Fe/Cu-Mediated One-Pot Ketone Synthesis

An Fe/Cu-mediated one-pot ketone synthesis was reported. Unlike Ni- and Pd-mediated one-pot ketone syntheses, the reported Fe/Cu-mediated method allowed selective activation and coupling of alkyl iodides over vinyl iodides. The newly developed one-pot ketone synthesis was applied to a synthesis of vinyl iodide/ketone <b>13</b>, the left half of halichondrin B, as well as vinyl iodide/ketone <b>8a</b>, the C20–C26 building block of halichondrins

Stereocontrolled Synthesis of Left Halves of Halichondrins

A stereocontrolled synthesis of the left halves of halichondrins was reported. An intramolecular oxy-Michael reaction <i>under basic conditions</i> was used to construct the [6,6]-spiroketal in a stereocontrolled manner. With this approach, the left halves of halichondrins, homohalichondrins, and norhalichondrins were synthesized

Stereocontrolled Synthesis of Left Halves of Halichondrins

A stereocontrolled synthesis of the left halves of halichondrins was reported. An intramolecular oxy-Michael reaction <i>under basic conditions</i> was used to construct the [6,6]-spiroketal in a stereocontrolled manner. With this approach, the left halves of halichondrins, homohalichondrins, and norhalichondrins were synthesized

A Concise and Unified Strategy for Synthesis of the C1–C18 Macrolactone Fragments of FD-891, FD-892 and Their Analogues: Formal Total Synthesis of FD-891

A concise and unified strategy for the synthesis of C1–C18 macrolactone fragments of FD-891 and FD-892 as well as their analogues is reported. The strategy includes a stereoselective vinylogous Mukaiyama aldol reaction (VMAR) using chiral silyl ketene <i>N,O</i>-acetal to construct C6–C7 stereocenters, an <i>E</i>-selective ring closing metathesis to construct a C12–C13 olefin, and stereodivergent construction of a C8–C9 epoxide

Unified Synthesis of Right Halves of Halichondrins A–C

The right halves of halichondrins A–C were synthesized by coupling the common C20–C37 building block <b>9</b> with the C1–C19 building blocks <b>10a</b>–<b>c</b>, respectively. Catalytic, asymmetric Ni/Cr-mediated coupling was used for three C–C bond formations. For all cases, the stereochemistry was controlled with the Cr catalyst prepared from the chiral sulfonamide identified via the toolbox approach. For (<b>3 + 4</b>)-, (<b>6 + 7</b>)-, and (<b>9 + 10</b>)-couplings, the stereoselectivity of 28:1, >40:1, and ∼20:1 was achieved by the Cr catalysts prepared from (<i>S</i>)-<b>H</b>, (<i>S</i>)-<b>I</b>, and (<i>R</i>)-<b>L</b>, respectively. Unlike the first and second couplings, the third coupling used the structurally complex nucleophile. It was demonstrated that the coupling efficiency was excellent even with the electrophile/nucleophile molar ratio = 1.0/1.1. In addition, the third coupling was achieved with the substrate bearing a free hydroxyl group. The products obtained in the Ni/Cr-mediated couplings were converted to the right halves of halichondrins A–C in excellent overall yields. The right halves of halichondrins A–C (<b>1a</b>–<b>c</b>) were synthesized in 28, 24, and 24 steps from commercial d-galactal in 13.4%, 21.1%, and 16.7% overall yield, respectively