Heterocyclic olefins

The phosphine-phosphite BINAPHOS ligand was first used in the Rh-catalyzed asymmetric hydroformylation of heterocyclic olefins such as 2,5-dihydrofuran, 3-pyrroline derivatives, and 4,7-dihydro-1,3-dioxepin derivatives. It provided the optically active aldehydes as single products with enantioselectivity between 64-76% ee. In the hydroformylation of 2,5-di-... 

S — T absorption spectra are obtained for aromatics, heterocyclics, olefines and acetylenes. The transition disappears on removal of oxygen. It is suggested that a charge-transfer complex (A+ OJ) (Section 3.10.1) is formed which relaxes the spin multiplicity restrictions. 

The phenylselenenyl chloride induced intramolecular ring closure of ro-aminoalkenes can be utilized in the synthesis of nitrogen heterocycles. Olefinic primary amines do not cyclize readily in this reaction, while urethane derivatives and secondary amines cyclize according to the following scheme55 56. 

Heterocyclic dienes and heterocyclic olefins in [4 + 2]- and [2 + 21-cycloaddition reactions 88T6755. 

Certain aromatic and heterocyclic olefinic esters ate best prepared by condensation of ethyl acetate and aromatic aldehydes by sodium sand (Claisen). Benzaldehyde in this reaction gives ethyl cinnamate, C,HsCH=CHC03C,H5 (74%). p-Methylbenzaldehyde, furfural, furylactolein, and 2-thiophenecarboxaldehyde have been condensed in a similar manner. 

The heterocyclic olefins, thiophene and selenophene, also form 7T complexes upon reaction with (pyridine) ,Cr(CO)3 in the presence of a Lewis acid (PFj) (447). On the ba.sis of spectral data, structure (41) has been assigned to the products. 

Brown, H. C., Prasad, J. V. N. V. Hydroboration of heterocyclic olefins - a versatile route for the synthesis of both racemic and optically... 

Hu et al. [104] disclosed that the spiro phosphine oxide ligand (/ )-30a is highly efficient for the Pd-catalyzed Heck reaction of cyclic and heterocyclic olefins with aryl triflates. An asymmetric domino Heck cyclization was established using catalyst Pd/(/ )-30a to form fused carbo- and heterocycles with excellent stereoselectivity (Scheme 42) [105]. This method was used in a short synthesis of (-)-martinellic acid, a primary ingredient in traditional eye medicine in South America. 

Some heterocyclic systems such as tetrahydrofuxan, tetrahydropyran, thiophene, and pyrrolidine are foimd in a wide range of biologically active compounds. Hydroformylation of these heterocyclic olefins provides a potential synthetic route for the synthesis of these targets (Scheme 11) [93,94]. Asymmetric hydroformylation of a-methylene-y-butyrolactone using the cationic Rh(I)-(l )-BINAP complex as a catalyst is also reported to give an aldehydic lactone containing a quaternary chiral center in up to 37% ee [95]. 

Heterocyclization. Olefinic w-ethoxylactams are cyclized by formic acid (20°) the actual intermediate is probably a cyclic acylimmonium species. Examples ... 

The hydroboration of heterocyclic olefins having oxygen [50-56], sulfur [57], and nitrogen [58-68] are reported. Brown and coworkers [69] have conducted detailed hydroboration studies of many heterocyclics with an endocyclic double bond with borane-methylsulfide BMS, 9-BBN, CtuqBH, and SiajBH and have established the optimum conditions for clean and quantitative hydroboration. The hydroboration of 2,3- and 2,5-dihydrofuran with BMS (3 1 molar ratio) at 25 °C for 1 h afibrds trialkylborane, readily oxidized to 3-hydroxytetrahydro-furan, in excellent yield. But the synthesis of dialkylboranes from these olefins using olefins, BMS in 2 1 ratio is not possible at 0 °C. However, hydroboration of 2,3-dihydrofuran proceeds cleanly with 9-BBN in 1 1 ratio and oxidation affords the desired 3-hydroxytetrahydrofuran, in excellent yield. Similar results are obtained with dicyclohexylborane and disiamylborane (Table 5.14). 

The relative rates of hydroboration of representative heterocyclic olefins with 9-BBN have been studied [72] at temperature 25 °C, as most of the large amount of data for relative reactivities with 9-BBN is available at this temperature. These rates of reaction for heterocyclic olefins are compared with SiajBH as the hydroborating agent at 0 °C, which is described by Zweifel and Plamon-don [50]. 

Brown et a/ [1] have elegantly hydroborated a variety of heterocyclic olefins, which on oxidation yield the corresponding alcohols in excellent yields. In the case of heterocyclic olefin containing a double bond a to the heteroatom, the hydroboration reaction is highly regioselective, placing boron at the (3-carbon atom. The use of 9-BBN for the synthesis of variety of heterocyclic alcohols is given in Chart 6.21. 

The group of Czekelius reported the NHC-gold(I) complex 117 bearing a highly sterically hindered ligand with a tetrahydroisoquinoline backbone (Scheme 3.75) [105]. The catalytic application of this complex was studied in the desymmetrization of diynesulfonamide. The heterocyclic olefin was obtained in good yield (77%) and moderate enantioselectivity (51% ee). 

Certain hydroboration reactions which are slow under normal conditions due to their heterogeneous nature proceed much faster under the effects of ultrasound. Several acyclic and cyclic trienes have been hydroborated with borane or triethylamineborane in THF and the stereochemistry of the products investigated. A systematic study of the hydroboration of representative heterocyclic olefins with four different reagents has been undertaken in order to establish optimum conditions for the reactions. This study has been followed by an investigation into the relative rates of reaction of 9-BBN with oxygen and sulphur containing heterocyclic olefins. ... 

The first Z to E isomerization of a heterocyclic olefin (thiacyclo-oct-4-ene) has been reported. ... 

Horiuchi T, Ohta T, Shirakawa E, Nozaki K, Takaya H. Asymmetric hydroformylation of heterocyclic olefins catalyzed by chiral phosphine-phosphite-Rh(I) complexes. /. Org. Chem. 1997 62 4285 292. 

This chemistry has also been used to synthesise saturated heterocycles, which are key building blocks in drug molecules, by reduction of heterocyclic olefins where the heteroatom is remote from the olefin. This was applied to the synthesis of preclamol, a D-2-like dopamine autoreceptor agonist, where 22 was reduced to give 24 in excellent yield and enantios-electivity at 1 mol% catalyst loading (Scheme 14.8). ... 

Asymmetric hydroformylation of heterocyclic olefins provides potentially useful synthetic building blocks for the syntheses of biologically active compounds. The reactions of 2,5-dihy-drofuran 27a (Eq. 7), dihydropyrroles (27b, 27c, and 29) (Eqs. 7.7,7.8), and dioxepin 32 (Eq. 7.9) give the corresponding aldehydes with 47-88% ee [92]. Reaction of a-methylene-y-buty-rolactone (34) using cationic Rh-(R)-BINAP complex as the catalyst affords the formyUactone 35, bearing a quaternary chiral center, with <37% ee (Eq. 7.10) [93]. 

---