Syntheses of Cyclobutanones

These reagents were introduced, respectively, by Meyers [305], Oshima [306], Trost [307] and Corey [308], and skillfully applied as shown in the syntheses of cyclobutanones [307] and a-unsaturated aldehydes [308], in which the initially formed carbon-carbon bond was the first step of the overall synthetic schemes elaborated. 

Some miscellaneous ring enlargement reactions are presented in Scheme 11/13 two of them are syntheses of cyclobutanones, 11/90 and 11/92 [71] [72]. 

Several comparative procedures are included. The formation of 1-BENZYLINDOLE and GERANYL CHLORIDE by two different procedures are representative. An interesting comparison of three of the recent adaptations of the Claisen rearrangement on the same substrate is presented in the preparations of N.N-DIMETHYL-5/ -CHOLEST-3-ENE-5-ACETAMIDE, ETHYL-5/S-CHOLEST-3-ENE-5-ACETATE, and 5/9-CHOLEST-3-ENE-5-ACETALDEHYDE. For the utility of the procedure itself as well as for comparison with previously presented syntheses, the preparation and use of triflates in the synthesis of CYCLOBUTANONE is included. 

For example, 1-donor-substituted cyclopropancmethanols may be efficiently produced by cyclopropanation of suitably substituted enol ethers, by reaction of 1-donor-substituted 1-lithio-cyclopropanes with carbonyl compounds, or by addition of carbon nucleophiles to 1-donor-substituted cyclopropanecarbaldehydes. Oxaspiropentanes, important precursors of cyclobutanones, may as easily be obtained by epoxidation of methylenecyclopropanes, or by reaction of carbonyl compounds with diphenylsulfonium cyclopropanide and l-bromo-1-lithiocyclopropanes, respectively. Moreover, as the stereochemistry of most rearrangements may be efficiently controlled, asymmetric syntheses begin to appear. 

A considerable number of electrophiles were used, and the dithiane route found great utility for the syntheses of simple monofunctional compounds as well as for polyfunctional molecules, for which the dithiane moiety affords an invaluable temporary protection of a future carbonyl group. Some experimental procedures published in Organic Syntheses — cyclobutanone [277] and 3-hydroxy-l-cyclohexene-l-carboxaldehyde [278] — are illustrative. A similar route to aldehydes [279] makes use of sym-trithiane as a formyl anion equivalent. 

There have been three reported syntheses of 1,2-diazocines by means of ring-expansive cycloaddition reactions. In the first case, Sasaki and coworkers reacted 4,4-dimethyl-3,5-diphenylisopyrazole 25 with diphe-nylcyclopropenone to obtain diazocine 26 (73SC249). The second cycloaddition was achieved by Haddadin et al., who condensed cyclobutanone with tetrazine 27 (Ar = Ph) to afford diazocine 28 (Ar = Ph, X = O) or 29, depending on whether methanolic base or diethylamine was used as catalyst (84TL2577). A similar reaction was used to prepare a triazocine see Section IV,A,1. 

Hsiao, C.-N. et al. Efficient Syntheses of Protected (2S,3S)-2,3-Bis(hydroxy-methyl)cyclobutanone, Key Intermediates for the Synthesis of Chiral Carbocyclic Analogues of Oxetanocin. 4.1 1990 [127]... 

Oxaspiropentanes have been synthesized by the epoxidation of methylenecyclo-propanes with peracetic49), peroxybenzimidic 50), with p-nitroperbenzoic46) and m-chloroperbenzoic acid51). The parent oxaspiropentane 95, a convenient precursor of cyclobutanone 46was obtained from the peracid oxidation of a methylene chloride solution of methylenecyclopropane 94, Eq. (27)46,51). 

The key synthetic steps in the formation of the desired unnatural amino acids, 5-8, involved the preparation of appropriately substituted cyclobutanones followed by a Btlcherer-Strecker amino acid synthesis.12 The syntheses of the boron-containing amino acids were initiated utlizing alkenes 16 -19. Alkene 17 was prepared by a SN2 displacement of bromide from 4-bromobenzyl bromide (Scheme 3). In the syntheses of alkenes 18 and 19, a catalytic... 

Argon. An Organic Syntheses procedure for the dialkylation of 1,3-dithiane with 1 -bromo-3-chloropropane, as a first step in the synthesis of cyclobutanone, specified that argon, if available, be used as the inert gas in preference lo nitrogen because of its greater density. ... 

If the hydroxyalkyl function and the oxy substituent are linked to the same cyclopropane carbon, the pattern is perfect for a cyclopropylcarbinyl-cyclobutanone rearrangement. This allows a very convenient access to cyclobutanones (equation The method was used in syntheses of grandisol poitediol and... 

The photoisomerization of cyclobutanones to transient car-benes has been used as part of an interesting synthesis of muscarine (Pirrung and DeAmicis). Intramolecular oxetan formation has been used as part of novel syntheses of medium-ring ethers (1) and the tricyclo-octane (2) (Carless et al. Gleiter and Kissler). Cossy et al. have employed the photoreductive cycliza-... 

A number of nonbiogenetic total syntheses of dactylol in both racemic and optically pure forms have appeared in literature. The first example is the work reported in 1986 by Gadwood and eo-workers. (Scheme 3). This synthesis began with the eonversion of enone 5 into cyclobutanone 6. The cyclooctanoid framework was constructed using an oxy-Cope... 

Other syntheses of enaminones with unusual structures include reduction of vinylpyridinium salts [89JCR(S)112], addition of secondary amines to acetylenic ketones [72JCS(P1)80S], rearrangements of a-aminoalkylidene- 8-alkoxy a-lactams (80JOC936), and nucleophilic amination of perchloro-cyclobutanone (80AP959). 

Total syntheses of racemic muscarine and allomuscarine were achieved by Pirrung and DeAmicis 11), who used a new approach to formation of the stereoselectively substituted tetrahydrofuran nucleus (Scheme 8). The key step in this procedure was the stereospecific photochemical ring expansion of a cyclobutanone derivative. The cycloaddition of silyl enol ether with methylchloroketene generated by zinc dechlorination of 2,2-dichloropropionyl chloride followed by reductive removal of the halogen produced the methylsiloxycyclobutanone intermediate. Irradiation of the... 

In the case of cyclic a-halo ketones, ring contraction occurs. A similar reaction occurs on )0-halo ketones via the elimination of a hydrogen halide to cyclobutanone followed by the scission of cyclobutanone, known as the homo-Favorskii rearrangement.This reaction has been proved to be a useful tool for synthesizing the highly strained esters. 

The formation of cyclobutanones has been reported by Nawar and Le Tellier (1972 Le Tellier and Nawar, 1972a) and Dubravcic (1968). The cyclization reaction (Scheme 7.1) produces characteristic cyclobutanones derived from the fatty acids of the lipid. In recent years, as well as the well-known 2-dodecylcyclobutanone, 2-tetradecylcyclobutanone, 2-tetrade-cenylcyclobutanone and 2-tetradecadienylcyclobutanone have been found and synthesized in irradiated lipids, so the cyclization products of all main fatty acids has been observed. All the products are widely used to identify irradiated foodstuffs and to estimate the applied dose. 

The related Trost cyclobutanone annelation procedure, in which 1-lithiophenyl cyclopropyl sulphide is condensed with a cyclic ketone and the product rearranged with an acid catalyst, can be controlled to give considerable stereoselectivity and regiospecificity. Application to the methyladamantanone (321) permits specific syntheses of the two ketones (322a) and (322b) to be accomplished, and these have been used in the first experimental verification of the Front Octant Rule. ... 

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