17 research outputs found
SmI<sub>2</sub>-Mediated Coupling of Nitrones and <i>tert</i>-Butanesulfinyl Imines with Allenoates: Synthesis of β-Methylenyl-γ-lactams and Tetramic Acids
Nitrones and <i>tert</i>-butanesulfinyl imines undergo conjugate addition to alkyl allenoates under SmI<sub>2</sub>-mediated reductive coupling conditions to produce novel β-methylenyl-substituted γ-amino esters. The latter were readily transformed into the corresponding β-methylenyl-γ-lactams by simple zinc reduction (<i>N</i>-hydroxy amines) or by acid hydrolysis (sulfinamides). The diastereoselective preparation of various β-methylenyl-γ-lactams offers a route to tetramic acids, the key structural features of an important class of bioactive natural products
Metal-Free Intermolecular Coupling of Arenes with Secondary Amides: Chemoselective Synthesis of Aromatic Ketimines and Ketones, and <i>N</i>‑Deacylation of Secondary Amides
The direct transformation of common
secondary amides into aromatic
ketimines and aromatic ketones with C–C bond formation is described.
The reaction can also be used for <i>N</i>-deacylation of
secondary amides to release amines. This method consists of <i>in situ</i> amide activation with triflic anhydride and intermolecular
capture of the resulting highly electrophilic nitrilium intermediate
with an arene. The reaction is applicable to various kinds of secondary
amides (electrophiles), but only electron-rich and moderately electron-rich
arenes can be used as nucleophiles. Thanks to the use of bench stable
arenes instead of reactive and basic organometallics as nucleophiles,
the reaction proceeded with high chemoselectivity at the secondary
amido group in the presence of a series of sensitive functional groups
such as aldehyde, ketone, ester, cyano, nitro, and tertiary amido
groups. The reaction can be viewed as a Friedel–Crafts-type
reaction using secondary amides as acylating agents or as an intermolecular
version of the Bischler–Napieralski reaction
Mild Metal-Free Hydrosilylation of Secondary Amides to Amines
The
combination of amide activation by Tf<sub>2</sub>O with BÂ(C<sub>6</sub>F<sub>5</sub>)<sub>3</sub>-catalyzed hydrosilylation with
TMDS constitutes a method for the one-pot reduction of secondary amides
to amines under mild conditions. The method displays a broad applicability
for the reduction of many types of substrates, and shows good compatibility
and excellent chemoselectivity for many sensitive functional groups.
Reductions of a multifunctionalized α,β-unsaturated amide
obtained from another synthetic methodology, and a C–H functionalization
product produced the corresponding amines in good to excellent yield.
Chemoselective reduction of enantiomeric pure (ee >99%) tetrahydro-5-oxo-2-furaneamides
yielded 5-(aminomethyl)Âdihydrofuran-2Â(3<i>H</i>)-ones in
a racemization-free manner. The latter were converted in one pot to <i>N</i>-protected 5-hydroxypiperidin-2-ones, which are building
blocks for the synthesis of many natural products. Further elaboration
of an intermediate led to a concise four-step synthesis of (−)-<i>epi</i>-pseudoconhydrine
One-Pot Reductive 1,3-Dipolar Cycloaddition of Secondary Amides: A Two-Step Transformation of Primary Amides
The
one-pot reductive 1,3-dipolar cycloaddition of secondary aromatic <i>N</i>-(trimethylsilylmethyl)Âamides with reactive dipolarophiles
is reported. The method relies on the in situ generation of nonstabilized
NH azomethine ylide dipoles via amide activation with triflic anhydride,
partial reduction with 1,1,3,3-tetramethyldisiloxane (TMDS), and desilylation
with cesium fluoride (CsF). Running under mild conditions, the reaction
tolerated several sensitive functional groups and provided cycloadducts
in 71–93% yields. The use of less reactive dipolarophile methyl
acrylate led to the cycloadduct in only 40% yield. A (<i>Z</i>) geometric intermediate of NH-azomethine 1,3-dipole was postulated
to account for the observed higher yields and higher <i>cis</i> diastereoselectivity for the substrates bearing an electron-withdrawing
group. This model features an unconventional cyclic transition state
via carbanion–aryl ring interaction. Because the starting secondary
amides can be prepared from common primary amides, the current method
also constitutes a two-step transformation of primary amides
General and Chemoselective Bisphosphonylation of Secondary and Tertiary Amides
With
Tf<sub>2</sub>O as the activation reagent, a mild and general
method has been developed for the bisphosphonylation of both secondary
and tertiary amides. The protocol is highly efficient and chemoselective,
and it tolerates a number of sensitive functional groups such as cyano,
ester, and aldehyde groups
Asymmetric Total Synthesis and Absolute Configuration Determination of (−)-Verrupyrroloindoline
The first asymmetric total synthesis
of (−)-verrupyrroloindoline
(20% overall yield in 6 steps) is described. The short approach was
enabled by Buchwald’s CuÂ(II)-catalyzed asymmetric conjugate
reduction, DMDO-triggered one-pot four-step tandem reaction, and the
first amide-selective Ir-catalyzed direct reduction of β-carboethoxy
tertiary lactam. Along with the total synthesis, the absolute configuration
of natural verrupyrroloindoline was determined as 7<i>R</i>,10<i>R</i>,11<i>R</i>
Enantioselective Total Syntheses of (−)-FR901483 and (+)-8-<i>epi</i>-FR901483
The enantioselective total syntheses of the potent immunosuppressant
FR901483 (<b>1</b>) and its 8-epimer (<b>47</b>) have
been accomplished. Our approach features the use of building block <b>6</b> as the chiron, the application of the one-pot amide reductive
bis-alkylation method to construct the chiral aza-quaternary center
(dr = 9:1), regio- and diastereoselective intramolecular aldol reaction
to build the bridged ring, and RCM to form the 3-pyrrolin-2-one ring
A Formal Enantioselective Total Synthesis of FR901483
A formal enantioselective total synthesis of the potent immunosuppressant FR901483 (<b>1</b>) has been accomplished. Our approach features the use of chiron <b>6</b> as the starting material, the application of the one-pot amide reductive bisalkylation method to construct the chiral aza-quaternary center (dr = 9:1), regio- and diastereoselective intramolecular aldol reaction to build the bridged ring, and ring closing metathesis to form the 3-pyrrolin-2-one ring
SmI<sub>2</sub>‑Mediated Intermolecular Coupling of γ‑Lactam <i>N</i>‑α-Radicals with Activated Alkenes: Asymmetric Synthesis of 11-Hydroxylated Analogues of the Lead Compounds CP-734432 and PF-04475270
We report, for the first time, the synthesis of 8-aza-analogues
of PGE<sub>2</sub>. The SmI<sub>2</sub>-mediated cross coupling reactions
of γ-lactam-hemiaminal <b>9</b>, lactam 2-pyridyl sulfide <b>17</b>, and lactam 2-pyridyl sulfone <b>18</b> with activated
alkenes/alkyne were first developed, giving the corresponding γ-lactams
in 49–78%, 45–75%, and 75–90%, respectively.
The reactions of lactam 2-pyridyl sulfide and 2-pyridyl sulfone proceeded
with ≥12:1 <i>trans</i>-diastereoselectivities. This
represents the first intermolecular coupling reaction of the γ-lactam <i>N</i>-α-alkyl radicals of types <b>B</b>, <b>B1</b>, and <b>B2</b> with activated alkenes. Two radical-based
mechanisms were suggested. The asymmetric synthesis of the 11-hydroxylated
analogue of the highly selective EP<sub>4</sub> receptor agonist PF-04475270
(<b>30</b>), the 11-hydroxylated analogue of ocular hypotensive
CP-734432 (<b>31</b>), compounds <b>35</b> and <b>36</b> have been achieved on the basis of this method
SmI<sub>2</sub>‑Mediated Intermolecular Coupling of γ‑Lactam <i>N</i>‑α-Radicals with Activated Alkenes: Asymmetric Synthesis of 11-Hydroxylated Analogues of the Lead Compounds CP-734432 and PF-04475270
We report, for the first time, the synthesis of 8-aza-analogues
of PGE<sub>2</sub>. The SmI<sub>2</sub>-mediated cross coupling reactions
of γ-lactam-hemiaminal <b>9</b>, lactam 2-pyridyl sulfide <b>17</b>, and lactam 2-pyridyl sulfone <b>18</b> with activated
alkenes/alkyne were first developed, giving the corresponding γ-lactams
in 49–78%, 45–75%, and 75–90%, respectively.
The reactions of lactam 2-pyridyl sulfide and 2-pyridyl sulfone proceeded
with ≥12:1 <i>trans</i>-diastereoselectivities. This
represents the first intermolecular coupling reaction of the γ-lactam <i>N</i>-α-alkyl radicals of types <b>B</b>, <b>B1</b>, and <b>B2</b> with activated alkenes. Two radical-based
mechanisms were suggested. The asymmetric synthesis of the 11-hydroxylated
analogue of the highly selective EP<sub>4</sub> receptor agonist PF-04475270
(<b>30</b>), the 11-hydroxylated analogue of ocular hypotensive
CP-734432 (<b>31</b>), compounds <b>35</b> and <b>36</b> have been achieved on the basis of this method