Catalytic oxidative 1,2-shift in 1,1'-disubstituted olefins using arene(iodo)sulfonic acid as the precatalyst and oxone as the oxidant.

An efficient, catalytic hypervalent iodine-mediated oxidative 1,2-shift of 1,1'-disubstituted olefins is described. This methodology provides concise access to homobenzylic ketones with electron-donating substituents. In the case of cyclic systems, this transformation results in ring-expanded ß-benzocycloalkanones, which are useful for further elaboration.

A general preparation of protected phosphoamino acids.

Fmoc-O-benzyl-l-phosphoserine is an important building block in the synthesis of Forigerimod, a phosphopeptide being investigated for Systemic Lupus Erythematosus (SLE). An efficient one-pot process was developed using inexpensive, readily available starting materials. This general procedure was used to prepare a variety of protected phosphoamino acids.

Asymmetric total synthesis of (-)-laulimalide: exploiting the asymmetric glycolate alkylation reaction.

A concise total synthesis of the potent antitumor macrolide (-)-laulimalide is described. The observation that homoallylic (or latent homoallylic) C-O bonds are present at C5, C9, C15, C19, and C23 led to the strategic decision to rely heavily on the asymmetric glycolate alkylation to construct both the C1-C14 fragment 3 and the C15-C27 subunit 4. A diastereoselective addition of a C1-C14 allylstannane to a C15-C27 alpha,beta-epoxyaldehyde served to join the two advanced fragments. A Mitsunobu macrolactonization of hydroxy acid 2 avoided isomerization of the sensitive 2,3-Z-enoate, which has been observed in base-catalyzed macrolactonizations. Removal of two TBS protecting groups to reveal the C15 and C20 hydroxyls occurred without rearrangement to isolaulimalide.

Asymmetric total synthesis of spongistatins 1 and 2.

The total synthesis of spongistatin 1 (1) and spongistatin 2 (2) has been achieved through an advanced-stage intermediate. The synthesis is highlighted by a highly convergent assembly of the four key fragments (the C1-C15 AB fragment 2, the C16-C28 CD fragment 3, the C29-C43 EF fragment 4, and the C44-C51 side chain 5) at a very advanced stage of the synthesis with minimal functional group interconversion. The CD fragment 3 functions as the central building block to which the other fragments are attached. The synthesis of the AB and CD spiroketal fragments is accomplished through the addition of a metalated gamma-pyrone to a beta-alkoxy aldehyde followed by spiroketalization. The EF subunit was assembled with high diastereoselectivity relying on asymmetric aldol reactions of chlorotitanium enolates of N-propionyl oxazolidinethiones and a double diastereoselective boron aldol to join the E and F fragments. Wittig coupling of the CD and EF fragments followed by a diastereoselective aldol reaction between the CDEF ketone and an AB aldehyde set the stage for attachment of the C44-C51 side chains and final macrolactonization and deprotection.