New routes to 2,5-disubstituted tetrahydropyrans and P-stereogenic heterocycles via ring-closing metathesis

• Main Author: Wu, Xiao
• Other Authors: O'Brien, Peter
• Published: University of York 2013
• Subjects: 547
• Online Access: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.581669

New methodologies have been developed for the synthesis of 2,5-disubstituted tetrahydropyrans and for the asymmetric synthesis of P-stereogenic phospholene boranes. Synthesis of 2,5-disubstituted tetrahydropyrans in a racemic fashion was achieved via Grignard addition, O-alkylation, ring-closing metathesis and hydrogenation. Using this route, seven potential perfumery compounds were produced in good overall yield. Olfactory evaluation of the potential perfumery molecules accessed the majority of products as having a predominant characteristic of citrus note and others having a floral note. In addition, asymmetric synthesis of two saturated cyclic ethers was achieved using an asymmetric deprotonation approach. An alternative route to an enantioenriched alcohol using catalytic asymmetric deprotonation and trapping with Andersen’s sulfinate was briefly studied and proved successful. The asymmetric synthesis of P-stereogenic phospholene boranes was investigated. First, three chiral diamines were synthesised and their asymmetric induction was tested in the asymmetric lithiation of t-butyl phosphine boranes. Subsequently, the asymmetric synthesis of P-stereogenic vinylic phospholene boranes was carried out. Using s-BuLi/(_)-sparteine as a base, alkylated phosphine boranes were isolated with good yield and high enantioselectivity. A telescoped regioselective deprotonation/trapping of paraformaldehyde and elimination reaction was developed to gain access to the dienes. Finally, ring-closing metathesis afforded the desired vinylic phospholene boranes. The application represents the first example of asymmetric synthesis of P-stereogenic vinylic phospholene boranes.