Lewis Acid-Promoted Oxidative Addition of Thioimidates to Pd(0)

The isomeric S-methyldihydropyrrins 9-Z and 9-E exhibit markedly different behavior in Pd(0)-catalyzed cross-coupling reactions. Thioimidates 9-Z are readily converted to imines 10-Z employing Pd(0)/AlkZnI. Under identical conditions 9-E are inert. Oxidative addition to Pd(0) requires activation by Zn or other Lewis acids, which is sterically unfavorable with 9-E. Analogous results were obtained with the related thioimidates 11-E,Z as well as with methylthiopyridines 19α−γ. In the case of both 11 and 19 oxidative addition to Pd(0) was greatly facilitated in the presence of BF3·Et2O. The importance of Lewis acid activation to Pd(0) oxidative addition in such substrates appears to be a general phenomenon not previously recognized

Synthesis of 1,2,3,7,8,9-Hexahydrodipyrrins and Secocorrins:^† Important Precursors for the Construction of Corrins

Hexahydrodipyrrins 15 (X = H2) have been prepared by two routes:  Pd(0)-initiated coupling/cyclization of triflates 11 and alkyne amines 12 and reduction of semicorrins 26 (X = O)

Total Syntheses of (±)- and (−)-Stemoamide

(±)-Stemoamide (1) was prepared in seven steps beginning with γ-chlorobutryl chloride (20) and succinimide (15), which were efficiently converted to the key alkyne oxazole 17 on a multigram scale. Intramolecular (Diels−Alder)−(retro-Diels−Alder) reaction of 17 then gave butenolide 12b directly upon aqueous workup. The remaining two stereocenters in 1 were established in a single step by a highly selective reduction of 12b (NaBH4/NiCl2), followed by equilibration to the thermodynamically favored natural configuration. In analogous fashion (−)-stemoamide (1) was prepared beginning with l-pyroglutamic acid (S-35)

Enantioselective Syntheses of Ring-C Precursors of Vitamin B₁₂. Substrate Control. A Novel Si-Assisted Elimination of Vinyl Bromides

Homochiral ring-C precursors 34 of Vitamin B12 have been prepared by Ireland−Claisen rearrangement of allyl esters 32, followed by a novel Si-assisted elimination of HBr

Enantioselective Syntheses of Ring-C Precursors of Vit. B₁₂. Reagent Control

Enelactones of the general structure S-(−)-I were prepared in three steps from alcohol 21 and acids 22 (ee ≈ 85%). Lactones S-(−)-I are versatile precursors to enelactams II of the type found in Vitamin B12

Enantioselective Syntheses of ¹³C-Labeled (2<i>R</i>)- and (2<i>S</i>)-Phytochromobilin Dimethyl Ester

(2R)- and (2S)-phytochromobilin dimethyl ester have been prepared in enantiomerically pure form, specifically 13C-labeled at C10 or C15

Iterative Synthesis of Semicorrins, Tripyrrolines, and Higher Analogues

Iterative Synthesis of Semicorrins, Tripyrrolines, and Higher Analogue

Lewis Acid-Promoted Oxidative Addition of Thioimidates to Pd(0)

The isomeric S-methyldihydropyrrins 9-Z and 9-E exhibit markedly different behavior in Pd(0)-catalyzed cross-coupling reactions. Thioimidates 9-Z are readily converted to imines 10-Z employing Pd(0)/AlkZnI. Under identical conditions 9-E are inert. Oxidative addition to Pd(0) requires activation by Zn or other Lewis acids, which is sterically unfavorable with 9-E. Analogous results were obtained with the related thioimidates 11-E,Z as well as with methylthiopyridines 19α−γ. In the case of both 11 and 19 oxidative addition to Pd(0) was greatly facilitated in the presence of BF3·Et2O. The importance of Lewis acid activation to Pd(0) oxidative addition in such substrates appears to be a general phenomenon not previously recognized

Synthesis of Porphobilinogen via a Novel Ozonide Cleavage Reaction

Porphobilinogen lactam methyl ester (3a) has been prepared in seven steps, and ∼20−30% overall yield, beginning with furfurylamine (4a). Hydrolysis of 3a following the literature procedure then gave porphobilinogen (1). A key intermediate in our synthesis of 3a is the 7-oxonorbornene derivative 7a, which was derived from 4a utilizing a tandem Johnson ortho ester Claisen rearrangement followed by intramolecular Diels−Alder cyclization (five steps, 55−65%). Interesting steric accelerating effects were observed in this sequence. Conversion of 7a to 3a was then accomplished employing a novel ozonide cleavage/oxidation reaction, which generated tetrahydrofurans 16a, 32, and 33 in the proper oxidation state for direct aminolysis to pyrrole 3a. A mechanism is proposed for the ozonide cleavage/oxidation that accounts for the observed stereoselectivity of this step

Enantioselective Syntheses of ¹³C-Labeled (2<i>R</i>)- and (2<i>S</i>)-Phytochromobilin Dimethyl Ester

(2R)- and (2S)-phytochromobilin dimethyl ester have been prepared in enantiomerically pure form, specifically 13C-labeled at C10 or C15