This review focuses on total syntheses of garsubellin A, nemorosone and clusianone, which are polycyclic polyprenylated acylphloroglucinols (PPAPs). The PPAPs feature a highly oxygenated and densely substituted bicyclo[3.3.1]nonane core with prenyl, geranyl, and acyl side chains, and exhibit a wide range of biological activity, including cytotoxicity, antibacterial activity, HIV inhibitory activity, and antioxidant activity etc. These compounds have attracted the considerable attention of organic chemists due to fascinating chemical structures and intriguing biological activities. For total synthesis of this class compounds, several strategies were established and employed to construct a bicyclo[3.3.1]nonane core. Shibasaki-Kanai utilized stereoselective intermolecular aldol reaction, Claisen rearrangement and ring-closing metathesis. Danishefsky employed dearomative allylation, iodocarbocyclization, and bridgehead functionalization reactions. Simpkins and Marazano-Delpech used a Claisen-Deieckmann reaction with malonyl chloride. Porco group employed a double Michael reaction approach.
The silyl group acts as a directing group and a good leaving group in organic synthesis. We have been focusing on developing stereoselective synthesis utilizing these feature of silyl groups. In this context, stereoselective construction of multiple stereogenic centers using simple acylsilanes and transformation of cyclopropyl silyl ketones are described. The aldol-Tishchenko reaction of acylsilanes gives the corresponding 1,3-diol derivatives having three contiguous stereogenic centers with perfect levels of stereochemical control in one-pot. On the other hand, Mukaiyama aldol reaction of acylsilane silyl enol ethers derived from acylsilanes with dimethyl acetals affords the corresponding β-methoxyacylsilanes in high d.e.. The following 1,3-asymmetric induction in the nucleophilic addition furnished three diastereoisomers of 1,3-diol derivatives having the three contiguous stereogenic centers among four possible diastereomeric products with high stereoselectivity. Meanwhile, treatment of cyclopropylsilylmethanols derived from cyclopropyl silyl ketones with acid-catalyst gives the corresponding silyl-substituted homoallyl derivatives in high yields with good stereoselectivity. The protodesilylation of the resulting products proceeds with complete retention of the configuration.
Organophosphines play an important role in the field of organic synthesis, especially as ligands in transition metal catalysis. However, the synthesis of organophosphines with various functional groups still has many difficulties due to limitations in phosphorus-carbon bond formation. In this review, recent advances in the syntheses of organophosphines having various functional groups by using silylphosphines under mild conditions are described. Sterically protected silylphosphines are effectively applied to selective formations of several types of carbon-phosphorus bond, via three types of adequate activations; activation of a phosphorus-silicon bond of a silylphosphine by means of a fluoride, nucleophilic attack to the electrophile activated by a Lewis acid, and a transition-metal catalyzed activation of phosphorus-silicon bond. One successful application of a stepwise functional phosphine synthesis is also described.
Peridinin is known as a representative auxiliary light harvesting pigment for photosynthesis in the sea. In the peridinin-chlorophyll (Chl) a-protein (PCP) complex, exceptionally high (>95%) energy transfer efficiencies from peridinin to Chl a has been reported. This energy transfer efficiency is thought to be related to the unique structure of peridinin, which possesses allene and ylidenbutenolide functions and the unusual C37 carbon skeleton referred to as a ‘nor-carotenoid’. There are, however, no studies on the subjects of why peridinin possesses a unique allene group and an irregular C37 skeleton, and how these functions play a role in the exceptionally high energy transfer. We have established the highly efficient synthesis of natural peridinin and successfully synthesized its allene and conjugated polyene modified derivatives. Measurements of their ultrafast time resolved spectra and Stark spectra have strongly suggested that these structural feature of peridinin has essentially contributed to its super ability of energy transfer.
Crownophanes which were used as rotor molecules in this review were prepared via tandem Claisen rearrangement (TCR). Primary amines having a bulky end group were also prepared to use as a part of axle molecules. Using crownophanes, a new method to prepare rotaxane systems has been developed. That is, we call it “a method via covalent bond formation”. This method contains two processes, esterification and aminolysis. The first step is the reaction of hydroxy group of macrocyclic compounds (crownophanes) with acid chloride, and the second step is the reaction of the ester produced with amine having a bulky end group. This method successfully gave -, -, and rotaxanes in moderate yields. In the fluorescence spectrum, the efficient energy transfer from rotor molecules to end anthryl group of axle molecules was observed in the [n]rotaxanes. In the presence of lithium ion, the energy transfer occurred very efficiently, but not in the presence of other ions. Chiral recognition for phenylalaninol was also observed using achiral rotaxane having asymmetrical rotor and axle. We also reported that our rotaxanes could attach on the gold surface. We successfully observed the single rotaxanes by atomic force microscope. Thus, we report here that the rotaxane synthesis via covalent bond formation is successfully performed to give many kinds of rotaxanes starting from crownophanes which were prepared via TCR.
In this account, we focused on the high potentials of ruthenium hydride complexes, such as RuHCl(CO)(PPh3)3, as a multi-task catalyst for atom-economical C-C bond-forming reactions. In our initial work, we discovered that the dimerization of primary unsaturated alcohols to give α-hydroxymethyl ketones was promoted by RuHCl(CO)(PPh3)3. Some insights into the reaction mechanisms suggest that double bond-isomerization leading to aldehydes, transfer hydrogenation to give enals, formation of ruthenium enolates, aldol reactions of the enolates with aldehydes, and the subsequent β-hydride elimination are involved in the unusual dimerization. Taking advantages of the ability of transfer hydrogenation by RuHCl(CO)(PPh3)3, we developed reductive dimerization reaction of enals in the presence of secondary alcohols and cross-coupling reaction of enals with primary alcohols, both of which led to α-hydroxymethyl ketones. The regioselective addition of aldehydes to enones was also successful, which provides a useful entry to 2-alkyl-substituted 1,3-diketones. The ruthenium hydride-catalyzed cross-coupling reaction of dienes with aldehydes gave β,γ-unsaturated ketones in high yield with high regioselectivity. RuHCl(CO)(PPh3)3 is also an efficient catalyst for lactonization of both dialdehydes and keto aldehydes. The consecutive C-C and C-O bond forming reactions were achieved using enones and dialdehydes, which gave keto lactones in good yields.
N-Heterocyclic carbene (NHC) has been widely used as a ligand for transition metal complexes and as an organocatalyst. Herein, the recent progress of synthetic polymer chemistry made by NHC is briefly reviewed. NHC serves as an efficient catalyst for ring-opening polymerization of cyclic esters and group transfer polymerization of (meth)acrylates. Living polymerization of ethylene oxide proceeds by NHC initiator. New polymeric materials such as dynamic covalent polymers and main chain organometallic polymers can be prepared from difunctional NHC.