Copper-Catalyzed Oxidative C-H Bond Functionalization of N-Allylbenzamide for Regioselective C-N and C-O Bond Formation.

Copper-catalyzed oxidative couplings of N-allylbenzamides for C-N and C-O bond formations have been developed through C-H bond functionalization. To demonstrate the utility of this approach, it was applied to the synthesis of ß-aminoimides and imides. To the best of our knowledge, these are the first examples in which different classes of N-containing compounds have been directly prepared from the readily available N-allylbenzamides using an inexpensive catalyst/oxidant/base (CuSO4 /TBHP/Cs2 CO3 ) system.

"Diversity oriented synthesis" of functionalized chiral tetrahydropyridines: potential GABA receptor agonists and azasugars from natural amino acids via a sequential Baylis-Hillman reaction and RCM protocol.

The preparation of chiral tetrahydropyridine-4-carboxylates as isoguvacine analogues and azasugars with a tertiary stereocenter from L-amino acids via diastereoselective a Baylis-Hillman reaction of N-allyl-Boc alpha-aminal, followed by ring-closing metathesis and dihydroxylation sequences, is reported.

Diversely substituted sugar-linked alpha,beta-unsaturated gamma-lactones from sugar-derived Baylis-Hillman adducts via a RCM.

A versatile protocol for the production of sugar-linked alpha,beta-unsaturated gamma-lactones with stereochemical and functional group diversity is described starting from sugar-derived Baylis-Hillman adducts via ring-closing metathesis.

Differentiation of Boc- alpha,beta- and beta,alpha-peptides and a pair of diastereomeric beta,alpha-dipeptides by positive and negative ion electrospray tandem mass spectrometry (ESI-MS/MS).

Positive and negative ion electrospray ionization (ESI) tandem mass spectral study of a new series of hybrid peptides, viz, BocN-alpha,beta-peptides and BocN-beta,alpha-peptides, synthesized from C-linked carbo-beta3-amino acids [Caa (S)] and L-Ala has been carried out. The alpha,beta-peptides have been differentiated from beta,alpha-peptides by the collision-induced dissociation (CID) of [M + H]+ and [M - H]- ions in positive and negative ion ESI-MS respectively. The fragment ion [M + H - C(CH3)3 + H]+ formed from [M + H]+ ions by the loss of 2-methyl-prop-2-ene in alpha,beta-peptides with L-Ala at the N-terminus is insignificant or totally absent for beta,alpha-peptides which have the Caa (S) at N-terminus. The fragment ion [M - H-C(CH3)3OH - HNCO]- formed from [M - H]- of beta,alpha-peptide acids is totally absent for alpha,beta-peptide acids. This has been attributed to the absence of the beta-methylene group in alpha,beta-peptides, and the participation of the beta-methylene group in the loss of HNCO in beta,alpha-peptide acids is confirmed by the deuteration experiments. The CID of [M + H-Boc + H]+ ions of these peptides also produce characteristic fragmentation. In the CID spectra of alpha,beta-peptides, the b(n)+ ions and the resulting y(n)+ ions occur at a mass difference of 243 and 71 Da corresponding to the successive losses of Caa and L-Ala, whereas a mass difference of 71 and 243 Da is observed for beta,alpha-peptides. In contrast to the CID of protonated peptides, the CID of [M - H]- ions of the alpha,beta- and beta,alpha-peptide acids do not give b(n)- ions and show abundant z(n) (-) ions. Further, a pair of diastereomeric dipeptide esters and acids have been distinguished by the CID of [M + H]+ ions. The loss of 2-methyl-prop-2-ene is more pronounced for Boc-NH-Caa(R)-D-Ala-OCH3 (21) and Boc-NH-Caa(R)-D-Ala-OH (23) with Caa (R) at the N-terminus, whereas it is totally absent for Boc-NH-Caa (S)-D-Ala-OCH3 (22) and Boc-NH-Caa(S)-D-Ala-OH (24) peptides, which have Caa (S) at the N-terminus. Thus, on the basis of our previous and present studies, we propose that the CID of [M + H]+ ions provides a simple and useful method for distinguishing the configuration of Caa (S or R) at the N-terminus of BocN-carbo beta,alpha- and beta,beta-dipeptides.

'Double asymmetric induction' as a novel tool for high stereocontrol in Baylis-Hillman reaction.

The strategy of double asymmetric induction was utilized in Baylis-Hillman reaction for the first time by the coupling of chiral aldehydes with chiral acrylate (1,2:5,6-di-O-isopropylidene-alpha-D-glucofuranose-3-acrylate) to obtain corresponding adducts with high syn diastereoselectivities (de >90%) in moderate to good yields.

Mass spectral study of alkali-cationized Boc-carbo-beta3-peptides by electrospray tandem mass spectrometry.

Electrospray tandem mass spectrometry was used to study the dissociation reactions of [M+Cat]+ (Cat = Na+ and Li+) of Boc-carbo-beta3-peptides. The collision-induced dissociation (CID) spectra of [M+Cat-Boc]+ of these peptides are found to be significantly different from those of [M+H-Boc]+ ions. The spectra are more informative and display both C- and N-terminus metallated ions in addition to characteristic fragment ions of the carbohydrate moiety. Based on the fragmentations observed in the CID spectra of the [M+Cat-Boc]+ ions, it is suggested that the dissociation involves complexes in which the metal ion is coordinated in a multidentate arrangement involving the carbonyl oxygen atoms. The CID spectra of [M+Cat-Boc]+ ions of the peptide acids show an abundant N-terminal rearrangement ion [b(n)+17+Cat]+ which is absent for esters. Further, two pairs of positionally isomeric Boc-carbo-beta3-peptide acids, Boc-NH-Caa(S)-beta-hGly-OH (11) and Boc-NH-beta-hGly-Caa(S)-OH (12), and [Boc-NH-Caa(S)-beta-hGly-Caa(S)-beta-hGly-OH] (13) and [Boc-NH-beta-hGly-Caa(S)-beta-hGly-Caa(S)-OH] (14), were differentiated by the CID of [M+Cat-Boc]+ ions. The CID spectra of compounds 11 and 13 are significantly different from those of 12 and 14, respectively. The abundance of [b(n)+17+Cat]+ ions is higher for peptide acids 12 and 14 with a sugar group at the C-terminus when compared to 11 and 13 which contain a sugar moiety at the N-terminus. The observed differences between the CID spectra of these isomeric peptides are attributed to the difference in the preferential site of metal ion binding and also on the structure of the cyclic intermediate involved in the formation of the rearrangement ion.

First diastereoselective intramolecular Baylis-Hillman reaction: an easy access to chiral alpha-methylene-beta-hydroxylactones.

The first diastereoselective intramolecular Baylis-Hillman reaction of chiral substrates is reported wherein both aldehyde and activated olefin coexist as substituents to afford alpha-methylene-beta-hydroxylactones in good yields exclusively as single isomers under the standard base-catalyzed reaction conditions in CH(2)Cl(2). Formation of alkoxylactones by an in situ derivatization of adducts was also observed.

Robust mixed 10/12 helices promoted by "alternating chirality" in a new family of C-linked carbo-beta-peptides.

The C-linked carbo-beta-peptides, oligomers of a new class of C-linked carbo-beta3-amino acids, have been shown to generate mixed 12/10 and 10/12 helices. The design involves use of "alternating chirality" of the epimeric (at the amine center) monomers to control the stability of these helices. The observation of stable 12/10 helix in a tripeptide and 10/12 helix in a tetrapeptide is unprecedented.

Zirconium(IV) chloride catalyzed new and efficient protocol for the selective cleavage of p-methoxybenzyl ethers.

A highly selective and efficient method for the unmasking of p-methoxybenzyl (PMB) ethers and esters has been developed by use of 20 mol % of zirconium(IV) chloride as Lewis acid in acetonitrile. The present method is very fast, and the conditions are tolerable to a variety of acid/base-sensitive protecting groups and substrates such as carbohydrates, terpenes, and amino acids. The products are obtained in good to high yields.