Chiral acetals asymmetric cyclization

Bartlett PA, Johnson WS, Elliott JD (1983) Asymmetric synthesis via acetal templates. 3. On the stereochemistry observed in the cyclization of chiral acetals of polyolefinic aldehydes formation of optically active homoallylic alcohols. J Am Chem Soc 105 2088-2089... 

Aside from the type III cyclizations described above, acetals have seen limited use in intermolecular Prins reactionsand extensive use as initiators for cation-alkene cyclizations.Only limited success has been achieved in Lewis acid catalyzed addition of acetals to alkenes. Better success has been achieved in the synthesis of C-glycosides by Lewis acid catalyzed addition of glycosyl acetates or glycals to alkenes. Johnson has extensively developed the use of acetals as initiators for cation-alkene cyclizations. Recent studies have shown that excellent asymmetric induction can be obtained using chiral acetals derived from optically active 2,3-butanediol or 2,4-pentanediol. - ... 

The feasibility of cyclizing polyenes with iminium ion initiators has received only scant attention. 72 Cyclization of imine (77) under aprotic conditions with SnCU affords predominantly rran -decalins containing endocyclic unsaturation. This mixture was deduced by H NMR analysis to contain diastereomers (78) to (81) in the indicated abundances as depicted in equation (7). The extent of asymmetric induction in forming the decalin ring system (9S,10iS 9/ ,10/ = 61 39) is significantly lower than that of related cyclizations of chiral acetal substrates. ... 

Enamines of cyclohexylamine have been enantioselectively cyclized to bicyclo[3.3.1] nonanedione systems, using acryloyl chloride and chiral pyrrolidine catalysis. Enantio-pure A-sulflnylimines have been used in asymmetric synthesis of isoquinolone alkaloids, and a stereocontrolled synthesis of 3,4,5,6-tetrahydropyrimidine-based amino acids from imino ethers has been reported. Diastereoselective additions of chiral acetals of (2-lithiophenyl)acetaldehyde to arylimines have been used in an asymmetric synthesis of 1-aryltetrahydroisoquinolines. " Organolithiums react with chiral imines, in the presence of Lewis acids or bases, to give amines in up to 100% de. Diastereoselective additions of copper reagents to imines derived from (5)-l-phenylethylamine have been reported. 

An asymmetric synthesis of ethyl 2,3-dideoxy-4-C-methyl-3-C-methylene-D-g/ycero-pentofuranosides has been described. Thus, regioselective cyclization of the chiral acetal 62 (derived from 2,3-dimethyl-2-butenal) under acidic conditions. 

A similar strategy served to carry out the last step of an asymmetric synthesis of the alkaloid (—)-cryptopleurine 12. Compound 331, prepared from the known chiral starting material (l )-( )-4-(tributylstannyl)but-3-en-2-ol, underwent cross-metathesis to 332 in the presence of Grubbs second-generation catalyst. Catalytic hydrogenation of the double bond in 332 with simultaneous N-deprotection, followed by acetate saponification and cyclization under Mitsunobu conditions, gave the piperidine derivative 333, which was transformed into (—)-cryptopleurine by reaction with formaldehyde in the presence of acid (Scheme 73) <2004JOC3144>. 

In fact, the role of copper and oxygen in the Wacker Process is certainly more complicated than indicated in equations (151) and (152) and in Scheme 10, and could be similar to that previously discussed for the rhodium/copper-catalyzed ketonization of terminal alkenes. Hosokawa and coworkers have recently studied the Wacker-type asymmetric intramolecular oxidative cyclization of irons-2-(2-butenyl)phenol (132) by 02 in the presence of (+)-(3,2,10-i -pinene)palladium(II) acetate (133) and Cu(OAc)2 (equation 156).413 It has been shown that the chiral pinanyl ligand is retained by palladium throughout the reaction, and therefore it is suggested that the active catalyst consists of copper and palladium linked by an acetate bridge. The role of copper would be to act as an oxygen carrier capable of rapidly reoxidizing palladium hydride into a hydroperoxide species (equation 157).413 Such a process is also likely to occur in the palladium-catalyzed acetoxylation of alkenes (see Section 61.3.4.3). 

Permanganese is a common oxidative reagent, the application of which to the asymmetric oxidative cyclization of 1,5-dienes has been reported by Brown (Scheme 3.14). The addition of acetic acid is quite important for the reaction to proceed, and highly functionalized tetrahydrofurans are obtained in a range of 58 to 75% ee, in diastereoselective manner [35]. Another oxidative transformation using KMn04 with a chiral ammonium salt has been investigated. Scheme 3.15 illustrates the asymmetric dihydroxylation of electron-deficient olefins to chiral diols in the... 

Chiral pybox ligands were synthesized as ligands for the asymmetric cyclopropanation of styrene.10 In-pybox ligand 3 was prepared by reaction of 1 with 2,6-pyridine dicarbonyl dichloride in the presence of potassium hydrogen carbonate in isopropyl acetate followed by cyclization of the fcA-hydroxyamide with BF3 OEt2 at 120°C.22... 

They can also be used as vinylic carbanion species as shown by the asymmetric synthesis of the chro-man ring of vitamin The (E)/(Z) mixture of chiral sulfoxide (9) was readily isomerized into the ( )-isomer with LDA in THF (the exclusive formation of the ( )-isomer was due to the chelation of lithium with an oxygen of the acetal). Condensation to trimethylhydroquinonecarbaldehyde gave only one diastereoisomer and then the cyclization in presence of sodium methoxide was also fully stereoselective (the stereochemistry of the cyclization being controlled by that of the allylic hydroxy group which is eliminated during the cyclization Scheme 48). 

Diastereoselective asymmetric oxidative cyclization of m-l,2-divinylcyc ohexane is achieved if chiral carboxylic acids are employed as nucleophiles instead of acetic acid 2l 22 8b. Addition of various types of molecular sieves has a decisive influence on the oxidative cyclization of m-1,2-di-vinylcyclohexane, resulting in enhanced diastereoselectivities (up to 62 %), as well as in opposite absolute configuration [(lS,3a/, 7a5 ) or (l/ ,3aS.7a7 )] of the newly created centers in aryl-sub-stituted hexahydro-3-methylene-l-(l-oxo-2-phenoxypropoxy)indans 921. The origins of these effects, although not without precedence, are unclear. 

The intramolecular cyclization route to a specific P-lactam often depends on the availability of a P-aminoester having the required stereochemistry. A review which considers the asymmetric synthesis of p-aminoesters is available (94MI475). Ytterbium promoted addition of benzylamine to 2-alkenoic esters having a stereogenic centre at the y-position (94CL827) and triphenyl borate mediated reaction of chiral imines with silylketene acetals have been utilised to give P-aminoesters stereoselectively (93BMC2337). 

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