William H. Miles

Enantioselective synthesis of (S)- and (R)-fluoxetine hydrochloride

Abstract The enantioselective synthesis of fluoxetine hydrochloride, a potent serotonin-uptake inhibitor, is described. The synthesis of (S)-fluoxetine hydrochloride begins with the asymmetric carbonyl-ene reaction of benzaldehyde with 3-methylene-2,3-dihydrofuran (1) catalyzed by Ti[OCH(CH3)2]4/(S)-BINOL to give (S)-2-(3-furyl)-1-phenyl-1-ethanol (2) in 90% yield and 95% ee. In five steps, alcohol 2 was converted into (S)-fluoxetine hydrochloride (97% ee and 56% overall yield from benzaldehyde). (R)-fluoxetine hydrochloride was prepared by the same sequence except that Ti[OCH(CH3)2]4/(R)-BINOL was used in the first reaction to give the enantiomer of 2.

A formal synthesis of (+)-juvabione

Abstract A formal synthesis of (+)-juvabione is presented based on the diastereoselective addition of the enolate of N-acyloxalidinone 3 with η p6 -(C 6 H 5 OC 6 H 5 )Mn(CO) 3 BF 4 .

The Reduction of Nitrobenzenes by Triethylsilane Using Wilkinson's Catalyst

Abstract Aromatic nitro compounds are effectively reduced to anilines by triethylsilane using Wilkinsons catalyst.

The preparation of α-methoxyalkyliron complexes: precursors of secondary carbeneiron complexes

Abstract The addition of methyl-, n-butyl-, phenyl-, and p-tolyl-lithium reagents to (C5H5)(CO)2FeCHOCH3+ PF6+ gives the respective α-methoxyalkyliron complexes in good yield. The addition of vinyllithium or vinylmagnesium bromide to (C5H5)(CO)2FeCHOCH3+ PF6− yields rearranged product cis-(C5H5)(CO)2- FeCH2CHCHOCH3.

Furan Approach to Vitamin D Analogues. Synthesis of the A-Ring of Calcitriol and 1α-Hydroxy-3-deoxyvitamin D3

The A-rings of calcitriol (1α,25-dihydroxyvitamin D(3)) and 1α-hydroxy-3-deoxyvitamin D(3) were synthesized using the furan approach. The critical steps in the synthesis of the A-ring of calcitriol involved an asymmetric carbonyl-ene reaction of 3-methylene-2,3-dihydrofuran with 3-(tert-butyldimethylsiloxy)propanal, a diastereoselective Friedel-Crafts hydroxyalkylation, an oxidation of the 2,3-disubstituted furan to give a γ-hydroxybutenolide, and a Peterson olefination. The A-ring (Z)-dienol of calcitriol was synthesized in 12 steps from 3-(tert-butyldimethylsiloxy)propanal in 17% yield.

Synthesis and ene reactions of 3-methylene-2,3-dihydrofuran

Abstract The unexpected formation of 3-methylene-2,3-dihydrofuran 1 using the Huang-Minlon modification of the Wolff-Kishner reduction of 3-furaldehyde is discribed. Furan 1 readily undergoes ene reactions with simple electron-deficient alkenes.

Furan approach to the synthesis of the A-ring of Vitamin D analogues

The efficient transformation of 2,3-disubstituted furan (3) into (Z)-dienol (2) illustrates a useful strategy for the synthesis of the A-ring of Vitamin D analogues.

The ene reaction of 3-methylene-2,3-dihydrofuran with aldehydes

Abstract The Lewis acid-promoted ene reaction of 3-methylene-2,3-dihydrofuran, 1, with aldehydes gives the corresponding alcohols in good to excellent yield.

Diastereoselective reactions of a simple secondary grignard reagent

Abstract The stereoselective reactions of a simple acyclic Grignard reagent CH 3 CH(OR)CH 2 CH(CH 3 )MgX, 2, with several electrophiles are described.

Reactions of a cationic bridging methylidyne-iron complex with carbon monoxide and with alkenes

Abstract The bridging methylene diiron compound (C5H5)2Fe2(CO)2(μ-CO)-(μ-CH2), 1, reacts with (C6H5)3C+PF6- to produce [(C5H5)2Fe2(CO)2(μ-CO)-(μ-CH)]+ PF6−, 4, the first methylidyne complex in which a CH unit bridges between two metals. Methylidyne complex 4 reacts with CO to produce the bridging acylium complex [(C5H5)2Fe2(CO)2(μ-CO)(μ-CHCO)]+PF6−, 7. Methylidyne complex 4 reacts with ethylene to add its μ-CH bond across the carbon-carbon double bond of ethylene to give the propylidyne complex [(C5H5)2Fe2(CO)2(μ-CO)-(μ-C2CH3)]+ PF6−, 11. Reaction of 1,2-disubstituted alkenes with 4 leads to the formation of equilibrating mixtures of bridging alkylidyne complexes and bridging vinyl complexes.