An enantioselective synthesis of the chiral bisnaphthopyrone natural product nigerone and its enantiomer, ent-nigerone, has been realized. The use of constrained 2-naphthol substrates was critical to producing highly functionalized chiral 1,1'-binaphthols via asymmetric oxidative biaryl coupling with 1,5-diaza-cis-decalin copper complexes. The final natural product was formed via a key eight-step isomerization process of the coupling product, bisisonigerone, and proceeded with retention of the biaryl configuration. The axial configurations of bisisonigerone and nigerone were definitively established by a combination of circular dichroism (CD) measurements and quantum chemical CD calculations.
[reaction: see text] An enantioselective synthesis of the chiral bisnaphthopyrone natural product nigerone is reported. The key step was an eight-step isomerization process to form the final natural product. The isomerization precursor was constructed via asymmetric oxidative biaryl coupling of an advanced intermediate with a 1,5-diaza-cis-decalin copper catalyst.
This paper describes the synthesis of hexa(ethylene glycol) and carboxymethylhexa(ethylene glycol)-terminated alkanedisulfides 4 and 7, respectively, in which the alkylene chains are twenty-methylenes-long. The key twenty-carbon synthon, 20-bromoicos-1-ene (1), was prepared by homologation of 8-bromooct-1-ene, which was achieved via Cu(II)-catalyzed coupling of the corresponding Grignard reagent with 1,12-dibromododecane. Compounds 4 and 7 are expected to yield self-assembled monolayers (SAMs) that are more stable and well-ordered than those formed by their traditional undecane homologues.Alkanethiols terminated by oligo(ethylene glycol) (OEG) groups have emerged as important reagents for forming biofunctionalized self-assembled monolayers (SAMs) on metal surfaces. 1 In a SAM, OEGs provide resistance to the nonspecific adsorption of proteins, while the alkylene chains tether the OEGs to the sulfur atoms and confer stability and order to the SAM through favorable interchain van der Waals contacts. The alkylene chains in these compounds are typically eleven-methylenes-long, owing to the commercial availability of the required eleven-carbon synthons, 11-haloundec-1-enes. 2 Despite the important role played by these groups, few studies have addressed the preparation of OEG-terminated thiols having alkylene chains that are longer than eleven methylenes. 3,4 Here, we describe the synthesis of hexa(ethylene glycol)-and (carboxymethyl)hexa(ethylene glycol)-terminated disulfides having alkylene chains that are twenty-methylenes-long ( Figure 1; compounds 4 and 7, respectively.) Figure 1 OEG-terminated icosanedisulfides prepared in this study.We chose to prepare 4 and 7 as symmetrical disulfides rather than as free thiols for two reasons. First, like free thiols, disulfides are known to be efficient and selective reagents for forming SAMs on metals such as gold. 4-6 Second, previous work by others has shown that oxidation of carboxyl-terminated alkanethiols to disulfides provides effective protection for the thiol group prior to transforming the carboxyl function. 5,6 An important result of these features is that carboxyl-terminated alkanedisulfides can be derivatized by amidation either before or after SAM formation. 6Our preparation of OEG-terminated icosanedisulfides (Scheme 1) is a modification of the method of Whitesides and co-workers for the synthesis of OEG-terminated undecanethiols, which employs the aforementioned commercially available 11-haloundec-1-enes. 2 Accordingly, we began by preparing the corresponding twenty-carbon synthon, 20-bromoicos-1-ene (1), by coupling octenyl magnesium bromide with 1,12-dibromododecane in THF using Li 2 CuCl 4 as catalyst. 7 Following multiple rounds of flash chromatography, we obtained 1 in modest yield (42%). Reaction of 1 with aqueous NaOH and ten equivalents of hexa(ethylene glycol) in refluxing THF and using tetrabutylammonium hydrogensulfate (TBAH) as phase-transfer catalyst afforded the monoether 2 in 72% yield. We note that this last reaction is an adaptation of the meth...
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