8 research outputs found
Rhodium/Chiral Diene Complexes in the Catalytic Asymmetric Arylation of β‑Pyrazol-1-yl Acrylates
The asymmetric conjugate
addition of arylboronic acids to substituted
and unsubstituted β-pyrazol-1-yl (<i>E</i>)-<i>tert</i>-butyl acrylates <b>4</b> catalyzed by 5 mol %
of the RhÂ(I)/diene <b>2a</b> catalyst provided the corresponding
addition products in 44–98% yield and 91–>99.5% ee.
The method was applied to the formal synthesis of (3<i>S</i>)-3-aryl-3-(pyrazol-1-yl)Âpropanoic acid <b>1b</b> with agonistic
activity toward the human GPR40 G-protein coupled receptor
Rh-Catalyzed Enantioselective Allylation of <i>N</i>‑Tosyl- and <i>N</i>‑Nosylaldimines: Total Synthesis of (−)-Crispine A
The
unprecedented development of asymmetric Rh-catalyzed 1,2-allylation
of <i>N</i>-Ts- and <i>N</i>-Ns-aldimines is achieved.
This protocol utilizes potassium allyltrifluoroborates and various
aldimines to generate enantioenriched homoallylic amines in the presence
of 3.0 mol % of RhÂ(I)/<b>L1b</b> catalyst with up to 90% yield,
98% ee (R = H), and 10:1 diastereoselectivity (R = Me or Ph), yielding
the same major diastereomer when using potassium (<i>E</i>)- and (<i>Z</i>)-crotyltrifluoroborate. Its synthetic
utility is also illustrated in the total synthesis of (−)-crispine
A
Rh(I)-Catalyzed 1,4-Conjugate Addition of Alkenylboronic Acids to a Cyclopentenone Useful for the Synthesis of Prostaglandins
An efficient and <i>trans</i>-diastereoselective RhÂ(I)-catalyzed
1,4-conjugate addition reaction of alkenylboronic acids and a homochiral
(<i>R</i>)-4-silyloxycyclopentenone useful for the synthesis
of derivatives of prostaglandins E and F is described for the first
time. The reaction functions under mild conditions and is particularly
rapid (≤6 h) under low power (50 W) microwave irradiation at
30 °C in MeOH in the presence of a catalytic amount of KOH. Under
these conditions, 3 mol % of [RhClÂ(COD)]<sub>2</sub> is typically
required to produce high yields. The method also functions without
microwave irradiation at 3 °C in the presence of a stoichiometric
amount of KOH. Under these conditions, only 1.5 mol % of [RhClÂ(COD)]<sub>2</sub> is needed, but the reaction is considerably slower. The method
accepts a range of aryl- and alkyl-substituted alkenylboronic acids,
and its utility has been demonstrated by the synthesis of PGF<sub>2α</sub> (dinoprost) and tafluprost
Rhodium-Catalyzed Asymmetric Addition of Arylboronic Acids to β‑Nitroolefins: Formal Synthesis of (<i>S</i>)‑SKF 38393
An efficient enantioselective addition of an array of arylboronic
acids to various β-nitrostyrenes catalyzed by a novel and reactive
rhodium–diene catalyst (S/C up to 1000) was developed, providing
β,β-diarylnitroethanes in good to high yields (62–99%)
with excellent enantioselectivities (85–97% ee). The method
was extended to 2-heteroarylnitroolefins and 2-alkylnitroolefins similarly
providing the desired products with high enantioselectivities and
yields. The usefulness of this method was demonstrated in the formal
synthesis of the enantiomer of the dopamine receptor agonist and antagonist,
SKF 38393
β‑Selective <i>C</i>‑Arylation of Diisobutylaluminum Hydride Modified 1,6-Anhydroglucose: Synthesis of Canagliflozin without Recourse to Conventional Protecting Groups
The β-selective phenylation
of benzyl and boronate protected
1,6-anhydroglucose and the direct phenylation of unprotected 1,6-anhydroglucose
(<b>10</b>), pretreated with <i>i</i>-Bu<sub>2</sub>AlH, <i>i</i>-Bu<sub>3</sub>Al, Et<sub>3</sub>Al, Me<sub>3</sub>Al, or <i>n</i>-octyl<sub>3</sub>Al, with triphenylalane
or arylÂ(chloro)Âalanes is reported. The utility of the unprotected
version of the method is demonstrated by the synthesis of the SGLT2
inhibitor, canagliflozin (<b>1a</b>), from commercially available <b>10</b> in one C–C bond-forming step. This approach circumvents
the need for conventional protecting groups, and therefore no formal
protection and deprotection steps are required
β‑Selective <i>C</i>‑Arylation of Silyl Protected 1,6-Anhydroglucose with Arylalanes: The Synthesis of SGLT2 Inhibitors
The stereoselective arylation of
hydroxy protected 1,6-anhydro-β-d-glucose with arylalanes
to provide β-<i>C</i>-arylglucosides is reported.
Modification of triarylalanes, Ar<sub>3</sub>Al, with strong Brønsted
acids (HX) or AlCl<sub>3</sub> produced more reactive arylating agents,
Ar<sub>2</sub>AlX, while
the incorporation of alkyl dummy ligands into the arylating agents
was also viable. Me<sub>3</sub>Al and <i>i</i>-Bu<sub>2</sub>AlH were found useful in the <i>in situ</i> blocking of
the C3-hydroxyl group of 2,4-di-<i>O</i>-TBDPS protected
1,6-anhydroglucose. The utility of the method was demonstrated by
the synthesis of the SGLT2 inhibitor, canagliflozin
Enantioselective and Rapid Rh-Catalyzed Arylation of <i>N</i>‑Tosyl- and <i>N</i>‑Nosylaldimines in Methanol
Enantiomerically
enriched tosyl-protected diarylmethylamines were
rapidly prepared by the asymmetric addition of arylboronic acids to <i>N</i>-tosylaldimines under mild conditions in the presence of
a catalyst prepared in situ from RhÂ(I) and a chiral diene ligand.
This methodology offers access to diarylmethylamines in good yields
with excellent chiral purity at room temperature using MeOH as a solvent
and NEt<sub>3</sub> as a base. Its synthetic utility was demonstrated
by the preparation of (S)-1-phenyl-1,2,3,4-tetrahydroisoquinoline
(<b>14</b>), an antagonist of the <i>N</i>-methyl-d-aspartate (NMDA) receptor
Enantioselective and Rapid Rh-Catalyzed Arylation of <i>N</i>‑Tosyl- and <i>N</i>‑Nosylaldimines in Methanol
Enantiomerically
enriched tosyl-protected diarylmethylamines were
rapidly prepared by the asymmetric addition of arylboronic acids to <i>N</i>-tosylaldimines under mild conditions in the presence of
a catalyst prepared in situ from RhÂ(I) and a chiral diene ligand.
This methodology offers access to diarylmethylamines in good yields
with excellent chiral purity at room temperature using MeOH as a solvent
and NEt<sub>3</sub> as a base. Its synthetic utility was demonstrated
by the preparation of (S)-1-phenyl-1,2,3,4-tetrahydroisoquinoline
(<b>14</b>), an antagonist of the <i>N</i>-methyl-d-aspartate (NMDA) receptor