Carbonylation chemistry (carbon monoxide chemistry) has been the subject of extensive research in labo-scale organic syntheses as well as industrial processes, since it provides a powerful tool for the direct synthesis of a wide variety of carbonyl-containing compounds. However, the methods suffer from major disadvantages, including the high toxicity of carbon monoxide and difficulties in handling this gaseous reagent. The review describes innovative strategies to solve these drawbacks. The strategies should provide many synthetic organic chemists with experimentally simple and safe tools for carbonylation.
More than a thousand compounds possessing labdane and clerodane-type skeletons have been isolated from the natural sources, such as plants, marine products, fungi, and bacteria. These diterpenoids form big groups in secondary metabolites. Biogenetically, both the labdane and clerodane skeletons are derived from geranyl geranylpyrophosphate. However, their biological roles are not well known. This review describes current issues in research on labdane and clerodane-type diterpenoids, including the rearranged skeletons, related to their structural diversity and bioactivities. Synthetic challenges relevant to labdane and clerodane-type diterpenoids, an example of an enantiomeric labdane-type diterpene, and a recent genomic study of the biosynthesis of diterpenoids are also described.
Three approaches to biotin (1), i.e., the Cyanohydrin method and the Strecker methods I and II, have been investigated with L-cysteine as a starting material and the last one was found to be so efficient to be applied to a multi-kilogram-scale preparation. α-Amino aldehyde 46, which was readily derived from L-cysteine, was subjected to the Strecker reaction to afford syn-α-amino nitrile 47 with high diastereoselectivity and in high yield. The compound 47 was converted to amide 48 in high yield by applying Katritzky's protocol. Novel S, N-carbonyl migration of 48 and subsequent hydrolysis enabled clean conversion to 37 that is a precursor to a key intermediate 38 for 1. The Fukuyama coupling reaction of 38 with a zinc reagent by the use of our modified procedure employing heterogeneous Pearlman's catalyst allowed efficient installation of the 4-carboxybutyl chain. Short steps, high yield, and ease of operation of the present approach would permit the hitherto most efficient access to 1.
Development of odorless thiols [1-dodecanethiol (Dod-SH), 4-trimethylsilylphenylmethanethiol (TMSBM), 4-trimethylsilylbenzenethiol (TMSBT), and 6-morpholinohexanethiol (MHT)] and odorless sulfides [dodecyl methyl sulfide (Dod-S-Me), methyl 6-morpholinohexyl sulfide (MMS)] and their sulfoxides [dodecyl methyl sulfoxide (Dod-S (O) -Me), methyl 6-morpholinohexyl sulfoxide (MMSO)] as odorless substitutes for the foul-smelling ethanethiol, benzyl mercaptan, benzenethiol, and dimethyl sulfide (DMS) is described. They are conveniently applied for dealkylation, thiol exchange reaction, reductive ozonolysis, Corey-Kim oxidation, Swern oxidation, hydroboration, and reduction. The products of these reactions utilizing morpholine based thiol MHT, sulfide MMS and its sulfoxide MMSO can be easily purified by only acid-base extraction without involving chromatography, thereby eliminating unpleasant odors, saving time and protecting the environment. In view of current environmental and economic factors, the utility of these simple reagents could be enormously beneficial.
Michael addition reactions of various enolates derived from the selected ketone, ester, and amide toward γ-CH3-n, Fn-α, β-unsaturated ketones (n=13) were proved to smoothly furnish the desired 1, 4-adducts with the high level of si face selectivity which monotonously decreased by reduction of a number of fluorine. Although the Felkin-Anh model correctly anticipates the present stereochemical outcome only when E-acceptors were employed and the opposite stereoisomer was obtained from the corresponding trifluorinated Z-isomer, the hyperconjugative stabilization of transition states by electron donation from the allylic substituents (the Cieplak rule) successfully explains the π-facial preference of both E- and Z-acceptors at least in a qualitative manner.
The reaction of tertiary cyclopropanol systems with hypervalent iodines in a protic solvent caused oxidative bond cleavage at C1-C2 and C2-C3 leading to alkenoic acids or their corresponding esters in high yields. In the cases of the compounds bearing an alkyl group on the cyclopropane-ring, the endo-compound gave only the (Z) -alkene while the exo-compound afforded only the (E) -alkene. A strong acid catalyst promoted these reactions. In fluorinated alcohols, the oxidation of cyclopropanol systems with phenyliodine (III) diacetate caused a mixture of enones and β-acetoxyketones. On the other hand, phenyliodine (III) bistrifluoroacetate afforded alkenoic esters. The asymmetric synthesis of (-) -pinidine and its enantiomer was achieved by starting from norgranatanone via the asymmetric enolization, stereoselective cyclopropanation, and ring cleavage of the resulting cyclopropanol system with a hypervalent iodine as key steps. Formal asymmetric synthesis of (+) -indolizidine 223 AB was also accomplished.