Extending distannoxane double ladders using rigid spacers: a double ladder with eight chiral tin atoms-and a twist!

The new bulky silicon-containing ditin precursor p-(RCl₂SnCH₂SiMe₂)₂C₆H₄ (R = CH₂SiMe₃ (4)) has been synthesized and further reacted to form a unique double ladder {[p-(R(Cl)SnCH₂SiMe₂)₂C₆H₄]O}₄ (6). The two layers within 6 are twisted with respect to one another, resulting in a helical motif and a total absence of molecular symmetry so that there are eight chiral tin atoms within the system. The structure is compared to the double ladder {[m-(R(Cl)SnCH₂CH₂)₂C₆H₄]O}₄ (11), which was prepared from the less sterically demanding ditin precursor m-(RCl₂SnCH₂CH₂)₂C₆H₄ (10). The two layers within 11 are parallel, and the molecule contains only two kinds of tin atom.

Chiral trialkoxysilanols derived from terpene alcohols. Molecular structures of tris([(1S)-endo]-(-)-bornoxy)silanol and tetrakis((-)-menthoxy)silane

Terpene alcohols (−)-menthol and [(1S)-endo]-(−)-borneol react with SiCl₄ in the presence of base to give (MenO)₃SiCl (1) and (BorO)₃SiCl (2) in high yields. Hydrolysis of 1 yields (MenO)₃SiOH (4) and (MenO)₄Si (3). Hydrolysis of 2 yields only (BorO)₃SiOH (5). The crystal structures of 3 and 5 are reported.

Single enatiomer free-radical chemistry - Lewis acid-mediated reductions of racemic halides using chiral non-racemic stannanes

Additions of one to two equivalents of Lewis acids that include magnesium salts to free-radical reduction reactions involving ester functionalized radicals and (1R,2S,5R)-menthyldiphenyltin hydride 4, bis((1R,2S,5R)-menthyl)phenyltin hydride 5, tris((1R,2S,5R)-menthyl)tin hydride 6, bis((1R,2S,5R)-menthyl)-[8-(N,N-dimethylamino)naphthyl]tin hydride 12, bis((1R,2S,5R)-menthyl)-[1-((S)-N,N-dimethylaminoethyl)phenyl]tin hydride 13 or 3α-dimethylstannyl-5α-cholestane 14 result in remarkable enantioselectivities. Examples include (S)-naproxen ethyl ester 16, produced in 74% yield and greater than 99% ee at −78°C from the bromide and 5 in the presence of MgBr₂, and ethyl (R)-N-trifluoroacetyl-_D-phenylglycinate 18, obtained in 78% yield and 99% ee under identical conditions. Kinetic and computational studies provide insight into the origins of these observations.

Strategies and methods for the attachment of amino acids and peptides to chiral [n]polynorbornane templates

A versatile synthesis of amino acid and peptide functionalised [n]polynorbornane scaffolds is described. The frameworks are constructed using the stereoselective and regioselective cycloaddition of suitably functionalised chiral cyclobutene epoxides with similar norbornenes. The strategies employed allow a range of topologies to be accessed and a number of regioselectively addressable linkage points to be accommodated.

Chiral organochlorosilanes derived from terpenes: diastereoselective hydrosilylation of methylene bicyclo[2.2.1]heptanes with HSiMenCln-2 (n=0-2)

The H₂PtCl₆ catalysed hydrosilylation of the terpenes (+)-α-fenchene (XI), (−)-2-methylene bornane (XII), (+)-camphene (XIII) and (−)-3-methylene fenchane (XIV) using HSiMe₂Cl or HSiMeCl₂ proceeds with high regioselectively and in some cases, with high diastereoselectivity. KF-assisted oxidation of the hydrosilylation products gives predominately endo-terpene alcohols. The alcohols have inverted endo/exo ratios to those formed by oxidative hydroboration. Reaction of XIV with HSiMe₂Cl or HSiMeCl₂ is accompanied by a clean rearrangement of the isocamphane skeleton into (+)-2-methylene bornane (XII) prior to hydrosilylation.

The hydrosilylation of α-fenchene, 2-methylene bornane, camphene and 3-methylene fenchane with chlorosilanes HSiMe_nCl_n − 2 (n=0–2) occurred with varying degrees of diastereoselectivity providing anti-Markovnikov product mixtures, in which the endo-isomers dominate over the exo-isomers. These mixtures were oxidized to give the corresponding terpene alcohols. 3-Methylene fenchane undergoes a rearrangement into 2-methylene bornane prior to hydrosilylation.

Chiral organotin hydrides as enantioselective reducing agents

This thesis reports on the feasibility of the utilization of organotin hydrides as enaantioselective free radical reducing agents. The chiral organotin hydrides prepared contain the bulky chiral (1R,2S,5R)-menthyl substituent and in some cases also contain a stereogenic tin centre. Reaction of (1R,2S,5R)-menthylmagnesium chloride (MenMgC1) with triphenyltin chloride in THF proceeds with epimerization of the C-1 carbon of the menthyl group and results in a mixture of (1R,2S,5R)-menthyltriphenyltin and (1S,2S.5R)-menthyltriphenyltin. Addition of Lewis bases such as triphenylphosphine to the THF solution of triphenyltin chloride prior to the addition of the Grignard reagent suppresses epimerization and enables isolation of pure (1R,2S,5R)-menthyltriphenyltin. (1R,2S,5R)-Menthyltriphenyltin is the precursor for the synthesis of (1R,2S,5R)-menthyldiphenyltin hydride as well as (1R,2S,5R)-menthyl-containing organotin halide derivatives. A crystal structure of (1R,2S,5R)-menthylphenyltin dibromide and (1R,2S,5R)-menthylphenyltin dichloride confirmed the configuration of the menthyl substituent in these compounds. Reaction of MenMgC1 with diphenyltin dichloride in THF proceeds with no epimerization of the C-1 carbon of the menthyl group and bis((1R,2S,5R)-menthyl)diphenyltin is formed. A crystal structure of (1R,2S,5R)-menthyltriphenyltin confirmed the configuration of the menthyl substituent. Bis((1R,2S,5R)-menthyl)diphenyltin is used to form bis((1R,2S,5R)-menthyl)phenyltin hydride as well as other bis(1R,2S,5R)-menthyl derivatives. A series of chiral non-racemic triorganotin halides and triorganotin hydrides containing one or two (1R,2S,5R)-menthyl substituents as well as various potentially intramolecular coordination substituents were synthesized and characterized. The intramolecular substituents include the 8-(dimethylamino)naphthyl, 2-[(1S)-1-dimethylaminoethyl]phenyl, 2-(4,4-dimethyl-2-oxazoline)-5-methylphenyl and the 2-(4-(S)isopropyl-2-oxazoline)-5-methylphenyl substituents. Each compound containing a stereogenic tin centre was synthesized as diastereomeric mixtures. AM1 calculations of these compounds provide good qualitative predictability of the molecular geometries observed in the solid state as well as the diastereomeric ratios observed in solution. X-ray analysis of some of the organotin halides containing intramolecular coordination substituents revealed a tendency towards penta-coordination at the tin centre as a result of N-Sn interactions. The chiral organotin hydrides synthesized were found to be poor enantioselective free radical reducing agents. However, the addition of one molar equivalent of achiral or chiral Lewis acids to the free radical reduction reactions involving these organotin hydrides results in remarkable increases in enantioselectivity. There are numerous examples in which enantioselectivities exceed 80% and three examples of enantioselectivites which are equal and above 90% with one outstanding enantioselective outcome of ≥99%. These results appear to be the highest enantioselectivites for organotin hydride radical reductions reported to date. There is strong evidence to suggest that the chiral menthyl group of the organotin hydride directs the stereochemical outcome in the reduced product. The results also suggest that an increase in the number of menthyl substituents attached to tin or the introduction of intramolecular coordination substituents does not necessarily results in a greater increase in enantioselectivity. Preliminary studies into the synthesis of organotin hydrides containing Lewis acid functionalities are also reported. A zirconium chloride functionality was found to be incompatible with organotin hydride. However, an organotin hydride containing a trialkylboron Lewis acid functionality attached via an alkyl chain was successfully synthesized. Although this reagent was only stable in the preparative THF solution, it was still found to be effective at reducing benzaldehyde to benzyl alcohol.

Chiral and achiral precursers for extended and supramolecular compounds

Organometallic compounds are building blocks for materials with applications in catalysis, pharmaceutical production and molecular sensors. Research presented in this thesis focused on the design and synthesis of compounds with supramolecular architectures. Crystal engineering these new compounds provides the basis for the next generation of advanced materials required by industry.

Investigation into the application of chiral organotin hydrides as enantioselective free radical reducing agents

Investigates the viability of selectively preparing molecules demonstrating the property of left or right "handedness" via free radical reactions. Experimental investigations suggested that a subtle interaction exists between the substituents of an organotin hydride and a target carbon radical during hydrogen atom transfer reactions.

Novel routes to new chiral rings and cages

The successful synthesis and characterisation of a series of new chiral cages was achieved through the use of a BINOL backbone linked to a variety of organotin carboxylates. These novel chiral cages may ultimately find use as catalysts in reaction syntheses for the pharmaceutical industry.