Cyclization procedures

Thiazole acetic acids and their hotnologs can also be prepared by cyclization procedures 4-thiazole alkanoic acids and their salts were prepared by treating a thioamide with a -y-chloro- or 7-bromoacetoacetic or their a-alkyl derivatives (4, 10, 16, 22, 273, 275, 281, 640, 647, 695). 

Azetidine was first prepared in low yield and impure form in 1888 by treatment of 3-bromopropylamine with base (1888CB2669). Various modifications of the standard cyclization procedures have been reported (79CRV331), but by far the most efficient synthesis to date, which utilizes only readily available materials, is that outlined in Scheme 6. 

This cyclization procedure was conveniently applied to the preparation of the key intermediate of a five-step synthesis of ( )-muscone [48]... 

Similar 5-exo cyclization procedures have been widely utilized by Evans in his total syntheses of complex natural compounds, such as the synthesis of ionomycin [12a] and polyether antibiotic X-206 [12b]. A 5-exo cyclization of a y-epoxy alcohol has also been observed under basic conditions [12c]. 

An important cyclization procedure involves acid-catalyzed addition of diene-ketones such as 58, where one conjugated alkene adds to the other conjugated alkene to form cyclopentenones (59). This is called the Nazarov cyclization Cyclization can also give the nonconjugated five-membered ring. ... 

B-Lactams.- The now standard intramolecular Wittig cyclization procedure has been used110,111 to prepare a number of... 

Scheme 3.5. Rare example of a domino radical ring expansion/cationic cyclization procedure.

Scheme 3.8. Domino radical cyclization procedure in the synthesis of lysergic acid derivatives.

Scheme 3.21. Domino radical macro-cyclization/transannular-cyclization procedure for the synthesis of the taxane skeleton.

Scheme 3.22. Domino radical cyclization procedure for the synthesis of [6.5.5] fused tricycle 3-87.

Scheme 3.27. General scheme of domino radical ring expansion/cyclization procedure.

Scheme 3.45. Domino radical ring-opening/cyclization procedure for the synthesis of spiroketone 3-171.

Scheme 3.62. Domino radical hydrogen abstraction-cyclization procedure in the synthesis towards Aspidosperma alkaloids.

Reaction of phenyl vinyl ketone with cyclopentanone under thermal conditions resulted in a diastereomeric mixture of 1,5,9-triketones 374 via a double Michael reaction. Treatment of this mixture with ammonium formate in polyethyleneglycol-200 under microwave irradiation conditions led to the very fast and efficient formation of a 2 1 diastereomeric mixture of cyclopental flquinolizidines 375 and 376 <2002T2189>. When this reductive amination-cyclization procedure was carried out starting from the purified /ra r-isomer of 374, the result was identical to that obtained from the cis-trans mixture, showing the operation of thermodynamic control (Scheme 86). 

Intramolecular C/H insertion by copper-catalyzed decomposition of a-diazoketones provides a convenient cyclization procedure which is limited, however, to diazo compounds which allow energetically favorable realization of the transition state leading to the cyclized product. 

The Heck reaction, a palladium-catalyzed vinylic substitution, is conducted with olefins and organohalides or pseudohalides are frequently used as reactants [15, 16], One of the strengths of the method is that it enables the direct monofunctionalization of a vinylic carbon, which is difficult to achieve by other means. Numerous elegant transformations based on Heck chemistry have been developed in natural and non-natural product synthesis. Intermolecular reactions with cyclic and acyclic al-kenes, and intramolecular cyclization procedures, have led to the assembly of a variety of complex and sterically congested molecules. 

Reactions of 1,2,4-thiadiazoles with radicals and carbenes are virtually unknown. Catalytic hydrogenations and dissolving metal reductions usually cleave the N-S bond in a reversal of the oxidative cyclization procedures used in synthesis of 1,2,4-thiadiazoles (see Section 5.08.9.4). 

Results concerning these ring systems are summarized in Scheme 52. Synthesis of a benzologue of the [l,2,3]tri-azolo[4,3-triazine ring system has been published by Abbott et al. <2002T3185>. The essence of the cyclization procedure is diazotation of the zwitterionic aminoaryltriazole compound 261, whereupon an internal azo coupling takes place to yield the fused triazine 262 in low yield (24%). 

In CHEC-II(1996) only one cyclization procedure was discussed in more detail <1996CHEC-II(8)445>. During the recent years, however, some basically new approaches were reported, and these are shown in Scheme 39. 

A unique cyclization procedure was conducted by Curran et al. in which they showed that axial chirality can be transferred into a new stereocenter with retention of chirality (Scheme 46) [136]. Substrates M or P-174a,b... 

Among the two cyclization procedures that utilize 2,2 -diaminobiphenyls, the Tauber synthesis has been most widely used and proceeds in higher yields than the diazotization reaction. The application of this method to the synthesis of carbazoles is limited by the availability of 2,2 -diaminobiphenyls. 

The molybdenum-catalyzed cyclization procedure works well for a variety of homoprogargylic alcohols to afford the cycloisomeric 2,3-dihydrofuran compounds, as shown in Table I. The transformation was originally discovered with the reagent arising from reaction of molydbenum hexacarbonyl and trimethylamine oxide, but catalyst turnover and product isolation yields are significantly improved with the cunent procedure, which... 

The previously unreported 1,2,3-thiadiazole-4-thiolate (33) was synthesized by an extension of Hurd and Mori s cyclization procedure <88JHC1873> in which methyl dithiopropionate was converted to intermediate (32). This was cyclized with thionyl chloride to the 1,2,3-thiadiazole and the protecting group removed to give thiolate (33) (Scheme 10). 

It was shown previously that saturated 5(4//)-oxazolones or 2-oxazolm-5-ones with only one substituent at C-4 can be considered as the tautomeric form of saturated 5(2//)-oxazolones or 3-oxazolin-5-ones. These compounds can also be considered as amino acid derivatives and, indeed, cyclization procedures are the most commonly used to prepare these compounds. The cyclization reaction employs a variety of cyclodehydrating agents and the general method is shown in Scheme 7.23, with an A-acyl-a-amino acid being the most typical starting material used. In this way, 5(4//)-oxazolones derived from most natural amino acids 99 (R3 = H) have been obtained by heating the corresponding A-acyl derivatives in the presence of acetic anhydride. 

In addition to the typical cyclization procedures described above, methods involving the use of other mild, cyclodehydrating agents have been published. For example, cyanuric chloride in the presence of triethylamine, 2-ethoxy-A-ethoxycarbonyl-l,2-dihydroquinoline (EEDQ) or 2-isobutoxy-A-isobutoxy-carbonyl-1,2-dihydroquinoline (IIDQ), ° A,A-dimethylchlorosulfitemethanimi-... 

Alternatively, if the dehydroamino acid is C-terminal or is central in the peptide chain, then the oxazolone precursor to the dehydropeptide must be in position two in order to apply this methodology (Scheme 7.165). The requisite unsaturated 5(4//)-oxazolone intermediate 518 is obtained from the appropriate precursors following standard cyclization procedures and avoiding experimental conditions that would epimerize the chiral center. This methodology has been applied to access analogues of important peptides including dehydroaspartame, somatostatin, and dermorphin. In these cases, a dehydroamino acid was incorporated into the peptide backbone to study the relationship between conformational restriction and biological properties of the modified peptide. 

The acetic acid-catalyzed cyclization procedure was adopted in a synthesis of the antifungal antibiotic piperazinomycin (86TL4481). The for-... 

Isopulegol can be isolated from this mixture and hydrogenated to (-)-menthol. The remaining isopulegol stereoisomers can be partly reconverted into (+)-citronellal by pyrolytic cleavage and reused in the cyclization procedure [79]. 

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