Multigramme synthesis and asymmetric dihydroxylation of a 4-fluorobut-2E-enoate.

Esters of crotonic acid were brominated on a multigramme scale using a free radical procedure. A phase transfer catalysed fluorination transformed these species to the 4-fluorobut-2E-enoates reproducibly and at scale (48-53%, ca. 300 mmol).

Why is RCM favoured over dimerisation? Predicting and estimating thermodynamic effective molarities by solution experiments and electronic structure calculations.

The thermodynamic effective molarities of a series of simple cycloalkenes, synthesised from α,ω-dienes by reaction with Grubbs' second generation precatalyst, have been evaluated. Effective molarities were measured from a series of small scale metathesis reactions and agreed well with empirical predictions derived from the number of rotors and the product ring strain. The use of electronic structure calculations (at the M06-L/6-311G** level of theory) was explored for predicting thermodynamic effective molarities in ring-closing metathesis.

On the relationship between structure and reaction rate in olefin ring-closing metathesis.

In the RCM reactions of a series of simple α,ω-dienes, the relative order of reactivity has been unambiguously determined showing that cyclohexene forms faster than cyclopentene or cycloheptene. 1,5-Hexadiene inhibits the RCM of 1,7-octadiene; 1,5-hexadiene cannot progress to the RCM product (cyclobutene) but forms an unexpectedly stable cyclic η(2)-complex.

Syntheses of difluorinated carbasugar phosphates from trifluoroethanol.

Difluorinated cyclohexene diols (prepared from trifluoroethanol) can be elaborated to racemic analogues of phosphorylated sugars via regioselective protection and phosphorylation of the exposed C-1 hydroxyl group. Cis-diol protection was achieved using stannylene methodology, though the regioselectivity depended on the orientation of the methyl group at C-5. UpJohn dihydroxylation is effective with the phosphotriester in place and global deprotection to the tetrol monophosphates is efficient.

An appraisal of oxoketene cycloaddition methodology for the synthesis of 2,6-dideoxysugars and fluorinated 2,6-dideoxysugars.

The cycloaddition reaction of acylketenes with vinyl ethers affords an extremely direct route to 2,6-dideoxysugars and their methyl ethers. The lithium enolate of commercial 2,6,6-trimethyldioxinone 3 was fluorinated in good yield to afford fluorinated dioxinone 8. An illustrative range of fluorinated 2,6-dideoxysugar derivatives was prepared via the acetyl ketene-vinyl ether cycloadduct.

Developing an asymmetric, stereodivergent route to selected 6-deoxy-6-fluoro-hexoses.

Free radical bromination and nucleophilic fluorination allows the conversion of methyl sorbate into the 6-fluoro analogue which undergoes sequential asymmetric dihydroxylation reactions. A range of 6-deoxy-6-fluorosugars were prepared by using different combinations of ligands. While the enantiomeric excesses obtained were comparable to those from other 6-substituted sorbates, the regioselectivity of dihydroxylation was moderate, with both 2,3- and 4,5-diols being obtained.