Dale E. Ward

A simple method for the microscale preparation of mosher's acid chloride

Abstract Moshers acid is treated with oxalyl chloride in the presence of DMF in hexane. Filtration and concentration provide the acid chloride which is suitable for use without further purification. The procedure is amenable to microscale.

Chemoselective Reductions with Sodium Borohydride. Aldehydes vs. Ketones

Abstract Aldehydes can be reduced in the presence of ketones by sodium borohydride in 30% ethanol in dichloromethane at -78° C. The selectivity is generally greater than 95%.

A general method for the selective reduction of ketones in the presence of enones.

Abstract Ketones can be reduced in the presence of conjugated enones by sodiumborohydride in 50% methanol in dichloromethane at −78°C. The selectivity is generally excellent. In favorable cases the reaction can be carried out at room temperature in dichloromethane with acetic acid as catalyst.

Synthesis of the host-selective phytotoxin destruxin B. Avoiding diketopiperazine formation from an N-methyl amino acid dipeptide by use of the Boc-hydrazide derivative

An efficient synthesis of the cyclic hexdepsipeptide destruxin B from its component residues is described that involves a [3+3] fragment coupling followed by cyclization via the azide method. A novel feature of the synthesis is the use of the Boc-hydrazide protecting group for the C-terminal N-methylalanine residue. This group serves both to inhibit facile diketopiperazine formation from the N-methylvalyl-N-methylalanine dipeptide and as a latent activating group for hexadepsipeptide cyclization.

Enantiospecific Total Synthesis of Lairdinol A

The synthesis of lairdinol A, a component of the host-selective phytotoxin depsilairdin, was achieved in 12 steps (18% overall yield) without the use of protecting groups starting with the Diels-Alder reaction of (R)-carvone with 3-trimethylsilyloxy-1,3-pentadiene. The key step established the trans ring fusion by preferential epoxidation of a trans-fused enone in an equilibrating mixture of the cis-fused and trans-fused diastereomers (i.e., equivalent to a dynamic kinetic resolution of these isomers). The synthesis confirms the absolute configurations of lairdinol A and its enantiomer, cyperusol C.

Syn-anti isomerization of aldols by enolization.

[reaction--see text] A variety of aldol adducts (i.e., 3-hydroxy ketones) are shown to undergo syn-anti isomerization in the presence of imidazole by an enolization mechanism with negligible retroaldol or elimination products.

THE THIOPYRAN ROUTE TO POLYPROPIONATES REVISITED: SELECTIVE SYN AND ANTI ALDOL REACTIONS VIA 3,6-DIHYDRO-4-TRIMETHYLSILYLOXY-2H-THIOPYRAN

Aldol reaction of the amine free Li enolate of tetrahydro-4H-thiopyran-4-one with 1,4-dioxa-8-thiaspiro[4.5]decane-6-carboxaldehyde gives mainly the 2,3-anti-3,4-syn aldol (7:1) in good yield; reaction of the LDA generated lithium enolate proceeds poorly. Using the trimethylsilyl enol ether and TiCl4 gives the 2,3-syn-3,4-syn aldol (> 10:1). The adducts can be used for polypropionate synthesis.

[3+3] Annulation by sequential two electron and one electron allylation

Abstract 3-phenylthio-2-(trimethylsilymethyl)propene is a convenient conjunctive reagent for the preparation of methylenecyclohexanes via a [3+3] annulation. The trimethylsilyl group facilitates the Lewis acid catalyzed allylation of an aldehyde or acetal while the phenylthio group directs a 6-endo-trig radical cyclization reaction.

On the Origin of Siphonariid Polypropionates: Total Synthesis of Caloundrin B and Its Isomerization to Siphonarin B

Enantioselective synthesis of the enantiomer of caloundrin B was achieved by strategic aldol coupling of an enantiopure trioxaadamantane-containing ketone with a racemic pyrone-containing aldehyde via kinetic resolution. In the presence of imidazole, ent-caloundrin B is cleanly isomerized to ent-siphonarin B confirming the proposed structure and absolute configuration for caloundrin B and establishing that it is a plausible biosynthetic product from which siphonarin B and baconipyrones A and C can originate.

Synthetic Studies on Siphonariid Polypropionates: Synthesis and Isomerization of the Caloundrin B Trioxaadamantane Ring System

(1R,3R,5R,7R,8S,9R,10S)-3,5-Diethyl-8,9,10-trimethyl-2,4,6-trioxatricyclo[3.3.1.1(3,7)]decan-1-ol (II), a model of the trioxaadamantane ring system embedded in caloundrin B, was prepared by isomerization of the thermodynamically unstable (9S)-diastereomer (I) in the presence of imidazole. Alternatively, isomerization of I with HF.py or DBU gave the hemiacetal III or its retro-Claisen ester IV, respectively, which represent structural motifs present in the closely related siphonariid polypropionates siphonarin B and baconipyrone C.