1‐Oxa‐3‐cyclooctin

Abstract

1‐Oxa‐3‐cyclooctyne According to an MNDO calculation, 1‐oxa‐cyclooctyne (13) and 1‐oxa‐3‐cyclooctyne (14) are 8‐membered heterocyclic ring systems with high steric energy (ring strain). On the basis of THF (1) and acetoacetic ester (4), a multi‐step synthesis is described for 14. The triple bond is introduced in the last step by a thermal fragmentation of the 1,2,3‐selenadiazole 12.

Synthesis of Medium‐Sized 2,ω‐cis‐Disubstituted Cyclic Ethers by Reductive Cyclization of Hydroxy Ketones

“…Taking into account the preferred boat‐chair low energy conformations of oxocane derivatives, the boat‐chair like conformation shown for B in Scheme , must be the most stable and reactive, since the hexyl substituent (R=Hex) is adopting a favourable pseudoequatorial disposition. Evolution of this reactive conformer through the axial approach of Et 3 SiH, would be favoured because of the incipient formation of a more stable transition state with a boat‐chair‐like conformation, preferred both on steric and stereoelectronic grounds . Taking into account that the stereoselectivity of the reductive cyclization of 9‐hydroxy‐3‐pentadecanone 12 was similar to the previously observed from the isomeric 13‐hydroxy‐7‐pentadecanone 5 , we can conclude that the exchange of the substituents in the cyclic intermediate B had no influence in the reactive conformation and, as a consequence, on the stereoselectivity of the reductive cyclization.…”

Useful Designs in the Synthesis of Trans-Fused Polyether Toxins

“…Another successful contribution in line with this strategy, giving efficient access to six-, seven-, and eight-membered cyclic ethers, is the rhodium car-benoid-mediated cyclization of hydroxy a-diazo /?-keto esters. [89][90][91][92][93][94][95][96][97][98] The diazo alcohol intermediate 195 readily loses nitrogen upon treatment with catalytic amounts of rhodium(II) salts, usually dirhodium tetraacetate, in dichloromethane or refluxing benzene, and cyclic ethers 196 are formed in good yields (Scheme 12). Although the reaction formally requires an intramolecular insertion into the O-H bond, the mechanism of medium ring ether formation can be regarded as a nucleophilic attack by the hydroxy group on the highly electron-deficient rhodium carbenoid intermediate, generated by Rh(ID-catalyzed loss of nitrogen from the diazo compound.…”

Product Class 27: Selenazoles and Tellurazoles Containing One or More Other Heteroatoms

“…[22][23][24] This last aspect has been of particular interest in the context of strained cycloalkynes and the selenadiazole method has allowed access to cyclooctyne, [25] cycloheptyne, cyclohexyne, and cyclopentyne, [26] 3-thiacyclooctyne, [27,28] E-cycloundec-1-en-3yne, [29] cyclodeca-1,6-diyne, [30] 9-oxabicyclo[6.1.0]non-2-yne and 9-oxabicyclo[6.1.0]non-3yne, [31] 4-oxacyclooctyne, [32] a range of C 9 -C 12 cycloalkadiynes, [33] and 4-and 5-hydroxycyclooctyne. [22][23][24] This last aspect has been of particular interest in the context of strained cycloalkynes and the selenadiazole method has allowed access to cyclooctyne, [25] cycloheptyne, cyclohexyne, and cyclopentyne, [26] 3-thiacyclooctyne, [27,28] E-cycloundec-1-en-3yne, [29] cyclodeca-1,6-diyne, [30] 9-oxabicyclo[6.1.0]non-2-yne and 9-oxabicyclo[6.1.0]non-3yne, [31] 4-oxacyclooctyne, [32] a range of C 9 -C 12 cycloalkadiynes, [33] and 4-and 5-hydroxycyclooctyne.…”

“…[37,38] The synthesis of 1,2,3-selenadiazoles by reaction of semicarbazones with selenium dioxide in acetic acid was the original method introduced in 1970, [22][23][24] and has since been widely applied to synthesis of 4-aryl-, [36] 4-arylalkyl-, [39] 4-styryl-, [40] 4-cyclopropylsulfonyland 4-pyrazolylsulfonyl-, [41] 5-arylsulfonyl-, [35,37,42] 5-carbamoyl-, [43] cycloalkene-fused, [44,45] phenanthro-fused, [46] steroid-substituted, [47] and bis-1,2,3-selenadiazoles. [25][26][27][28][29][30][31][32][33][34] Since the target selenadiazoles are designed to undergo ready extrusion of selenium and nitrogen, they are somewhat unstable and care must be taken to use mild conditions in their preparation. [24] Scheme 25 Synthesis of 1,2,3-Selenadiazoles in Acetic Acid [24] (48); Typical Procedure: [24] To a stirred suspension of acetaldehyde semicarbazone (65 g, 0.64 mol) in AcOH (500 mL) at rt was gradually added finely powdered SeO 2 (71 g, 0.65 mol).…”