Fischer Carbene Catalysis of Alkynol Cycloisomerization:  Application to the Synthesis of the Altromycin B Disaccharide

Abstract

The tungsten-catalyzed cycloisomerization of alkynyl alcohols can be conducted without using photochemistry, using a stable tungsten Fischer carbene as the precatalyst for this transformation. A variety of alkynyl alcohols undergo cycloisomerization under these conditions to provide endocyclic enol ethers of 5, 6, and 7-membered ring sizes. The utility of this method is further demonstrated in the stereoselective synthesis of the disaccharide substructure of altromycin B.The importance of cyclic enol ethers in synthetic organic chemistry has been demonstrated in several contexts, including the efficient synthesis of a variety of biologically important carbohydrate and oligosaccharide-containing natural products, in which carbohydratederived cyclic enol ethers (glycals) are valuable electrophilic partners for a variety of glycoside synthesis processes. 1 Our laboratory has developed group VI transition metalcatalyzed processes for the synthesis of structurally diverse carbohydrates arising from noncarbohydrate-derived alkynyl alcohols, which has greatly expanded the scope of available substrates for glycal-based approaches to glycoconjugate synthesis. 2 The various methods reported by our laboratory for catalytic cycloisomerization have utilized photochemical activation of molybdenum or tungsten carbonyl in the presence of a tertiary amine, with molybdenum catalysis preferred for the formation of five-membered rings 3 and tungsten catalysis proving more effective for the synthesis of six 4 -and seven-membered ring cyclic enol ethers 5 (Figure 1). However, we are aware that the requirement for photochemical activation has limited the exploration and application of this methodology to laboratories that have specialized photochemical equipment. Thus we describe herein a new catalytic system which does not require photochemical activation, based on (methoxymethylcarbene)pentacarbonyl tungsten (3) 6 as a stable and easily prepared precatalyst for the Correspondence to: Frank E. McDonald, fmcdona@emory.edu. Supporting Information Available: Experimental procedures, characterization and spectral data on new compounds. This material is available free of charge via the Internets at http://pubs.acs.org. Fischer carbene-catalyzed cycloisomerizations of alkynyl alcohols 20 with C3 and C4-oxygen substituents 9b required additional optimization relative to the photochemical procedure (Table 2), as substantial amounts of the exocyclic glycal were produced from substrate 20b. As reported by others, 15 sterically bulky propargylic substituents are required for high endo-regioselectivity, but we observed that reduced steric bulk in the O4 methoxymethyl (MOM) protective group required increasing the steric bulk at O3 to the triisopropylsilyl ether 20c to obtain good endo-regioselectivity. The formation of exocyclic glycal 22b from substrate 20b was rationalized as the action of tungsten pentacarbonyl as a Lewis acid to promote cyclization to 25 (figure 2), but increasing the steric bulk at O3 in substrate 20c would increase...

Effect of CO substitution on the redox properties of Fischer Mo(0) carbene complexes Mo(CO)5=C(Y)(2-Furyl), Y=OEt, NHCy or NH2

“…Fischer-type complexes are valuable species in organic syntheses and in catalytic processes [11,12,13] and knowledge of the redox properties of these complexes may lead to a better understanding of factors influencing the catalytic activity of these complexes. It is well established that both the carbene ligand substituents, i.e.…”

The Tandem Ring‐Closing Metathesis–Isomerization Approach to 6‐Deoxyglycals

“…[14][15][16] While most glycal syntheses rely on reductive elimination of glycosides in one way or the other, [17,18] over the past few years transition metal mediated or catalyzed cyclization reactions became more and more important. In particular, the cyclization of alkynols [19][20][21] and the ring-closing metathesis [22][23][24] of enol ethers [25][26][27][28][29] has attracted considerable attention. The observation that the well established ruthenium-based metathesis catalysts sometimes catalyze other reactions with comparable efficiency [30,31] has not only stimulated research directed at a deeper understanding of the degradation reactions of these complexes, [32,33] but has also led to the development of new metathesis-non-metathesis tandem sequenAbstract: Protected 3,6-dideoxyglycals have been synthesized de novo as single isomers starting from ethyl lactate by using the tandem RCM-isomerization reaction as the key step.…”

Avanços Recentes Na Química Dos Aminoaçúcares: Ocorrência, Biossíntese, Síntese E Aplicação

“…Os produtos de partidas utilizados nestas reações de síntese são 1,2-glicais ou glicosídeos 2,3-insaturados protegidos, [87][88][89][90][91] é, análogos de açúcar contendo uma ligação dupla. A adição de reagente(s) apropriado(s) a essa ligação deve resultar na formação de ligações C-NH 2 e C-OH nos dois átomos de carbono vizinhos, ligados por uma dupla ligação (Esquema10).…”