The allene moiety represents an excellent partner for the [2+2] cycloaddition with alkenes and alkynes, affording the cyclobutane and cyclobutene skeletons in a single step. This strategy has been widely studied under thermal, photochemical and microwave induced conditions. More recently, the use of transition metal catalysis has been introduced as an alternative relying on the activation of the allenic component. On the other hand, the intramolecular version has attracted much attention as a strategy for the synthesis of polycyclic compounds in a regio- and stereoselective fashion. This critical review focuses on the most recently developed [2+2] cycloadditions on allenes along with remarkable early works accounting for the mechanism, the regio- and diastereoselectivity of the cycloadducts formed (103 references).

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Exploiting [2+2] cycloaddition chemistry: achievements with allenes

Cyclobutanones and Cyclobutenones in Nature and in Synthesis [New Synthetic Methods(71)]

Tetrodotoxin, a toxic principle of puffer fish poisoning, is one of the most famous marine natural products because of the complex structure having many functional groups and its potent biological activity leading to death. Since the structure elucidation in 1964, this toxin has been recognized as a formidable target molecule for total synthesis. We have recently achieved the first asymmetric total synthesis from 2-acetoxy-tri-O-acetyl-d-glucal as a chiral starting material. The highly hydroxylated cyclohexane ring was constructed by Claisen rearrangement and regioselective hydroxylations of an acetone moiety and an intramolecular directed aldol condensation of the precursor having methyl ketone with dihydroxyacetone, which was synthesized through Sonogashira coupling. Installation of nitrogen functionality was unsuccessful through an attempted Overman rearrangement. We, therefore, employed a new intramolecular conjugate addition strategy between the carbamate and unsaturated ester groups. The alpha-hydroxyl lactone moiety was synthesized through an intramolecular epoxide opening by the Z-enolate of aldehyde, which was followed by oxidation-reduction of the resulting cyclic vinyl ether. The lactone was then converted to a protected ortho ester, and then gunanidinylation was followed by cleavage of the 1,2-glycol to give the fully protected tetrodotoxin. Selection of the protective groups has finally led us to accomplish the total synthesis of tetrodotoxin in an enantiomerically pure form. All the stereogenic centers were controlled with high selectivity, and the hydroxyl groups were differently protected to discriminate for the future analogue synthesis of a bioorganic program. The synthetic tetrodotoxin was purified by ion exchange chromatography and characterized to be identical with the natural compound.

First Asymmetric Total Synthesis of Tetrodotoxin

Synthetic applications involving halogenated ketenes

2-Substituted furans 1a,b,c were found to be conveniently transformed into trans 4-oxo-2-enals 2a,b,c in 62−87% yields by using NBS/pyridine in THF−acetone−H2O (<−15 °C then rt) or NBS/NaHCO3 in acetone−H2O (<−15 °C then rt after addition of pyridine). Further oxidation of the enals 2a−c using NaClO2 led to the trans 4-oxo-2-enoic acids 3a−c in good yields. With this transformation in mind, we designed syntheses of (+)-aspicilin, (+)-patulolide, and (−)-pyrenophorin. In the synthesis of (+)-aspicilin as shown in Schemes 1 and 2, the pivotal intermediate 6 was prepared from olefin 7 in which 2-furyl group is attached. The AD reaction of 7 secured the C(5) and C(6) stereochemistry of aspicilin, and the subsequent transformation using the protocol described above afforded the ester 6. Stereocontrolled reduction of 6 followed by deprotection and the Yamaguchi macrocyclization furnished (+)-aspicilin. For the synthesis of (+)-patulolide (Scheme 3) and (−)-pyrenophorin (Scheme 4), the intermediates are the fura...

Efficient Conditions for Conversion of 2-Substituted Furans into 4-Oxygenated 2-Enoic Acids and Its Application to Synthesis of (+)-Aspicilin, (+)-Patulolide A, and (-)-Pyrenophorin.

Arvind D. Patel

Papers

Synthesis and properties of 2'-deoxy-2'-thiocytidine

Synthesis of properties of 2' deoxy 2' thio cytidine

Halogenated ketenes. XXIV. Cycloaddition of alkylhaloketenes and methylenecycloalkanes. Spiro compounds

Halogenated ketenes. XXV. Cycloadditions with allenes

Decarboxylation of halogenated 2-oxetanones