene Hydroboration

Abstract

Regiocontrol in the rhodium-catalyzed boration of vinyl arenes is typically dominated by the presence of the conjugated aryl substituent. However,s mall differences in TADDOL-derived chiral monophosphite ligands can override this effect and direct rhodium-catalyzed hydroboration of baryl and b-heteroaryl methylidenes by pinacolborane to selectively produce either chiral primary or tertiary borated products.T he regiodivergent behavior is coupled with enantiodivergent addition of the borane.T he nature of the TADDOL backbone substituents and that of the phosphite moiety function synergistically to direct the sense and extent of regioselectivity and enantioinduction. Tw enty substrates are shown to undergo eachr eaction mode with regioselectivity values reaching greater than 20:1 and enantiomer ratios reaching up to 98:2. Avariety of subsequent transformations illustrate the potential utility of each product.Theenantioselectivepreparationofchiralboronicestersisof current interest due to the synthetic utility of these compounds in adiverse set of stereospecific transformations [1] and the growing appreciation that boronic acid derivatives may hold significant potential in medicinal chemistry. [2] Considerable progress has been realized in the development of regioselective asymmetric hydroboration [3,4] and asymmetric borometallation [5] reactions,m ost of which exploit substrate control through the use of activated alkenes or directing groups.C atalysts that override inherent substrate bias to selectively produce either of two regioisomers offer greater synthetic utility.I na ddition to several recent examples of non-stereocontrolled borylative difunctionalizations through regiodivergent borocupration, [6] the ligand-controlled regiodivergent palladium-catalyzed hydroboration of terminal alkynes serves to illustrate the potential of this approach. Ojiha and Prabhu [7] reported abulky N-heterocyclic carbene ligand promotes regioselective boropalladation to deliver boron to the terminus;p rotonolysis leads to 1 (Figure 1). In contrast, tricyclohexylphosphine effects delivery of boron to the internal position leading to the regioisomeric product 2.Examples of chiral-catalyst-controlled regiodivergent and enantioselective reactions are less common. [8,9] Herein, we report that relatively modest structural changes to ac hiral TADDOL-derived monophosphite ligand results in as witch in both regioselectivity and the sense of enantioselectivity in the catalytic asymmetric hydroboration (CAHB) of b-aryl methylidene substrates 3 by pinacolborane (pinBH). This method provides access to either rhodium-catalyzed g-boration at the unsubstituted terminus to give the primary organoboronic ester 4 (si-face addition favored), [10] or bboration to give the tertiary organoboronic ester 5 (re-face addition favored) [11] by using ligands (R,R)-T1 a or (R,R)-T2 b,r espectively.To probe the influence of structural changes in the ligand on the g-tob-boration ratio (4/5)and the levels of asymmetric induction (re/si-face addition), as eries o...

Ligand‐Controlled Copper‐Catalyzed Regiodivergent Carbonylative Synthesis of α‐Amino Ketones and α‐Boryl Amides from Imines and Alkyl Iodides

“…[5] Based on the continues efforts from organic chemists, great successes have been made during the past decades. In particular, transitionmetal catalysts such as copper, [6] palladium, [7] and rhodium [8] have been extensively studied in this topic. Furthermore, ligands design provides more opportunities for regioselective transformations, which can affect the metallic complexs structural and electronic properties by the electronic and steric properties of the ligands.…”

Iridium‐Catalyzed Regiodivergent and Enantioselective Hydroalkynylation of Unactivated 1,1‐Disubstituted Alkenes

“…In addition, substituted styrenes were commonly used as the substrates in these hydrofunctionalization processes to facilitate the enantiotopic face discriminating event, thus adding structural constraints to the alkene substrates [2, 4, 6, 7] . Furthermore, with few exceptions, [5a,b, 6a] the catalytic hydrofunctionalizations place the functional group at the less hindered terminal position of 1,1‐disubstituted alkene [4–7] . Consequently, enantioselective hydrocarbofunctionalization of unactivated 1,1‐disubstituted alkene with access to both Markovnikov and anti ‐Markovnikov products remains an unsolved synthetic challenge to date (Scheme 1A) [8]…”

“…However, highly enantioselective hydrofunctionalizations of these substrates have been mostly limited to the reactions with reactive reagents such as catalytic hydrogenation [2,3] and hydroboration. [4,5] Intermolecular enantioselective CÀ C formation through hydrocarbofunctionalization of 1,1-disubstituted alkenes is particularly rare. [6][7][8] In addition, substituted styrenes were commonly used as the substrates in these hydrofunctionalization processes to facilitate the enantiotopic face discriminating event, thus adding structural constraints to the alkene substrates.…”

“…[2,4,6,7] Furthermore, with few exceptions, [5a,b, 6a] the catalytic hydrofunctionalizations place the functional group at the less hindered terminal position of 1,1-disubstituted alkene. [4][5][6][7] Consequently, enantioselective hydrocarbofunctionalization of unactivated 1,1-disubstituted alkene with access to both Markovnikov and anti-Markovnikov products remains an unsolved synthetic challenge to date (Scheme 1A). [8] As part of our continuing interest in directed asymmetric hydrofunctionalization of alkenes, [9] we have developed catalytic hydroalkynylations [10] of enamides, [11] where the regioselectivity could be modulated by the metal center or the ligand.…”

Ligand‐Controlled Copper‐Catalyzed Regiodivergent Carbonylative Synthesis of α‐Amino Ketones and α‐Boryl Amides from Imines and Alkyl Iodides

“…[5] Based on the continues efforts from organic chemists, great successes have been made during the past decades. In particular, transitionmetal catalysts such as copper, [6] palladium, [7] and rhodium [8] have been extensively studied in this topic. Furthermore, ligands design provides more opportunities for regioselective transformations, which can affect the metallic complexs structural and electronic properties by the electronic and steric properties of the ligands.…”