The direct catalytic asymmetric aldol reaction using aldehydes and unmodified ketones is described for the first time herein. This reaction was first found to be promoted by 20 mol % of anhydrous (R)-LLB (L = lanthanum, L = lithium, B = (R)-binaphthol moiety) at −20 °C, giving a variety of aldol products in ee's ranging from 44 to 94%. This asymmetric reaction has been greatly improved by developing a new heteropolymetallic asymmetric catalyst [(R)-LLB, KOH, and H2O]. Using 3−8 mol % of this catalyst, a variety of direct catalytic asymmetric aldol reactions were again found to proceed smoothly, affording aldol products in ee's ranging from 30 to 93% and in good to excellent yields. Interestingly, the use of this new heteropolymetallic asymmetric catalyst has realized a diastereoselective and enantioselective aldol reaction using cyclopentanone for the first time. It is also noteworthy that a variety of aldehydes, including hexanal, can be utilized for the current direct catalytic asymmetric aldol reaction. Chiral aldehydes containing α-hydrogen including (S)-hydrocinnamaldehyde-α-d have been found to produce the corresponding aldol products with negligible racemization (0−4%) at the α-position. One of the aldol products has been successfully converted to the key synthetic intermediates of epothilone A and bryostatin 7. The possible structure of the heteropolymetallic catalyst is also discussed. Finally, mechanistic studies have revealed a characteristic reaction pathway, namely that the reaction is kinetically controlled and the rate-determining step is the deprotonation of the ketone. This is consistent with the fact that the reaction rate is independent of the concentration of the aldehyde.

The aldol reaction is one of the most powerful ofcarbon-carbon bond-forming reactions, and the development of a range of catalytic asymmetric aldol-type reactions has thus proven to be a valuable contribution to asymmetric synthesis. ['] In all of these asymmetric aldol-type reactions, however, pre-conversion of the ketone moiety to a more reactive species such as an enol silyl ether, enol methyl ether, or ketene silyl acetal is an unavoidable necessity. Development of a direct catalytic asymmetric aldol reaction, starting from aldehydes and unmodzfed ketones is thus a worthwhile endeavor.I2] Such reactions are known in enzyme chemistry:[31 the fructose-I ,6-bisphosphate and dihydroxyacetone phosphate (DHAP) aldolases are characteristic examples. The mechanism of these is thought to involve cocatalysis by a Zn2' ion and a basic functional group in the enzyme's active site; the latter abstracts a proton in proximity to a carbony1 compound while the former functions as a Lewis acid to activate the second carbonyl component. These aldolases can thus be thought of as multifunctional catalysts displaying both Lewis acidity and Br~nsted basicity, so making possible efficient catalytic asymmetric aldol reactions under typically mild in vivo conditions. An analogous cooperative mode of action can be seen in reactions mediated by any of several heterobimetallic asymmetric catalysts having both Lewis acidity and Brsnsted basicity, which have been developed by our research gr0~1p.I~.We speculated that it might be possible to develop a direct catalytic asymmetric aldol reaction of aldehydes with unmodified ketones by employing catalysts like I (Scheme 1). A Brsnsted base unit (OM) of catalyst I could deprotonate an or-proton of a ketone to generate the metal enolate 11, while at the same time a Lewis acid unit (LA) could activate an aldehyde to give 111. These reaction partners might react in the chelationcontrolled, asymmetric environment to afford a P-keto metal alkoxide (IV). Proton exchange between the metal alkoxide moiety and a hydroxy proton of the aryl unit or an a-proton of e-mail: rnshibasairr mol.fu-tokyo.ac.jp a ketone could then generate an optically active aldol adduct with regeneration of the catalyst I. We now wish to report the first example of such a reaction,l6] in which we have obtained optically active aldol adducts in up to 94% ee.We were initially concerned that our heterobimetallic asymmetric catalysts would be ineffective at promoting aldol reactions as a result of their rather low Brernsted basicity and were thus pleased to find that aldol reactions of the desired type proceeded quite smoothly with LaLi,tris(binaphthoxide) (LLB)[4d1 as catalyst (Figure 1). As shown in Table 1, when the [a] (R)-LLB and addition of 1 equiv of H,O to LLB, see ref.[lo].[b] The reaction was carried out at -30 "C direct catalytic asymmetric aldol reaction of pivalaldehyde (la) with 5.0 equivalents of acetophenone (Za) was carried out in the presence of 20 mol% of (R)-LLB and 1.0 equivalent of H,O (relative to LLB) in TH...

Self-assembly of copper sulfate and a poly(imidazole-acrylamide) amphiphile provided a highly active, reusable, globular, solid-phase catalyst for click chemistry. The self-assembled polymeric Cu catalyst was readily prepared from poly(N-isopropylacrylamide-co-N-vinylimidazole) and CuSO(4) via coordinative convolution. The surface of the catalyst was covered with globular particles tens of nanometers in diameter, and those sheetlike composites were layered to build an aggregated structure. Moreover, the imidazole units in the polymeric ligand coordinate to CuSO(4) to give a self-assembled, layered, polymeric copper complex. The insoluble amphiphilic polymeric imidazole Cu catalyst with even 4.5-45 mol ppm drove the Huisgen 1,3-dipolar cycloaddition of a variety of alkynes and organic azides, including the three-component cyclization of a variety of alkynes, organic halides, and sodium azide. The catalytic turnover number and frequency were up to 209000 and 6740 h(-1), respectively. The catalyst was readily reused without loss of catalytic activity to give the corresponding triazoles quantitatively.

Germination stimulants for root holoparasitic weeds broomrapes ( Orobanche and Phelipanche spp.) produced by tobacco ( Nicotiana tabacum L.) were purified and characterized. The root exudates of tobacco contained at least five different stimulants, and LC-MS/MS analyses revealed that four of them were strigolactones; a tetradehydrostrigol isomer, a didehydrostrigol isomer, and two strigol isomers. The two isomers of strigol were identified as (+)-orobanchol and its 2'-epimer by comparison of NMR and GC- and LC-MS data with those of synthetic standards. The structure of the tetradehydrostrigol isomer, the major stimulant of the bright yellow tobacco cultivars, was determined as 4-alpha-hydroxy-5,8-dimethyl-GR24 [( E)-4-alpha-hydroxy-5,8-dimethyl-3-(4-methyl-5-oxo-2,5-dihydrofuran-2-yloxy)methylene)-3a,4-dihydro-3 H-indeno[1,2- b]furan-2(8b H)-one] and named solanacol. 2'-Epi-orobanchol and solanacol are the first natural strigolactones having a 2'-epi stereochemistry and a benzene ring, respectively.