Pedro M. Grima

2-Functionalized furans as precursors of versatile cycloheptane synthons

Abstract An study on the influence of steric and electronic effects of a function attached at C-2 of furans in the yield and diastereoselectivity of [4 + 3] cycloaddition reactions with oxyallyl cations is presented. In almost all studied furans a cis diastereospecificity and a high endo diastereoselectivity is observed. Increasing bulkyness of the function attached at C-2 of furans, the endo diastereoselectivity increases, but yield decreases. Increasing the electronic density of the furan system, by an electron donating group at C-2, both yield and diastereoselectivity increase.

New methodology for the [4+3] cycloaddition reactions: generation of oxyallyl cations from α,α′-diiodoketones under sonochemical or thermal conditions

A new methodology to perform [4+3] cycloaddition reactions of suitable dienes and 1,3-dimethyl-2-oxyallyl cations is presented. The reaction is carried out starting from commercially available dienes and easy-handling α,α′-diiodoketones, which are reduced by the Zn/Cu couple to generate the oxyallyl cation as intermediate. The reaction is carried out under mild thermal or sonochemical conditions at low temperatures (from 0 to −44°C) and for short reaction times (<15 min). This methodology represents a good alternative respect to the actual procedures based on other reducing agents or starting from more elaborate precursors of the oxyallyl cations.

Induction of asymmetry on the [4+3] cycloaddition reaction of C2-functionalized furans

A study of the induction of asymmetry on the [4+3] cycloaddition reaction of some 13 C2-substituted furan derivatives with 2-oxyallyl cation is presented. The asymmetry was induced by a chiral auxiliary on C2 of furan. A cis diastereospecificity and a high endo diastereoselectivity are observed in almost all studied cases. On decreasing the distance between the stereocenter of the chiral auxiliary and the reactive C2-carbon of the furan ring, the π-facial diastereoselectivity is increased, especially by using chiral furyl-sulfoxides.

New synthetic methodology to prepare polyfunctionalized heptane building blocks with four stereocenters: synthesis of the (±)-C17–C23 subunit of Ionomycin

A new synthetic methodology for preparing polyfunctionalized heptane building blocks with up to four stereocenters has been developed. 2,4-Dimethyl-1-methoxy-8-oxabicyclo-[3.2.1]-oct-6-en-3-one has been used as precursor, which can be easily prepared by a [4+3] cycloaddition reaction between 2-methoxy-furan and the oxyallyl cation generated in situ from 2,4-dibromo-3-pentanone. The cycloadducts have an acetal functionality on C1 which allows easy opening of the oxabicyclic system, affording versatile synthons. The application of this methodology to the synthesis of the C17–C23 subunit of Ionomycin is presented.

Synthesis of the C17–C23 subunit of Ionomycin from C1-functionalized 8-oxabicyclo[3.2.1]oct-6-en-3-one. New synthetic methodology to prepare polyfunctionalized heptane building blocks with four stereocenters

Abstract The application of a new methodology to synthesize the C17–C23 subunit of Ionomycin is presented. This synthetic methodology is based on the preparation of heptane building blocks with four stereocenters and up to four different organic functionalities. 2,4-Dimethyl-1-methoxy-8-oxabicyclo[3.2.1]oct-6-en-3-one has been used as a key intermediate, which can easily be prepared by a [4+3] cycloaddition reaction between 2-methoxy-furan and the oxyallyl cation generated in situ from 2,4-dibromo-3-pentanone. This cycloadduct has an acetal functionality on C1 which allows the easy opening of the oxabicyclic system, affording versatile synthons.

General method of assignment of relative stereochemistry in C‐1‐substituted 2,4‐dimethyl‐8‐oxabicyclo[3.2.1]oct‐6‐en‐3‐one by 1H and 13C NMR correlations

The 1H and 13C NMR spectra of cis‐endo (a) and cis‐exo (b) diastereoisomeric pairs of five differently C‐1‐functionalized 2,4‐dimethyl‐8‐oxabicyclo[3.2.1]oct‐6‐en‐3‐ones were completely assigned. Several trends regarding the variation of chemical shifts and coupling constants of hydrogen and carbon atoms, on changing the configuration at C‐2 and C‐4 in both diastereoisomers, were observed by correlation of spectral data: methyl groups attached at C‐2 and C‐4 in a appear in 1H NMR at higher field than in diastereoisomer b. Simultaneously, H‐2 and H‐4 result in a lower field in a than in b. Both effects are due to the different interactions of hydrogens H‐2, H‐4, H‐9 and H‐10 with the bridging oxygen. In 13C NMR spectra it is possible to observe an upfield shift of C‐9, C‐10 and C‐3 in b versus a. The difference observed in chemical shifts of the aforementioned hydrogens and carbons, between both diastereoisomers, allows one to assign the configuration at C‐2 and C‐4 in such structures. This phenomenon has wide scope and validity and could be applied to the stereochemical determination of any pair of diastereoisomers (a and b), independently of the function attached to C‐1 of the oxabicyclic system. ©1998 John Wiley & Sons, Ltd.

Asymmetry induction on the [4C(4π)+3C(2π)] cycloaddition reaction of C2-functionalized furans: influence of the chiral auxiliary nature

The study of the π-facial diastereoselectivity in the [4+3] cycloaddition reaction of thirteen different chiral 2-substituted furans with oxyallyl cations, under sonochemical and/or thermal conditions, is presented. In almost all studied furans, a cis diastereoselectivity and a high endo diastereoselectivity is observed. Decreasing the distance between the closest stereocenter of the chiral auxiliary and the reactive C2-carbon of the furan ring, increases the π-facial diastereoselectivity, especially by using chiral furyl-sulfoxides.

Generation of Oxyallyl Cations by Reduction of α,α′-Diiodoketones Under Sonochemical or Thermal Conditions: Improved Methodology for the [4C(4π;)+3C(2π;)] Cycloaddition Reactions

Abstract An improved methodology to carry out [4C(4π;)+3C(2π;)] cycloaddition reactions of dienes and oxyallyl cations, is presented. The reaction starts from commercially available dienes and easy-handling α,α′-diiodoketones, which are reduced by Zn (powder) or Zn/Cu couple to generate an oxyallyl cation as an intermediate. The reaction is carried out under mild thermal or sonochemical conditions at low temperatures (from 0 to −44°C) and for short reaction times (<15 min).

Complete assignment of 1H and 13C NMR data and establishment of the relative stereochemistry of C-1-functionalized 2,4-dimethyl-8-oxabicyclo[3.2.1] oct-6-en-3-one derivatives

The total assignment of the 1H and 13C NMR spectra of 24 cis‐endo and 15 cis‐exo diastereoisomers of C‐1‐substituted 2,4‐dimethyl‐8‐oxabicyclo[3.2.1]oct‐6‐en‐3‐one derivatives was deduced from the concerted application of DEPT, COSY, HETCOR, HMBC, HMQC and PS‐NOESY experiments. The relative stereochemistry of major (cis‐endo) and minor (cis‐exo) diastereoisomers was established on the basis of correlation studies of their 1H and 13C NMR data. Copyright