Ethers Kagan

In 2000, Kagan and Holmes reported that the mono-lithium salt 10 of (R)- or (S)-BINOL catalyzes the addition of TMS-CN to aldehydes (Scheme 6.8) [52]. The mechanism of this reaction is believed to involve addition of the BI NO Late anion to TMS-CN to yield an activated hypervalent silicon intermediate. With aromatic aldehydes the corresponding cyanohydrin-TMS ethers were obtained with up to 59% ee at a loading of only 1 mol% of the remarkably simple and readily available catalyst. Among the aliphatic aldehydes tested cyclohexane carbaldehyde gave the best ee (30%). In a subsequent publication the same authors reported that the salen mono-lithium salt 11 catalyzes the same transformation with even higher enantioselectivity (up to 97% Scheme 6.8) [53], The only disadvantage of this remarkably simple and efficient system for asymmetric hydrocyanation of aromatic aldehydes seems to be the very pronounced (and hardly predictable) dependence of enantioselectivity on substitution pattern. Furthermore, aliphatic aldehydes seem not to be favorable substrates. 

Kagan and Schiffers carefully studied the effect of the lithium salts of BINOL (17) and related axially chiral binaphthols on the reduction of a variety of ketones with trialkoxysilanes [24]. They found that diethyl ether, with TMEDA as an additive, was the best solvent for asymmetric reduction of ketones. In the presence of 5 mol% of the monolithium salt of BINOL (17), acetophenone (1) could be reduced with trimethoxysilane in 80% yield and with 61% ee. Enantiomeric excesses > 90% were achieved under the same conditions with 2, 4, 6 -trimethyl-acetophenone (18) or a-tetralone (19) as substrates. Aliphatic ketones such as... 

Kagan and co workers studied the reaction between cyclopentadiene and 310 in the presence of aluminum alcoholates of chiral diols and their chiral mono ethers. Among the various diols studied, only 1,1-diphenyl-1,2-propanediol (325) gave satisfactory results. Optimization by variation of the dienophile/catalyst ratio, aging of the catalyst and variation of the temperature ultimately resulted in a maximum of 86% ee at — 100°C. 

Kagan was the first to study reactions in which enantioselectivity at a prochiral nucleophile was examined. In the reaction of 2-acetyltetralone with allylic ethers in the presence of a chiral DIOP-Pd catalyst, Eq. (10), the allylated products were obtained with ee s of only 10% [34]. 

Acid treatment of arylethanals may lead to 2-phenylnaphthalenes or l,2,9,10-tetrahydro-l,9-epoxydibenzo[a,e]cyclooctenes (Kagan s ether). 2-Phenylnaphthalenes were obtained by a C-condensation of the enolated form on the keto form. The resulting aldol condensation product underwent an intramolecular reaction to give, after rearomatisation, the 2-phenylnaphthalenes, Fig. (1). 

Fig. (2). Mechanim of formation of Kagan s ether (example is given with boron tribromide as Lewis acid)...

More curiously, N-tosylated phenylalanine derivatives [10] and phenyllactic acid [11] can also be converted into 2-phenylnaphthalene in moderate yields whereas 3,4-dimethoxyphenyllactic acid treated with boron tribromide gives Kagan s ether in almost the same yield as 3,4-dimethoxyphenylethanal does [11]. In these cases, the decomposition of aryllactic acid or alanine derivatives may give arylethanal with the formation of water and carbon monoxide, Fig. (4). 

Kagan s ether structurally related compounds have not been found in Nature but their nitrogen analogues belong to the pavine alkaloid family. Pavinan and isopavinan alkaloids can be formally viewed as oxidatively cyclised 1-benzyl-1,2,3,4-tetrahydroisoquinolines and are most frequently obtained by acid-catalysed cyclisation of appropriately oxidised congeners of these isoquinolines [13]. Numerous attempts have been made to convert Kagan s ethers into pavine, but all were unsuccessful [4]. 

Cram has prepared a host system consisting of four linked dibenzofurans (430). One variation was found to form a complex with guanine in methanol <92JA10775>. Bisdibenzofuran (431), a derivative of Kagan s ether, is a molecular tweezer that binds to trinitrobenzene <90JA5655>. 

The first use of rare earth metals in the aldol reaction began in the case of cerium enolate (198). Subsequently, Kagan and Kobayashi groups reported systematically the use of rare earth metalscatalyzed for the Mukaiyama aldol-type reaction of silyl enol ethers with aqueous formaldehyde solution (199,200). The efficiency of rare earth metals in a Mukaiyama aldol reaction of 1-trimethylsiloxycyclohexene with benzaldehyde was examined in aqueous THF (Scheme 52). Of the rare earth metal trifiates screened, catalytic efficiency was increased in the order of Yb (91%) > Gd (89%) > Lu (88%) > Nd (83%) > Dy (73%) > Er (52%) > Ho(47%) > Sm (46%) > Eu (34%) > Tm (20%) > La (8%) > Y (trace) (201,202). For different aldol or aldol-type reactions, every rare earth metal occupied its special position in the aldol reaction with distinctive catalytic activity. There were several reviews concerning the rare earth metals catalyzed aldol reactions (203,204). New progress in this context will be discussed herein according to rare earth metals catalysis especially for the past 10 years. 

Functionalized analogues of Kagan s ether (159) have been prepared via a one-pot cascade dimerization of orf/to-alkynylbenzaldehydes in acetic acid, with aqueous HBF4 catalysis. ... 

Kagan reported in 1983 the synthesis of the whole series of H—T —H via organoboranes [26d]. The oligomers can be prepared separately in acceptable yields with organoborane reagents. To a solution of Li—T —H 9, 15, 16, 28, the 9-methoxy derivative of 9-borabicyclo[3.3.1]nonane is added and a corresponding boronated thiophene 29-32 is formed [Eq. (12)]. After neutralization with boron trifluoride etherate, a second Li—T -H, which may differ from the previous one, is added to boranes 33-36 and the resulting complex 37-41 is oxidized with iodine in order to... 

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