214477-37-9Relevant academic research and scientific papers
Stereoselective synthesis of fused bicyclic β-lactams through radical cyclization of enyne-2-azetidinones
Alcaide, Benito,Rodriguez-Campos, Ignacio M.,Rodriguez-Lopez, Julian,Rodriguez-Vicente, Alberto
, p. 5377 - 5387 (2007/10/03)
A convenient, stereoselective entry to racemic and enantiomerically pure fused bicyclic β-lactams has been developed that involves the radical- mediated cycloisomerization of easily available monocyclic enyne-β-lactams as the key synthetic step. These compounds are obtained provided that an activated double bond is present as a radical acceptor. In the absence of this condition, new forms of reactivity were observed, including C3-C4 bond cleavage of the β-lactam ring to yield tetrahydropyridine derivatives and 1,5-radical translocation to yield new bicyclic derivatives. Some simple transformations were tested on representative examples of the different types of bicyclic systems prepared to demonstrate their potential as intermediates in the preparation of other differently functionalized systems.
Alkyne-Co2(CO)6 complexes in the synthesis of fused tricyclic β- lactam and azetidine systems
Alcaide, Benito,Polanco, Concepcion,Sierra, Miguel A.
, p. 6786 - 6796 (2007/10/03)
A synthetic approach to racemic and enantiomerically pure, fused tricyclic 2-azetidinones and azetidines has been developed by using a Pauson- Khand (P-K) reaction on monocyclic enyne-β-lactams as the key synthetic step. The access to cyclization precursors, monocyclic β-lactams 1-7, was achieved by Staudinger reaction of enyne imines 8 and 9 and D-glyceraldehyde imines 10 and (benzyloxy)- or phenoxyacetyl chlorides. Enyne imines 8 and 9 formed cis-2-azetidinones 1 and 2 having the required enyne moiety. cis-2- Azetidinones 11 were obtained as single diastereomers and transformed to enyne-2-azetidinones 3 and 5 by standard methodology. Alternatively, 4- formyl-2-azetidinones 14 were prepared by cyclization of p-anisyl glyoxal diimine and (benzyloxy)acetyl chloride and converted to racemic enyne-β- lactams 4 and 6 by standard reactions. Enyne-2-azetidinones 1-7 were reacted with Co2(Co)8 to quantitatively yield the corresponding alkyne-Co2(CO)6 complexes. Reaction of such complexes with different promoters, especially heat and TMANO, formed tricyclic 2-azetidinones 15-19 with the ring system fused to the C3-C4 and C4-N1 lactam bonds. Yields were usually high, and the processes were highly diastereoselective. The exceptions were enyne-2- azetidinones 2 and 3a bearing N-propargyl moieties. These products decomposed to mixtures of unidentifiable products. Inhibition of the amide resonance was postulated as responsible for the failure of β-lactams 2 and 3a to form tricyclic systems. In fact, the analogous enyne-azetidines 20a,b smoothly cyclized to form the corresponding tricyclic systems. This approach to tricyclic azetidines was extended to prepare different products. A new, unprecedented, N1-C2 bond breakage was also observed in the azetidine ring. The results described show that the P-K reaction is a suitable approach to tricyclic 2-azetidinones and azetidines. These are the first examples reported for a P-K reaction in with the enyne system is tethered to a strained heterocyclic four-membered ring.
