Synthesis of Enantiopure Termini-Differentiated Heptane Stereotriads.¹ Application to Side Chain-Functionalized Tetrahydrofurans of IKD-8344

Abstract

Enantiopure epoxy cycloheptenyl sulfones syn-7b and anti-7b are prepared in five high-yielding and stereospecific operations from 1, 3-cycloheptadiene. These substrates serve as effective precursors for cis- and trans-substituted tetrahydrofurans (12, 10) which are segments of the antineoplastic agent IKD-8344.

Copper‐Catalysed Addition of Organometallic Reagents to Vinyl Diepoxides − A Novel Route to Oxa‐Bridged Systems and to Substituted Allylic Alcohols

“…Recently, the regioselective intramolecular alkylation observed in cycloheptadienyl epoxyvinyl sulfones was explained in terms of a bidentate coordination of the acid catalyst with both the epoxide and the sulfonyl oxygen atoms. [19] Our results indicate that there is an intrinsic preference, albeit modest, for a bicyclic 6/5 ring system over the other (path b vs. path a, Figure 4), without the intervention of any chelated activating functionality.…”

Improved and Environmentally Friendly Large-Scale Preparation of Cyclohexadienyl-, Cycloheptadienyl Sulfone and Enantiopure Epoxy Cycloheptyl Sulfones

“…It was found that the catalyst can be lowered to 1 mol% without significant loss of yield or ee, but the reaction time was overly long. This problem was overcome by using 100 mol% of NH 4 OAc; other possible co-catalysts were screened at various temperatures but none were as efficient as NH 4 OAc. This modification combined with the 1 mol% catalyst loading, made it possible to run the reaction in a reasonable time period with excellent results, but active catalyst can no longer be recovered (Table 2).…”

“…The solid product was washed with water (2 L) and dried by forcing air through the filter cake for 24 h to give a pure and pale yellow solid (2, 1.1 kg, 51% yield over 5 steps from cyclohexanone, 98% purity by HPLC); mp 58-60 °C (lit. 2 4 OAc is dissolved before proceeding further. The Jacobsen Mn catalyst (8.3 g, 0.01 mol) was then added and the solution immediately turned brown (due to the catalyst).…”

“…Additionally, one could obtain either epoxide enantiomer by application of the appropriate commercially available enantiomeric catalyst. 3,4 A major drawback of the JAE was scalability of the reaction. The development of an optimized process for the preparation of diene 1, 2 and epoxide 3 is now at hand.…”

A Facile Method for Synthesis of 5‐Hydroxypentene via Sonochemical Barbier Reaction

“…5-Hydroxypentenes have received much attention as synthetic intermediates for synthesis of biologically active tetrahydrofuran derivatives. [1][2][3][4][5][6][7][8][9][10][11] 5-Hydroxypentenes have been prepared by the reactions of allylic organometallics of indium, 12 magnesium, 13 and tin, 13 with epoxide or cyclopropylmethylmagnesium bromide 14 with aldehyde. A mixture of regioisomeric alcohols was generally produced.…”