Macrocyclization of Oxetane Building Blocks with Diazocarbonyl Derivatives under Rhodium(II) Catalysis

Abstract

Oxetanes, which are four-membered-ring cyclic ethers of type 1, are important building blocks in medicinal and natural product chemistry. [1] Oxetanes are useful reagents that undergo ring-opening [2] or ring-expansion [3] reactions because of a large ring strain (ca. 25 kcal mol À1 ) [4] and a high nucleophilicity of the O atom. [5] These derivatives react readily in the presence of Brønsted or Lewis acids to promote polymerization reactions. [6] Macrocyclizations, which, in principle, can be also afforded in these reactions, are rare. [7] In this context, we report the unusual Rh II -catalyzed condensation of oxetanes 1 and a-diazocarbonyls 2 that yields exclusively a rare type of functionalized 15-membered macrocycle 3 [Eq. (1)]. Interestingly, three oxetanes and one metal carbenoid intermediate condense in a one-pot process, and this under high concentration conditions (1m) and yields up to 84 %.

Oxetanes: Recent Advances in Synthesis, Reactivity, and Medicinal Chemistry

“…In particular, oxetanes react with diazo compounds, which can afford mixtures of products resulting from ring expansion and ylide formation with protonation or rearrangement. 531,532 In the 1960s, Nozaki et al 533,534 found that, when treated with a diazo compound in the presence of a chiral copper chelate, 2- Lacour and co-workers 540 described the formation of a number of interesting functionalized 15-membered macrocycles via Rh-catalyzed condensation of a single α-diazo-β-keto ester with three oxetane molecules (Scheme 148). The reaction proceeded under mild conditions at 20 °C, with catalyst loading of just 1 mol % Rh 2 (OAc) 4 and oxetane as the solvent, forming the macrocycle in yields up to 84%.…”

Regioselective and Enantiospecific Synthesis of Dioxepines by (Cyclopentadienyl)ruthenium‐Catalyzed Condensations of Diazocarbonyls and Oxetanes

“…For instance, under Cu catalysis,,,, or photochemical conditions, diazo reagents react with oxetanes in [4+1] processes to form substituted furans (Scheme a, [1,2]‐shift mechanism). On the contrary, under Rh(II) or Pd(II) catalysis, decompositions of α‐diazo‐carbonyls in the presence of oxetanes (solvent) afford 15‐membered macrocycles by [3+4+4+4] condensation (Scheme b). Recently, it has been shown that combinations of 1,10‐phenanthroline (phen) and [CpRu(CH 3 CN) 3 ][X] {X=PF 6 1a or X=BAr F , tetrakis[3,5‐bis(trifluoromethyl)phenyl]borate 1b } efficiently catalyze the decomposition of α‐diazo‐β‐keto esters and promote selective 1,3‐C–H insertions into THF and condensation reactions with ketones, lactones and cyclic carbonates .…”

“…[6] In fact, the high nucleophilicity of oxygenl one pairs [7] and the important ring strain ( % 25 kcalmol À1 ) [8] permit the facile formation of reactive oxonium ylide intermediates that decompose spontaneously into higher ring systems regio-and stereoselectively. On the contrary,u nder Rh(II) [11] or Pd(II) [9i] catalysis, decompositions of a-diazo-carbonyls in the presence of oxetanes (solvent) afford 15-membered macrocycles by [3 + + 4 + + 4 + + 4] condensation (Scheme1b). On the contrary,u nder Rh(II) [11] or Pd(II) [9i] catalysis, decompositions of a-diazo-carbonyls in the presence of oxetanes (solvent) afford 15-membered macrocycles by [3 + + 4 + + 4 + + 4] condensation (Scheme1b).…”