Cyclic amino ethers

The second type of cyclodehydration to be presented is the formation of cyclic enol ethers and cyclic enamines. Here, an alcohol or amino group reacts with an enol, resulting in ring closure with loss of H20. Such reactions... 

Under oxidation conditions, a C—C double bond can be functionalized by either two alkoxycarbonyl groups or one alkoxycarbonyl group and one heteroatom. As shown in Scheme 4.14, two ester groups are successfully introduced to styrene in an enantioselective manner, producing a phenylsuccinic ester using a Pd/MeO-BIPHEP complex. mcw-Diols are converted into cyclic ethers in an asymmetric manner when catalyzed by Pd/chiral bisoxazoline. Intramolecular aminopallada-tion followed by carbomethoxylation gives an cyclic amino ester in moderate ee when catalyzed by a Pd/bis(isoxazoline) complex. " ... 

Chiral macrocyclic amino-ethers have been prepared recently (69). Ligands of type E are obtained by attaching a chain (or two chains, one at each Z center to the type D macrocycles (81). The synthesis of macro-cyclic peptides will not be discussed here. 

Radical cyclizations are often used in ring formations and are an effective methodology in the synthesis of piperidines. The intramolecular cyclization of an oxime ether, such as 63 onto an aldehyde or ketone gives a new entry into cyclic amino alcohols <99JOC2003, 99H(51)2711>. Similarly, reaction of a terminal acetylene with BujSnH generates a vinyl radical, which will cyclize with an imine moiety to give 3-methylenepiperidine <99TL1515>. The indolizidine alkaloid ipalbidine was prepared by a sulfur-controlled 6-exo-selective radical cyclization of an a/p/ia-phenylthio amide <99H(50)31>. 

In the condensation of diols, halogenated alcohols, amino alcohols, cyclic hydroxy ethers, or other bifunctional hydroxy compounds with carbodiimides, 5-, 6-, and 7-membered 1,3-O-N- or l,3-7V,7V-heterocyclics are obtained [14]. 

Table 2 contains some examples of TTN oxidative coupling reactions. These examples show that the reaction can often tolerate unprotected amino add side chains, and that both 14- and 17-membered cycloisodityrosines can be obtained. In addition, the TTN oxidative coupling has been employed in the formation of 16-membered cyclic biaryl ethers of the type found in vancomycinJ20,21 The drawbacks of TTN oxidative coupling are the low yields, the formation of byproducts, and the need for additional transformations to arrive at the cycloisodityrosine target. 

Cyclic amino-carbenes, in molybdenum carbonyls, 5, 457 Cyclic bis(phosphine) dichlorides, with iron carbonyls, 6, 48 Cyclic carbenes, as gold atom ligands, 2, 289 Cyclic carbometallation, zirconium complexes, 10, 276 Cyclic carbozirconation characteristics, 10, 276 intermolecular reactions, 10, 278 intramolecular reactions, 10, 278 Cyclic dinuclear ylides, and gold , 2, 276 Cyclic 1,2-diols, intramolecular coupling to, 11, 51 Cyclic enones, diastereoselective cuprate additions, 9, 515 Cyclic esters, ring-opening polymerization, via lanthanide catalysis, 4, 145 Cyclic ethers... 

Cyclic a-amino acids J The unsaturated inline 1, prepared as shown, on treatment with TMS triflate (1 equiv.) cyclizes to a mixture of trans- and cis-2, with marked preference for the former cyclic amino acid. The selectivity is dependent on the solvent. It is highest (33 1) in toluene, but the highest yield (55%) and cleanest reaction is obtained in r-butyl methyl ether even though the diastereoselectivity is lower (18 l). Lewis acids do not initiate this cyclization. 

Entry 9 in Table 15 illustrates another synthetically useful stereocontrolled reduction of cyclic oxime ethers (isoxazolines) to alicyclic amino alcohols using LAH. The stereoselectivity obtained is further enhanced by the incorporation of a 4a-hydroxy group which, upon reduction, affords almost entirely the erythro isomer (equation High diastereoselectivity in the reductive cleavage of isoxazolines has... 

Amino nitriles are useful for conjugate addition Acyl anion equivalents of the ester d1 synthon - C02R Methods Based on Vinyl (Enol) Ethers and Enamines Lithium derivatives of cyclic vinyl ethers The synthesis of pederin and related anti-tumour agents Lithium derivatives ofallenyl ethers Oxidative Cleavage of Allenes... 

New preparative syntheses of 6-0-(2-amino-2-deoxy-a-D-glucopyranosyl)-D-chiro-inositol 1-phosphate and a 1,2-cyclic phosphate derivative have been reported. Differential protection was achieved by initially locking the four equatorial hydroxyls of D-c/iiro-inositol as cyclic Tipds ethers and then generating a ci5-epoxide from the two remaining trans-diaxial hydroxyls under Mitsunobu conditions. Lewis acid catalysed trans-diaxial opening with allyl alcohol allowed for selective protection at 0-1 and 0-6. ... 

C7H15NO5 193.199 Formerly represented as cyclic anhydro ether. Struct, revised to acyclic form in 1990. Constit. amino acid of Galantin I. Cryst. (MeOH aq.). 

In this case, there will be perfect stereospecificity with the configuration of the ether bond (see circle) determining the configurations of the sp -center generated. When this procedure is applied to cyclic amino alcohols, it opens the road to non-natural amino acids [141]. 

Gallagher et al. reported on various IV-heterocycle construction via cyclic sulfamides. Using this strategy, they synthesized enantiopure 1,4-benzoxazine 311, which was the precursor of the blockbuster antibiotic levolloxacin 312 (Scheme 40.67). Starting from Boc-protected amino alcohol 305, sulfamidate 306 was prepared using RuCU and NaI04. 306 was treated with halo phenol 308 followed by acidic hydrolysis to afford amino ether 310. The compound 310 underwent Pd-catalyzed C—N alkylative cyclization to produce benzoxazine 311, which was the potential precursor from which Levolloxacin 312 can be synthesized. 

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