Michael S. Sherburn

Practical Synthesis of the Dendralene Family Reveals Alternation in Behavior

Back from obscurity: The practical synthesis of the first six members of the fundamental class of acyclic branched oligoalkenes has been achieved. The syntheses allow access to the target compounds on multigram scales in good yields. Members of the family with even numbers of double bonds are significantly more stable than those with odd numbers (see picture), and exhibit different chemical reactivities in Diels-Alder reactions.

Practical Synthesis and Reactivity of [3]Dendralene

A convenient and high-yielding three-step synthesis of the simplest branched triene, [3]dendralene, has been devised. The synthesis is robust and operationally simple, requiring no chromatography and involving no protecting groups or specialized equipment, allowing the synthesis of the volatile hydrocarbon in pure, solvent free form on a multigram scale. The stability, dimerization when stored neat, and Diels-Alder reactivity of [3]dendralene--including double cycloaddition sequences and catalytic enantioselective variant--are reported.

Total Synthesis of Incarviditone and Incarvilleatone

The total synthesis of the racemic natural products (±)-incarviditone and (±)-incarvilleatone has been accomplished in three steps via biomimetic dimerization of (±)-rengyolone. Homochiral dimerization of (±)-rengyolone affords (±)-incarviditone through a domino oxa-Michael/Michael sequence. Heterochiral dimerization, involving a domino oxa-Michael/Michael/aldol reaction sequence, affords (±)-incarvilleatone. Single-crystal X-ray analysis of a derivative of (±)-incarviditone has resulted in revision of the originally proposed structure.

Pseudopterosin synthesis from a chiral cross-conjugated hydrocarbon through a series of cycloadditions

The pseudopterosins are a family of diterpene marine natural products, which, by virtue of their interesting anti-inflammatory and analgesic properties, have attracted the attentions of many synthetic chemists. The most efficient syntheses reported to date are 14 and 20 steps in the longest linear sequence for chiral pool and enantioselective approaches, respectively, and all start with precursors that are easily mapped onto the natural product structure. Here, we describe an unconventional approach in which a chiral cross-conjugated hydrocarbon is used as the starting material for a series of three cycloadditions. Our approach has led to a significant reduction in the step count required to access these interesting natural products (10 steps chiral pool and 11 steps enantioselective). Furthermore it demonstrates that cross-conjugated hydrocarbons, erroneously considered by many to be too unstable and difficult to handle, are viable precursors for natural product synthesis.

Formal total synthesis of triptolide

A new approach to the medicinally-important natural product triptolide is significantly shorter than previous syntheses, highly convergent and avoids the use of protecting groups; key features include two Diels-Alder reactions and a new deoxygenative aromatisation process.

Multi-Bond Forming Processes in Efficient Synthesis

An increasing number of synthetic organic chemists are embracing the philosophy of efficiency. Herein we highlight multi-bond forming processes, which form two or more new covalent bonds in a single synthetic operation. Such processes, which have the ability to rapidly increase structural complexity, are preeminent in contemporary synthetic organic chemistry. In this short review we classify, analyse, and contrast contemporary multi-bond forming processes, frame these cutting edge contributions within a historical context, and speculate on likely future developments in the area.

Total Synthesis and Structural Revision of the Alkaloid Incargranine B

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Synthesis and properties of the ivyanes: the parent 1,1-oligocyclopropanes

Practical syntheses of the first six members of the ivyane (1,1-oligocyclopropane) family of fundamental hydrocarbons have been achieved from the cross-conjugated polyenes known as dendralenes. Evidence for helical conformations in both the solid state and in solution is presented. [6]Ivyane exhibits one of the highest experimental heats of combustion recorded for a hydrocarbon. Ring-opening reactions of ivyanes furnish new and interesting structures that are difficult to access by conventional means.

Nitroso-dienophile additions to dendralenes: a short synthesis of branched aminosugars.

The first heteroatom-based dienophile cycloadditions to cross-conjugated alkenes ([n]dendralenes) are reported. Nitroso-dienophiles undergo smooth single and double Diels-Alder additions to the parent dendralenes with orientational regio- and stereoselectivity and, notably, with reactivity that depends upon the parity of the [n]dendralene. The first crystal structure of a cross-conjugated hexaene is reported. Vasellas nitroso-sugar reagent gives a highly enantiomerically enriched double cycloadduct with [3]dendralene. This bicyclic oxazine is successively dihydroxylated and then ring-opened to form a branched chain diamino tetrol.

Synthesis and applications of tricarbonyliron complexes of dendralenes.

[3]Dendralene and [4]dendralene are converted smoothly into tricarbonyliron complexes. The structures of four complexes analyzed by DFT and single-crystal X-ray analysis show that, in contrast to free hydrocarbons, complexed dendralenes prefer a roughly in-plane conformation. The complexes are stable towards Fe(CO)(3) group migration up to 150 °C. The synthetic value of Fe(CO)(3) complexation in the dendralene series is demonstrated through a variety of selective synthetic manipulations (Diels-Alder reaction, dipolar cycloaddition, Simmons-Smith cyclopropanation, dihydroxylation, olefin cross metathesis) that are not achievable by direct transformation of the free hydrocarbons. Application to the synthesis of a previously unreported, highly reactive linear/cross-conjugated hydrocarbon is also described.