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An efficient protocol for the highly regio- and stereoselective synthesis of 4-(3′-hydroxy-2′-iodoalk-1′(Z)-enyl)furan-2(5H)-one derivatives via selective iodohydroxylation of non-heteroatom-substituted allenes, i.e., 4-allenyl-2(5H)furanones, has been developed. The regio- and stereoselectivity of this reaction may be controlled by the electronic and steric effects of the furanone ring.

An I^–-catalyzed methoxy carbon–oxygen bond cleavage in 5-methoxyoxazoles leading to the synthesis of azalactones, precursors of quaternary amino acids, has been developed. A series of 4-substituted azalactones were obtained through the variation of the alkyl iodides and differently substituted 5-methoxyoxazoles. Further study indicated that azalactone 3aa may be easily converted to benzoyl-protected quaternary amino acid 4aa. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2007)

In this paper, a bimolecular-cyclization reaction between two different bis(allene)s with at least one heteroatom as the tether under the catalysis of trans-[RhCl(CO)(PPh₃)₂] is described. This protocol provides an efficient entry to different heterocyclic 18,19-norsteroid-like scaffolds. The tricyclic product was formed highly selectively from the cyclization reaction of bis(2,3-butadienyl)sulfide with dimethyl 2-bis(2′,3′-butadienyl)malonate, which sheds light on the mechanism involving the metalla-[4.3.0]-bicyclic intermediate formed by the cyclometallation of the terminal and the internal C=C bonds of each of the two allene moieties in 2-bis(2′,3′-butadienyl)malonate.

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Von einer Chiralitätsachse zu einem Stereozentrum gelangt man hoch effizient in der regioselektiven Synthese von (1-Sulfonylalkyliden)thiiranen aus 1,2-Allenylsulfonen (siehe Schema). Ein cyclisches Intermediat aus der elektrophilen Addition von Brom an das Allen wurde isoliert und charakterisiert. Auf der Grundlage dieses Intermediats und der beobachteten Stereoselektivität wird ein Mechanismus vorgeschlagen.

Axial-to-central chirality transfer is highly efficient in a regioselective synthesis of (1-sulfonyl)alkylidenethiiranes from 1,2-allenyl sulfones (see scheme). A cyclic intermediate formed upon the electrophilic addition of bromine to the allene was isolated and characterized. A mechanism is proposed on the basis of this intermediate and the observed stereoselectivity.

Pyrazolidines containing two chiral centers, an interesting class of heterocyclic compounds possessing a range of biological activities, have been prepared highly diastereoselectively (up to 95:5) through asymmetric Pd(OAc)₂-catalyzed cyclizations between the easy available optically active allenylic hydrazines and organic halides in THF in the presence of (R,R)-Bn-Box (L2) as the ligand. It was observed 1) that in most cases (3R,5S)-pyrazolidines were obtained in good yields with very high enantiopurities (>99%) and high diastereoselectivities (up to 95:5) in the presence of (R,R)-Bn-Box (L2), 2) that aryl halides containing electron-donating or -withdrawing groups, heteroaryl, and 1-alkenyl iodides are all suitable substrates for this diastereoselective cyclization, 3) that the absolute configurations of the newly formed chiral centers in the pyrazolidines depend on the structure of substrate 1, and 4) that the enantio- and diastereopurities of the trans-pyrazolidines are co-controlled by the chiralities of the chiral catalysts and the substrates. A model for prediction of the enantiopurities of the products and the diastereoselectivities of the reactions based on an HPLC study of the starting hydrazines and the products was established.

The palladium-catalyzed coupling–cyclization of β-amino allenes with organic halides ranging from aryl halide to 1-alkenyl halide was studied. 2,3-Dihydro-1H-pyrroles were obtained by reaction of 3-substituted-5-unsubstituted-3,4-allenyl amides under conditions A, while the reaction of 5-substituted-3,4-allenyl amides afforded 1,2,5,6-tetrahydropyridines and/or azetidines with high de under conditions B or C. The skeleton and relative configuration of the six-membered products were established by the X-ray diffraction studies of 10 ka. Allenyl amide 4 q reacted with 1,4-diiodobenzene 6 r to afford double cyclization product 15. The structure of its major stereoisomer was also determined by the X-ray diffraction study.

A highly regio- and stereoselective syn-carbometalation of terminal secondary or tertiary propargylic alcohols with primary alkyl Grignard reagents in toluene or phenylmagnesium bromide in Et₂O was developed, in which the alkyl or phenyl group from the Grignard reagents is introduced into the terminal position of the alcohols. The organometallic intermediate formed may be used directly for the coupling reaction with organic halides. Upon treatment with I₂ after the carbometalation, iodides may be obtained, which may undergo Sonogashira coupling reaction and highly stereoselective Novozym-435-catalyzed kinetic resolution to afford the optically active products.

The activation of CCl bond of (Z)-α-chloroalkylidene-β-lactones and (E)-α-chloroalkylidene-β-lactams via the Suzuki cross-coupling reaction is reported in this paper. Alkyl, heteroaromatic, substituted phenyl- and alkenylboronic acids can be coupled with a wide variety of α-chloroalkylidene-β-lactones and β-lactams in excellent yields within a short period of time. The cross-coupling reaction of optically active substrates leads to the optically active compounds without racemization of the corresponding chiral center.

Ansonsten schwer fassbare trisubstituierte (Z)-1-Alkenylphosphonate erhält man durch partielle Hydrierung von Allenylphosphonaten in Gegenwart des Pd-Komplexes 1. Viele dieser Reaktionen zeichnen sich durch hohe Ausbeuten, Chemo-, Regio- und Stereoselektivitäten aus. Ähnlich funktionalisierte Allene sind gleichfalls geeignet und liefern die entsprechenden Z-konfigurierten Alkene (siehe Schema). R¹=H, Alkyl, Aryl, Benzyl; R²,R³=H, Alkyl; FG=P(O)(OR)₂, P(O)Ph₂, SO₂Ph, COOEt.

In Bewegung: Bei einer Pd(OAc)₂-katalysierten Kupplung/Cyclisierung von 2,3-Allencarbonsäuren mit Methylpropiolat in Gegenwart von [Sc(OTf)₃]/BF₃⋅Et₂O (OTf=Triflat) tritt eine „π-Bindungswanderung“ der 1:2-Addukte auf, die möglicherweise über doppelte 1,7-H-Verschiebungen verläuft.

Auf geht's, Allene: Durch gezielte Kopf-Kopf- oder Schwanz-Schwanz-[2+2]-Cycloaddition wurden 1,5-Bisallenylverbindungen in [3.2.0]- bzw. [5.2.0]bicyclische Verbindungen überführt (siehe Schema). Die bicyclischen Produkte enthalten Doppelbindungen, die sich für weitere Umsetzungen eignen.

Der Schlüsselschritt der goldkatalysierten Cycloisomerisierung von Eninen ist der nucleophile Angriff auf die Au-koordinierte C-C-Dreifachbindung unter Bildung eines Vinylgold-Intermediats (siehe Beispiel). Der homogenkatalysierte Prozess läuft unter milden Bedingungen ab und liefert hoch effizient komplexe oder anderweitig nicht zugängliche Produkte.

Come on allenes: [2+2] Cycloadditions of 1,5-bisallenyl compounds were realized in controllable head-to-head and tail-to-tail manners, resulting in the formation of [3.2.0] and [5.2.0] bicyclic compounds, respectively (see scheme). The bicyclic compounds include double bonds suitable for further elaboration and thus these reactions may be powerful tools in organic synthesis.

On the move: A Pd(OAc)₂-catalyzed coupling/cyclization reaction of 2,3-allenoic acids with methyl propiolate in the presence of [Sc(OTf)₃]/BF₃⋅Et₂O (OTf=triflate) leads to a “π-bond migration” in the 1:2 adducts, which may proceed through double 1,7-hydrogen migrations.

Often elusive, trisubstituted (Z)-1-alkenyl phosphonates can be prepared by the semihydrogenation of allenyl phosphonates in the presence of Pd complex 1. This reaction, which occurs in high yield with high chemo-, regio-, and stereoselectivity, can be extended to related functionalized allenes and the corresponding Z alkene products (see scheme). R¹=H, alkyl, aryl, benzyl; R²,R³=H, alkyl; FG=P(O)(OR)₂, P(O)Ph₂, SO₂Ph, COOEt.

The clean isomerization of 1,2-allenyl sulfoxides in the presence of NaSO₂Ph afforded 2-alkynylic phenyl sulfoxides in good yields and selectivities. Although strong base-catalyzed isomerization of allenes to alkynes is known, the mechanism for the current reaction is interesting for the obvious reason that NaSO₂Ph is a weak base.

Three sets of convenient catalytic systems have been developed for the oxidative dimeric cyclization coupling of differently substituted 2,3-allenoic acids catalyzed by Pd^II, affording bibutenolides that are not otherwise readily available. The advantages and disadvantages of these systems are discussed. Although the diastereoselectivity for the bicyclization of racemic 2,3-allenoic acids is low, excellent diastereoselectivity was realized in the bicyclization reaction of optically active 2,3-allenoic acids, leading to the optically active bibutenolides in high yields and ee. Based on a mechanistic study, it is believed that the reaction may proceed by means of a double oxypalladation and reductive elimination to yield butenolide 3 and Pd⁰ species, which may be reoxidized to the catalytically active Pd^II species in the presence of alkyl iodide/air, metallic iodide/air, or benzoquinone.

Three key intermediates in the palladium-catalyzed reaction of allenes with organoboronic acids in the presence of AcOH have been characterized by high resolution ESI-FT mass spectrometry (see picture). Their observation allows a better understanding of the reaction mechanism.

The beauty and power of transition-metal-catalyzed reactions has been demonstrated by the one-step synthesis of steroid scaffolds from readily available allenes. The best results (57–73 % yield) were obtained using trans-[RhCl(CO)(PPh₃)₂] as the catalyst in toluene (see scheme; E=CN, CO₂Me, SO₂Ph, Ts=toluene-4-sulfonyl).

Drei Schlüsselintermediate der palladiumkatalysierten Reaktion von Allenen mit Organoboronsäuren in Gegenwart von AcOH wurden durch hochauflösende ESI-FT-Massenspektrometrie charakterisiert (siehe Bild). Der Nachweis dieser Spezies wirft Licht auf den Reaktionsmechanismus.

Mechanismen, die auf der 1,4-Wanderung von Metallzentren beruhen, sind zur Erklärung einiger interessanter Übergangsmetall-katalysierter Umsetzungen herangezogen worden. Trotz der nur wenigen belastbaren Belege lässt sich postulieren, dass die 1,4-Metallwanderung über die reduktive Eliminierung von dreifach gebundenen Intermediaten bei Rhodium-katalysierten Umsetzungen sowie von vierfach gebundenen Intermediaten bei Palladium-katalysierten Prozessen abläuft. Diese hochvalenten metallorganischen Spezies sollten sich durch oxidative Addition an die C-H- und C-X-Bindungen bilden. Dieser Kurzaufsatz fasst die Ergebnisse auf diesem Gebiet zusammen.

The E-iodohydroxylation of 1, 2-allenylic sulfoxides with I₂ in the presence of EtOH afforded 3-phenylsulfinyl-2–10do-2(E)-alkenols in good yields and regio/stereo-selectivities under very mild conditions.

Optically active I-aryl-2.3-allenols were obtained via CCL-mediated kinetic resolution of the racemic allenols. The substitution pattern of the aromatic rhg. regarding to both the type of the substituent and its position on the aromatic ring, was found to be critical for the kinetic resolution of l-aryl-2, 3-allenols.

The double ring-closing metathesis reaction of nitrogen-containing tetraenes was studied. The selectivity of the fused/dumbbell-type products can be controlled by the electronic/steric effects of the substituents attached to the CC bonds and the s-cis/s-trans conformational ratios of the substrates. This methodology has also been successfully applied to the enantioselective synthesis of four stereoisomers of lupinine and their derivatives.

The oxidative cyclization/dimerization reaction between two classes of allenes with different functionalities was reported to provide an efficient route to polysubstituted 4-(3′-furanyl)-2(5H)-furanones, which are not readily available from the known methods. The highly optically active butenolides could be easily formed from the optically active 2,3-allenoic acids, which was obtained conveniently through chiral resolution with optically active amines, that is, cinchonidine or α-methyl benzylamine. A mechanistic study showed that the reaction proceeded via a matched double oxypalladation–reductive elimination process. The Pd^II species may be regenerated via the subsequent cyclometallation of two equivalents of 1,2-allenyl ketones with Pd⁰ and protonlysis of Pd enolates formed with the in situ generated HCl.

The lithiation reagent and temperature may be the key factors controlling the 1,3-lithium shift of propargylic/allenylic lithium (see scheme). Under the right conditions, 1,1-diarylallenes and 1,3-diarylallenes can be easily and highly selectively synthesized by the lithiation of 1-aryl-1-alkynes and the subsequent transmetalation (1), and Pd-catalyzed coupling with aryl halides (2).

The Pd⁰-catalyzed regio- and stereoselective addition of organoboronic acids to allenes leads to stereodefined tri- or tetrasubstituted alkenes. Furthermore, this method shows high substitutent-loading capability and tolerance of various substitutents. A hydropalladation–Suzuki coupling mechanism, which may account for the regio- and stereoselectivity, is proposed.