The tandem asymmetric conjugate addition of alkyl or aryl groups to enones and subsequent silyl trapping has already been achieved and yields valuable silyl enol ethers. Herein, the first method for the respective addition of alkenyl groups is reported, which is based on a rhodium(I)‐catalyzed addition of readily available alkenylzirconocenes. As prerequisite for silyl trapping, the initially formed enolates have to be transmetalated from zirconium to lithium by treatment with methyllithium prior to addition of the silyl chloride. Starting from 5‐ to 7‐membered cycloalkenones, the respective silyl enol ethers were obtained in excellent yields and ≥93% ee; an acyclic substrate furnished a moderate enantioselectivity. Besides trimethylsilyl chloride, the silylation was also performed with tert‐butyldimethylsilyl chloride, and the synthetic scope was evaluated by employing five different alkenyl groups. Moreover, the mechanism of this sequence was elucidated by 1H NMR studies, and the efficiency of catalyst control was exemplified by synthesis of a cis‐3,5‐disubstituted cyclohexanone which, due to strong substrate control, cannot be obtained by copper‐catalyzed conjugate addition.magnified image

Among carbon-carbon bond-forming processes the 1,2-addition of metal organyl compounds to carbonyl moieties is one of the major reactions in organic synthesis. In the last decade methods based on transition-metal catalysis have been developed that allow stereoselective reactions with a broad spectrum of aldehydes.[1] However, ketones and especially enones still are problematic substrates for which only few catalyst systems are suitable.[2] In contrast, asymmetric 1,4-additions of a variety of organometallic compounds to enones by copper, palladium, and rhodium catalysis are well-established.[3] During our studies towards the total synthesis of the natural product spirodionic acid [4] we envisaged such Rhcatalyzed enantioselective Michael additions to cyclic enones, yet employing aluminum organyl compounds, which-to the best of our knowledge-have hitherto not been used in combination with Rh catalysts. [5] Cyclohex-2-enone (2) was treated with [{Rh(cod)Cl} 2 ] (cod = cyclooctadiene) and an equimolar amount of AlMe 3 to give the desired 3-methylcyclohexanone (1, Scheme 1). To perform the transformation enantioselectively, in situ prepared [{Rh[(S)-binap]Cl} 2 ] was used next; yet the use of this complex led to a dramatic change of the reaction course. Highly selective 1,2-addition was observed and 1-methylcyclohex-2-enol (3) was formed with 96 % ee. Since this compound is a known aggregation pheromone of the Douglas-fir beetle, previously only available in multistep syntheses, [6] the R configuration could be assigned to the product 3 based on the reported optical rotation.The formation of 3 from 2 appears to be the first example of an enantioselective Rh-catalyzed 1,2-addition to an enone; thus, the reaction conditions were optimized. [7,8] On lowering the temperature to 0 8C or À20 8C the enantioselectivity was only slightly increased to 98 % ee, while the reaction was significantly retarded (Table 1, entries 1-3). Variation of the precatalyst led to similar results when starting from complexes with noncoordinating or bidentate counterions (Table 1, entries 4 and 5), yet significant improvements were achieved when using [{Rh(cod)OMe} 2 ], thus increasing the yield to 97 % with 99 % ee (entry 6). In a second set of experiments the catalyst loading was reduced, which still gave good results with 1 mol %, but almost no conversion with 0.1 mol % (Table 1, entries 7-9).Furthermore, the influence of the solvent was examined, revealing that THF is the best choice. With other ethers the yield decreased in the order 1,2-dimethoxyethane > dioxane > Et 2 O; hydrocarbons such as toluene proved unsuitable owing to significant background reactivity.[9] To gain insight into the sudden change of the reaction course, various monoand bidentate phosphine ligands were tested (PPh 3 , PnBu 3 , dppe, dppb, diop), [10] yet none of them led to the formation of the 1,4-adduct 1 or the 1,2-adduct 3 in more than 10 % yield. Furthermore, no conversion occurred in the presence of binap when omitting the Rh precatalyst, thus proving catalysis...

Professor Armin de Meijere gewidmetDie 1,2-Addition von Organometallverbindungen an Carbonylgruppen zählt zu den wichtigsten Methoden der C-CBindungsbildung in der organischen Synthese. In den vergangenen Jahren wurden übergangsmetallkatalysierte Verfahren entwickelt, nach denen sich unterschiedlichste Aldehyde stereoselektiv umsetzen lassen.[1] Dagegen gestaltet sich die entsprechende Transformation von Ketonen und insbesondere konjugierten Enonen immer noch schwierig, und es existieren hierfür nur wenige geeignete Katalysatorsysteme. [2] Asymmetrische 1,4-Additionen von Organometallverbindungen an a,b-ungesättigte Ketone unter Cu-, Pd-und RhKatalyse wurden dagegen ausführlich beschrieben.[3] Bei unseren Arbeiten zur Totalsynthese des Naturstoffs Spirodionsäure [4] untersuchten wir solche Rh-katalysierten enantioselektiven Michael-Additionen an cyclische Enone, wobei wir von Organoaluminiumverbindungen ausgingen, die unseres Wissens bislang noch nicht in Verbindung mit Rh-Katalysatorsystemen verwendet wurden. Katalysator eingesetzt, wobei die Reaktion nun einen anderen Verlauf nahm. Statt der beabsichtigten 1,4-Addition wurde eine hochselektive 1,2-Addition beobachtet, die 1-Methylcyclohex-2-enol (3) mit einem Enantiomerenüber-schuss (ee) von 96 % lieferte. Der Allylalkohol 3 ist ein Aggregationspheromon des Douglasien-Borkenkäfers, dessen mehrstufige Synthese bereits beschrieben wurde, [6] sodass wir dem Produkt der Umsetzung anhand des optischen Drehwerts die R-Konfiguration zuweisen konnten.Da die Reaktion von 2 zu 3 offenbar die erste enantioselektive Rh-katalysierte 1,2-Addition an ein Enon ist, wurden zunächst die Reaktionsparameter sorgfältig optimiert. [7,8] Bei Reaktionstemperaturen von 0 8C oder À20 8C konnte eine geringfügig höhere Enantioselektivität festgestellt werden (98 % ee), allerdings bei deutlich geringerer Reaktionsgeschwindigkeit (Tabelle 1, Einträge 1-3). Mit anderen Katalysatorvorstufen ergaben sich keine nennenswerten Unterschiede, sofern Komplexe mit nichtkoordinierenden oder zweizähnigen Gegenionen eingesetzt wurden (Tabelle 1, Einträge 4 und 5). Mit [{Rh(cod)OMe} 2 ] erhöhte sich hingegen die Ausbeute auf 97 % bei 99 % ee (Eintrag 6). Auch mit nur 1 Mol-% des in situ gebildeten Komplexes wurden immer noch gute Ergebnisse erzielt, mit 0

The development of an improved protocol for the enantioselective Rh(I) /binap-catalysed 1,2-addition of AlMe3 to cyclic enones is reported. (31)P NMR analysis of the reaction revealed that the catalyst in its resting state is a chloride-bridged dimer. This insight led to the use of AgBF4 as an additive for in situ activation of the dimeric precatalyst. Thus, the catalyst loading can now be reduced to only 1 mol% with respect to rhodium. Various 5-7-membered cyclic enones can be transformed into tertiary allylic alcohols with excellent levels of enantioselectivity and high yields. The obtained products are versatile synthetic building blocks, shown by a highly enantioselective formal total synthesis of the pheromone (-)-frontalin as well as formation of a bicyclic lactone that has the core structure of the natural flavour component "wine lactone".

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