New applications of the mitsunobu reaction in the synthesis of C-2 N-methyl carbapenems

Synthesis and Stereochemical Assignments ofcis- andtrans-1-Amino- 4-ethylcyclohexa-2,5-diene as Models for Amiclenomycin

“…As nucleophiles, we first tried to use N-protected amines HN(Alloc) 2 [9] or HN(Ts)Alloc [10] under classical Mitsunobu conditions (DIAD, PPh 3 , CH 2 Cl 2 ), but the starting material was recovered unchanged. On the other hand, the alcohols 18 could be transformed into azides 19 with diphenylphosphoryl azide.…”

“…In addition, the trans geometry originally assigned to the natural product [1] on the basis of the value of the long-range coupling constant ( 5 J) between the two allylic hydrogen atoms of this single isomer was questionable, and it was Thus, another route had to be explored, in the form of a DielsϪAlder reaction between a 1,3-diene and an acetylene equivalent, since acetylene itself is not reactive enough. From the possible acetylene equivalents, we selected trans-1,2-bis(phenylsulfonyl)ethylene (9), developed by De Lucchi et al, [5] because of its high reactivity (the trans isomer is much more reactive than the cis one) and the mild conditions used to regenerate the double bond. Reductive elimination of the phenylsulfinyl groups can indeed be achieved at room temperature with sodium amalgam in methanol buffered with potassium dihydrogenophosphate.…”

Synthetic Strategies Employed for the Construction of Fostriecin and Related Natural Products

“…This set the stage for installation of the primary amine characteristic of the cyclohexane-containing members of the fostriecin family of natural products. This was achieved using a Mitsunobu reaction 111,112,230 giving the bis-Alloc protected amine 335 in 73% yield. Four steps were needed to deprotect the PMB ether, install the phosphate group using the phosphoramidite method of Bannwarth, 118 and globally deprotect the compound, yielding phoslactomycin B (7).…”

Total Synthesis of Phoslactomycin B and Its Biosynthetic Deamino Precursor

“…The remaining part of the synthesis involved integration of the amino and phosphate groups on the molecule. Introduction of the amino group was successfully carried out with HN(CO 2 -allyl) 2 under Mitsunobu conditions (DIAD, PPh 3 ) [25] to furnish 27 in 73 % yield. Selective protection of the primary and secondary alcohols with TESCl afforded 24 in 85 % yield.…”

“…The remaining tertiary hydroxy group at C8 in 24 was then protected to afford TMS ether 25, which was exposed to PPTS in THF/MeOH to yield 26 in 53 % yield, along with recovered 25 in 38 % yield (86 % yield of 26 based on recovered 25). Introduction of the amino group was successfully carried out with HN(CO 2 -allyl) 2 under Mitsunobu conditions (DIAD, PPh 3 ) [25] to furnish 27 in 73 % yield. To install the phosphate group, the PMB group was removed with DDQ, which proceeded cleanly; subsequent phosphorylation of the resulting alcohol 28 with (iPr) 2 NP(O-allyl) 2 [26, 12f] and 1H-tetrazole (then 35 % H 2 O 2 ) provided phosphate 29 in good yield.…”