The enantioselective synthesis of cyclopropylzinc reagents has been achieved via a copper-catalyzed carbozincation of 3,3-disubstituted cyclopropenes with diorganozinc reagents. The obtained ...organozinc compounds can be easily functionalized with a broad range of electrophiles, including palladium-catalyzed cross-couplings, affording highly substituted cyclopropanes. The operationally simple procedure using very low quantities of a commercially available and inexpensive copper catalyst provides a new tool for the synthesis of highly enantioenriched cyclopropanes as single diastereoisomers.
The highly diastereo‐ and enantioselective formation of polysubstituted cyclopropanes was easily achieved through the asymmetric copper‐catalyzed carbomagnesiation reaction of nonfunctionalized ...cyclopropene derivatives. The carbometalated species generated in situ readily undergo C−C and C−X bond‐forming reactions with various electrophiles with complete retention of configuration.
Magnesiated: Diastereo‐ and enantiomerically enriched cyclopropylmagnesium halides were synthesized through the copper‐catalyzed addition of Grignard reagents across cyclopropenes. The carbometalated species generated in situ readily undergo C−C and C−X bond‐forming reactions with various electrophiles with complete retention of configuration.
Despite the accessibility of numerous alkynes through coupling or substitution reactions, the synthesis of trialkyl-substituted alkynes is still a major challenge. Within this context, we reexplored ...the electrophilic alkynyl substitution between tertiary aliphatic chlorides and silylated alkynes. We were able to demonstrate that this approach is significantly more general than originally demonstrated by Capozzi and even tolerates several functional groups. Furthermore, we report diastereoselective reactions which in some instances gave excellent diastereoselectivity (dr >95:5).
A new concise construction of trans-clerodane diterpenoids is reported in which oxacyclic and trans-hydronaphthalene fragments are coupled, and the critical C9-quaternary carbon stereocenter formed ...stereoselectively, by 1,6-addition of a tertiary cuprate or a tertiary carbon radical to β-vinylbutenolide. This strategy is specifically illustrated by total syntheses of (−)-solidagolactone (4), (−)-16-hydroxycleroda-3,13-dien-15,16-olide (5, PL3), and (−)-annonene (6).
The hydrochlorination of alkenes has been extensively studied in research and is commonly featured in organic chemistry textbooks as an exemplification of the Markovnikov rule. However, the ...application of this reaction is typically limited to specific alkenes, such as highly substituted ones, styrenes, or strained systems. Conversely, monosubstituted or 1,2-disubstituted alkenes do not readily react with HCl gas or solutions of HCl gas at practical rates. The challenges associated with hydrochlorination reactions for these "non-activated" alkenes have spurred considerable research efforts over the past 30 years, which constitute the primary focus of this review. The discussion begins with classical polar hydrochlorinations, followed by metal-promoted radical hydrochlorinations, and concludes with a brief overview of recent anti-Markovnikov hydrochlorinations.
In this report, we address the challenge of assigning diastereomers for methyl cyclohexanes, particularly those with quaternary centers, which remains nontrivial despite modern NMR techniques. By ...utilizing a HSQC NMR experiment to identify methyl-carbons coupled with a simple conformational analysis, we identified an effective and quite general method for assigning stereochemistry, even in cases where diastereomeric mixtures are inseparable.
TMS-substituted alkynes are versatile building blocks in organic synthesis. Traditional synthesis involves alkyne deprotonation and the reaction with TMSCl. Recently, TMS-acetylene has become an ...increasingly inexpensive bulk chemical, offering an attractive alternative to accessing TMS-substituted alkynes, especially when the alkyne is expensive or not commercially available. However, this route has been established with carcinogenic HMPA as a cosolvent. In this work, we disclose optimized conditions utilizing DMPU as a substitute for HMPA.
The hydrochlorination of alkenes with hydrogen chloride gas is typically limited to activated olefins. Herein, we present an innovative hydrochlorination approach utilizing hydrochloric acid within ...vigorously agitated solutions. Notably, the introduction of acetic acid was found to enhance the reaction rate. We substantiated the practicality of our method by conducting the hydrochlorination of styrene on a 1-mol scale with a 96% yield.
Herein, we report the first enantio- and diastereoselective addition of stereodefined vinyl organometallic reagents to cyclopropenes. The operationally simple tandem hydroalumination and ...copper-catalyzed vinylmetalation allows for the unique access of a diverse set of enantioenriched vinylcyclopropane derivatives.
The evolution of a convergent fragment-coupling strategy for the enantioselective total synthesis of trans-clerodane diterpenoids is described. The key bond construction is accomplished by ...1,6-addition of a trans-decalin tertiary radical with 4-vinylfuran-2-one. The tertiary radical is optimally generated from the hemioxalate salt of the corresponding tertiary alcohol upon activation by visible light and an Ir(III) photoredox catalyst. The enantioselective total synthesis of trans-clerodane diterpenoid 1 reported here was accomplished in seven steps from 3-methyl-2-cyclohexenone. The synthetic strategy described in this report allows a number of trans-clerodane diterpenoids to be synthesized in enantioselective fashion by synthetic sequences of 10 steps or less. This study illustrates a powerful tactic in organic synthesis in which a structurally complex target structure is disconnected at a quaternary carbon stereocenter to fragments of comparable complexity, which are united in the synthetic pathway by conjugate addition of a nucleophilic tertiary radical to a fragment harboring an electron-deficient C–C double bond.
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