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Abstract: Racemic cyclopropyl ketones undergo enantioselective rearrangement to deliver the corresponding dihydrofurans in the presence of a chiral phosphoric acid as the catalyst. The reaction involves activation of the donor‐acceptor cyclopropane substrate by the chiral Brønsted acid catalyst to promote the ring‐opening event, thus generating a carbocationic intermediate that subsequently undergoes cyclization. Computational studies and control experiments support this mechanistic pathway. [ABSTRACT FROM AUTHOR]

Frankincense (olibanum) is one of the oldest aromatic materials used by humans, but the key molecular constituents contributing to its characteristic odor remained unknown. Reported herein is the discovery that (1 S,2 S)-(+)- trans- and (1 S,2 R)-(+)- cis-2-octylcyclopropyl-1-carboxylic acids are highly potent and substantive odorants occurring in ppm amounts in all of the frankincense samples analyzed, even those showing radically different volatile compositions. These cyclopropyl-derived acids provide the very characteristic old churchlike endnote of the frankincense odor. [ABSTRACT FROM AUTHOR]

A highly efficient asymmetric ring-opening/cyclization/retro-Mannich reaction of cyclopropyl ketones with aryl 1,2-diamines has been realized using a chiral N, N′-dioxide/ScIII catalyst. Benzimidazoles containing chiral side chains were generated under mild reaction conditions in excellent outcomes (up to 99 % yield and 97 % ee). This method also provides efficient access to chiral benzimidazole-substituted amide and cycloheptene derivatives. [ABSTRACT FROM AUTHOR]

Hydrosilyl ethers, generated in situ by the dehydrogenative silylation of cyclopropylmethanols with diethylsilane, undergo asymmetric, intramolecular silylation of cyclopropyl C−H bonds in high yields and with high enantiomeric excesses in the presence of a rhodium catalyst derived from a rhodium precursor and the bisphosphine ( S)-DTBM-SEGPHOS. The resulting enantioenriched oxasilolanes are suitable substrates for the Tamao-Fleming oxidation to form cyclopropanols with conservation of the ee value from the C−H silylation. Preliminary mechanistic data suggest that C−H cleavage is likely to be the turnover-limiting and enantioselectivity-determining step. [ABSTRACT FROM AUTHOR]

A novel formal [3+2] cycloaddition of cyclopropylacetals and aldehydes was developed, and the resulting trisubstituted tetrahydrofurans display three new chiral centers formed with highly diastereoselectivity. This method is stereocomplementary to most previously reported cycloadditions of malonate diesters, relies on the transient generation of cyclopropyl oxocarbenium ions, proceeds under mild conditions, and is based on the concept of temporary activation of an otherwise inert protecting group. [ABSTRACT FROM AUTHOR]

Tetrahydropyrans are common motifs in natural products and have now been constructed with high stereocontrol through a three-component allylboration-Prins reaction sequence. This methodology has been applied to a concise (13 steps) and efficient (14 % overall yield) synthesis of the macrolide (−)-clavosolide A. The synthesis also features an early stage glycosidation reaction to introduce the xylose moiety and a lithiation-borylation reaction to attach the cyclopropyl-containing side chain. [ABSTRACT FROM AUTHOR]

The combined regio- and stereoselective carbometalation of cyclopropenyl amides, followed by the addition of an acyl silane, led to the formation of polysubstituted cyclopropyl derivatives as unique diastereoisomers. Upon warming of the reaction mixture to room temperature, a Brook rearrangement proceeded with inversion of configuration to provide ready access to δ-ketoamides possessing a quaternary carbon center with high enantiomeric ratios through selective C¢C bond cleavage of the ring. [ABSTRACT FROM AUTHOR]

A highly efficient asymmetric ring-opening reaction of cyclopropyl ketones with a broad range of thiols, alcohols and carboxylic acids has been first realized by using a chiral N, N′-dioxide-scandium(III) complex as catalyst. The corresponding sulfides, ethers, and esters were obtained in up to 99 % yield and 95 % ee. This is also the first example of one catalytic system working for the ring-opening reaction of donor-acceptor cyclopropanes with three different nucleophiles, let alone in an asymmetric version. [ABSTRACT FROM AUTHOR]

Many 1,3-azoles and thiophenes are directly cyclopropylated in the presence of a simple palladium catalyst. The relative configuration on the three-membered rings is retained in the products. Thus, the cyclopropyl-halide bond undergoes concerted oxidative addition to palladium(0) and cyclopropyl radicals are not involved in the productive pathway. [ABSTRACT FROM AUTHOR]

Chloroacetic acid promotes an efficient and diastereoselective intramolecular cascade reaction of electron-deficient ynenones to deliver products featuring a 2,3,5-trisubstituted furan bearing a fused cyclopropyl substituent at the 5-position. Synthetically relevant polycyclic building blocks featuring rings of various sizes and heteroatoms have been synthesized in high yield using this mild acid-catalyzed reaction. [ABSTRACT FROM AUTHOR]

The ergot alkaloids, a class of fungal-derived natural products with important biological activities, are derived from a common intermediate, chanoclavine-I, which is elaborated into a set of diverse structures. Herein we report the discovery of the biosynthetic pathway of cycloclavine, a complex ergot alkaloid containing a cyclopropyl moiety. We used a yeast-based expression platform along with in vitro biochemical experiments to identify the enzyme that catalyzes a rearrangement of the chanoclavine-I intermediate to form a cyclopropyl moiety. The resulting compound, cycloclavine, was produced in yeast at titers of >500 mg L−1, thus demonstrating the feasibility of the heterologous expression of these complex alkaloids. [ABSTRACT FROM AUTHOR]

A 15-step total synthesis of (−)-lundurine A ( 1) from easily accessible ( S)-pyrrolidinone 18 is reported. A Simmons-Smith reaction allows the efficient, simultaneous assembly of the cyclopropyl C ring, the six-membered D ring, the seven-membered E ring, and the quaternary carbon stereocenters at C2 and C7. The absolute configuration of natural (−)-lundurine A was deduced to be 2 R,7 R,20 R based on the stepwise construction of the stereocenters during the total synthesis. [ABSTRACT FROM AUTHOR]

A step-economical and stereodivergent synthesis of privileged 2-arylcyclopropylamines (ACPAs) through a C(sp3)H borylation and Suzuki-Miyaura coupling sequence has been developed. The iridium-catalyzed CH borylation of N-cyclopropylpivalamide proceeds with cis selectivity. The subsequent B-cyclopropyl Suzuki-Miyaura coupling catalyzed by [PdCl2(dppf)]/Ag2O proceeds with retention of configuration at the carbon center bearing the Bpin group, while epimerization at the nitrogen-bound carbon atoms of both the starting materials and products is observed under the reaction conditions. This epimerization is, however, suppressed in the presence of O2. The present new ACPA synthesis results in not only a significant reduction in the steps required for making ACPA derivatives, but also the ability to access either isomer (cis or trans) by simply changing the atmosphere (N2 or O2) in the coupling stage. [ABSTRACT FROM AUTHOR]

In sharp contrast to the gold-catalyzed reactions of alkynes/allenes with nucleophiles, gold-catalyzed oxidative cross-couplings and especially CH/CH cross-coupling have been under represented. By taking advantage of the unique redox property and carbophilic π acidity of gold, this work realizes the first gold-catalyzed direct C(sp3)H alkynylation of 1,3-dicarbonyl compounds with terminal alkynes under mild reaction conditions, with subsequent cyclization and in situ oxidative alkynylation. A variety of terminal alkynes including aryl, heteroaryl, alkenyl, alkynyl, alkyl, and cyclopropyl alkynes all successfully participate in the domino reaction. The protocol offers a simple and region-defined approach to 3-alkynyl polysubstituted furans. [ABSTRACT FROM AUTHOR]

Hydride abstraction from the gold (disilyl)ethylacetylide complex [( P)Au{η1-CCSi(Me)2CH2CH2SiMe2H}] ( P=P( tBu)2 o-biphenyl) with triphenylcarbenium tetrakis(pentafluorophenyl)borate at −20 °C formed the cationic gold (β,β-disilyl)vinylidene complex [( P)AuCCS i(Me)2CH2CH2Si(Me)2]+B(C6F5)4− with ≥90 % selectivity. 29Si NMR analysis of this complex pointed to delocalization of positive charge onto both the β-silyl groups and the ( P)Au fragment. The C1 and C2 carbon atoms of the vinylidene complex underwent facile interconversion (Δ G≠=9.7 kcal mol−1), presumably via the gold π-disilacyclohexyne intermediate [( P)Au{η2- CCSi(Me)2CH2CH2Si (Me)2}]+B(C6F5)4−. [ABSTRACT FROM AUTHOR]