Abstract:The rhodium‐catalyzed 1,4‐addition of organoboron reagents to electron‐deficient alkenes is a versatile method for the enantioselective construction of carbon–carbon bonds. The scope of these reactions is broad, and alkenes activated by adjacent carbonyls, imines, nitriles, phosphonyl groups, nitro groups, sulfonyl groups, C=N‐containing aromatic heterocycles, electron‐deficient arenes, or boryl groups are effective substrates. Regarding the pronucleophilic component, aryl‐, heteroaryl‐, and alkenylboron reage… Show more
“…However, without recourse to harsh bases, classical deprotonation strategies are largely limited to stabilized nucleophiles bearing moderate to strong electron-withdrawing groups (e.g., ketones and 1,3-dicarbonyl compounds) . Lewis acid catalysis has been employed to expand the scope of Michael addition to less acidic pronucleophiles (e.g., simple esters and nitriles), while the use of preformed organometallic reagents and stable enol equivalents has further broadened the scope of 1,4-addition chemistry to nucleophiles that would be difficult to generate selectively by in situ deprotonation. However, the need for prefunctionalization steps reduces the attractiveness and practicality of protocols that call for preformed nucleophiles, particularly if the requisite organometallic reagent is complex or functional group-rich.…”
The iron-catalyzed coupling of alkenes and enones through allylic C(sp 3 )−H functionalization is reported. This redoxneutral process employs a cyclopentadienyliron(II) dicarbonyl catalyst and simple alkene substrates to generate catalytic allyliron intermediates for 1,4-addition to chalcones and other conjugated enones. The use of 2,4,6-collidine as the base and a combination of triisopropylsilyl triflate and LiNTf 2 as Lewis acids was found to facilitate this transformation under mild, functional group-tolerant conditions. Both electronically unactivated alkenes as well as allylbenzene derivatives could be employed as pronucleophilic coupling partners, as could a range of enones bearing electronically varied substituents.
“…However, without recourse to harsh bases, classical deprotonation strategies are largely limited to stabilized nucleophiles bearing moderate to strong electron-withdrawing groups (e.g., ketones and 1,3-dicarbonyl compounds) . Lewis acid catalysis has been employed to expand the scope of Michael addition to less acidic pronucleophiles (e.g., simple esters and nitriles), while the use of preformed organometallic reagents and stable enol equivalents has further broadened the scope of 1,4-addition chemistry to nucleophiles that would be difficult to generate selectively by in situ deprotonation. However, the need for prefunctionalization steps reduces the attractiveness and practicality of protocols that call for preformed nucleophiles, particularly if the requisite organometallic reagent is complex or functional group-rich.…”
The iron-catalyzed coupling of alkenes and enones through allylic C(sp 3 )−H functionalization is reported. This redoxneutral process employs a cyclopentadienyliron(II) dicarbonyl catalyst and simple alkene substrates to generate catalytic allyliron intermediates for 1,4-addition to chalcones and other conjugated enones. The use of 2,4,6-collidine as the base and a combination of triisopropylsilyl triflate and LiNTf 2 as Lewis acids was found to facilitate this transformation under mild, functional group-tolerant conditions. Both electronically unactivated alkenes as well as allylbenzene derivatives could be employed as pronucleophilic coupling partners, as could a range of enones bearing electronically varied substituents.
“…The rich chemistries afforded by homogeneous Rh(I) catalysis have been studied within academia for decades and more recently have attracted attention within process research and development in the fine chemical industry. For example, Rh(I)-catalyzed hydrogenation has been a popular transformation on process scale, and other industrial applications include Rh(I)-catalyzed hydroformylation, conjugate addition, C–H functionalization, and transfer hydrogenation …”
Rhodium
is a critical transition metal in catalyzing chemical transformations
in both academia and industry. Over the years Rh(I)-catalyzed chemical
transformations such as hydroformylation, conjugate addition, C–H
functionalization, and transfer hydrogenation have found broad application
in the fine chemical industry. However, Rh(I) precatalyst complexes
with weakly coordinated ligands are inherently unstable and thermally
decompose to generate a variety of noncondensable, flammable, and/or
toxic products. Exposure of [Rh(ethylene)2Cl]2 to air promotes its thermal decomposition at temperatures as low
as ∼44 °C by differential scanning calorimetry (DSC) analysis,
thus significantly increasing the thermal instability hazards and
leading to high potential for fire or explosion risk. A thermokinetic
model predicts that the adiabatic induction time of [Rh(ethylene)2Cl]2 in the presence of air is only 3.1 days at
25 °C and 24 h at 31.7 °C, indicating that exposure of [Rh(ethylene)2Cl]2 to air significantly increases the thermal
instability hazards of this catalyst. DSC screening of a variety of
other Rh(I) precatalyst complexes with loosely coordinated ligands
revealed similar thermal instability hazards, and these hazards were
significantly increased when the complexes were evaluated with an
air headspace compared with those under an inert atmosphere. We expect
this contribution to promote awareness of these potential safety hazards
within the wider scientific community. Scientists should understand
the thermal instability hazards of their specific Rh(I) precatalyst
complexes and employ safer measures, for example, inert atmosphere
and safe temperature windows, to prevent related incidents when handling
such Rh(I) precatalyst complexes during their research, especially
on scale.
“…The present asymmetric reaction proceeded as well with a bisphosphine ligand, ( R )-binap, although the enantioselectivity was lower (entry 9). The reaction in dioxane/H 2 O, which is a homogeneous solvent system commonly used for rhodium-catalyzed arylation reactions, − gave 3aa with slightly lower enantioselectivity (93% ee) (entry 10). At 30 °C, the reaction was slow, giving 48% yield of 3aa , together with recovery of 39% of 1a as a racemic mixture (entry 11).…”
mentioning
confidence: 99%
“…Dynamic kinetic resolution (DKR) in asymmetric synthesis has been proven to be an ideal method of preparing enantioenriched products from racemic substrates, and it consists of racemization of a chiral substrate and kinetic resolution of the racemized substrate. − Recently, Johnson reported a novel DKR in the rhodium-catalyzed asymmetric arylation of achiral γ-alkyl α-angelica lactones, giving β,γ-disubstituted γ-butyrolactones with high enantio- and trans-selectivity, where the racemization of chiral α,β-unsaturated lactone takes place through its equilibration with an achiral alkenyl ester (Scheme a). − Here, we report a lactam version of the same type of DKR. In addition to the high synthetic utility of the arylated lactam products, the present reaction has an advantage over the lactone version in that an appropriate choice of the substituents on the lactam nitrogen would give us a chance to attain high efficiency in the DKR by controlling the racemization rate as well as the reactivity and enantioselectivity at the rhodium-catalyzed arylation. − We found that the use of Boc (COO t -Bu) as a protecting group on the lactam nitrogen together with a chiral diene ligand L1a on the rhodium catalyst enabled the DKR in the asymmetric conjugate arylation/alkenylation of γ-substituted α,β-unsaturated γ-lactams ( rac - 1 ) to proceed with high efficiency in all aspects (Scheme b).…”
The reaction of racemic γ-substituted α,β-unsaturated
γ-lactams rac-1 with arylboron
reagents 2 in the presence of a chiral diene L1a–rhodium catalyst under basic conditions (3.0 equiv of NEt3) gave high yields of β,γ-disubstituted trans-γ-lactams 3 with both high diastereo-
and enantioselectivity. Fast racemization of 1 by way
of a dienolate generated with the base followed by kinetic resolution
of 1 with the chiral rhodium catalyst realized this highly
efficient dynamic kinetic resolution. The synthetic utility of the
present method is demonstrated by the synthesis of key intermediates
to biologically active compounds.
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