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The direct ultraviolet irradiation of dimethyl benzyl phosphite (1) and dimethyl p-acetylbenzyl phosphite (8) was investigated in acetonitrile, cyclohexane, and benzene. Phosphite 1 gives predominantly the photo-Arbuzov product, dimethyl benzylphosphonate (2), in 67−81% accountability yields, based of phosphite consumed, along with minor amounts of bibenzyl (20) and dimethyl phosphite (10). The quantum yield for formation of 2 in cyclohexane, φP, is 0.43. By contrast, irradiation of phosphite 8 yields only 7−13% of photo-Arbuzov phosphonate (9) but relatively large amounts of radical diffusion products: dimethyl phosphite (10) the p-acetylbenzyl radical dimer (11); and p-acetyltoluene (12). Evidently 8, closely related to acetophenone, reacts predominantly via the triplet excited estate to generate long-lived, triplet, free-radical pairs (6 and 7a). In benzene, further products (15, 16, 17a and 17b) are identified that result from addition of the phosphinoyl radical (6) to benzene to give cyclohexadienyl...

A short and highly stereocontrolled synthesis of the potent proteasome inhibitor 3 from the (S)-threonine-derived oxazoline 4 has been developed. The synthetic sequence is summarized in Scheme 1. Aldol coupling of the zinc enolate of 4 with isobutyraldehyde and subsequent silylation provided the TBS ether 5 diastereoselectively (10:1). Reductive cleavage of the oxazoline ring of 5 followed by Swern oxidation of the resulting amino alcohol afforded amino ketone 6, converted further by N-acylation to the acrylamide 7, whose structure was confirmed by X-ray crystallographic analysis. Acrylamide 7 was cyclized to 8 by a novel application of the Kulinkovich Ti(II)-cyclopentene complex. Silylation of 8 to 9 and radical cyclization at low temperature produced the bicyclic lactam 10 with complete control of all stereocenters. Hydroxy desilylation and N-deprotection of 10 gave the dihydroxy ester 11, which was converted to 3 by a novel three-step sequence: (1) demethylation with [Me2AlTeMe]2, (2) combined beta-lactonization and chlorination, and (3) desilylation to effect cleavage of the TBS ether.

The first total synthesis of the marine dolabellane diterpene (+)-4,5-deoxyneodolabelline (1) has been accomplished. The highly efficient approach is characterized by the convergent assembly of dihydropyrans 2ab and cyclopentylsilanes 3ab. Allylic silane 3a was prepared from 2-methyl-2-cyclopentenone via a copper-catalyzed 1,4-addition followed by diastereoselective alkylation of the resulting enolate. A chemical resolution of racemic cyclopentanone 8 was effected by (S)-CBS-catalyzed borohydride reduction. Direct hydroxymethylation of the enantioenriched ketone 8 to form allylic alcohol 14 was achieved by a Stille palladium-catalyzed cross-coupling from the cyclopentenyl triflate 13. Treatment of the corresponding allylic phosphate 15 with trimethylsilylcopper reagent provided for displacement with allylic transposition yielding the exocyclic allylsilane 3a with excellent diastereoselectivity. Dihydropyrans 2a and 2b were prepared from optically pure acyclic acetals via ring-closing metathesis. Coupling of 3a and 2a or 2b via the carbon-Ferrier protocol gave trans-2,6-disubstituted dihydropyrans 30 and 35 with complete stereoselectivity. Vanadium-based pinacol coupling reactions were explored for closure of the medium-sized carbocycle to yield syn-diol 33. X-ray diffraction studies of the monobenzoate 34 have provided unambiguous stereochemical assignments. Substantial ring strain accounted for the lack of alkene products typical of reductive elimination using TiCl(3) and zinc-copper couple (McMurry) conditions leading to 37. Finally, the natural product 1 was obtained via Swern oxidation of the diol 37.

The oxidation of alcohols into their corresponding carbonyl compounds represents a fundamentally important functional group transformation and occupies a prominent position in modern synthetic organic chemistry. Advances on the development of new oxidation reagents and methodologies and their applications in both targetand diversity-oriented synthesis have been regularly surveyed and constituted one of the most extensively and actively investigated areas of current organic synthesis. In this context, a plethora of oxidants, including those small organic molecule-based reagents (such as Dess-Martin periodinane, Swern oxidation, Moffatt oxidation, Corey-Kim oxidation, and SO3/pyridine) and metal-based systems (such as Jones reagent, Collins reagent, pyridinium chlorochromate, pyridinium dichromate, barium permanganate, manganese dioxide, ruthenium tetroxide, silver carbonate, and Oppenauer oxidation), have been identified to be powerful tools promoting conversion of various alcohols into their corresponding aldehyde or ketone products and thus evolved as a most important class of tools in synthetic chemists’ arsenal. A recent conceptually novel approach in alcohol oxidation chemistry, driven by the needs of process environmental compatibility and sustainability, has been exploring aerobic oxidation with highly active transition-metal catalysts (such as Pd, Ru, Fe, Cu, Pt, Au, Ir, Rh, etc.) and dioxygen gas as the terminal oxidant, their heterogeneously immobilized variants, and biomimetic systems. Despite these impressive advances, very few of the known methods are capable of offering truly economic and practical oxidation transformations across a broad spectrum of alcohol substrates. Many of these systems suffered from high reagent cost, air instability, employment of heavy metals or organic oxidants, stringent reaction conditions, operational complexity, functional group incompatibility, or production of wastes in their related processes. Thus, there is a continuing and increasing demand for new reagents that could help address the above-mentioned challenges. We herein report on an exceedingly simple secondary alcohol oxidation protocol that employs the widely available sodium hydride (NaH) as the oxidant.