Variable Strategy toward Carbasugars and Relatives. 1. Stereocontrolled Synthesis of Pseudo-β-d-gulopyranose, Pseudo-β-d-xylofuranose, (Pseudo-β-d-gulopyranosyl)amine, and (Pseudo-β-d-xylofuranosyl)amine

Abstract

Four novel, chiral nonracemic carbasugars have been synthesized from 1,2-O-isopropylidene-D-glyceraldehyde. Furan- and pyrrole-based 2-silyloxy dienes--mimics of the alpha,gamma-dianions of gamma-hydroxy- and gamma-aminobutanoic acid, respectively--nicely served to complete the syntheses of two all-oxygen compounds, pseudo-beta-D-gulopyranose and pseudo-beta-D-xylofuranose, and two "anomeric" amino derivatives, (pseudo-beta-D-gulopyranosyl)amine (1,2,4-tri-epi-validamine) and (pseudo-beta-D-xylofuranosyl)amine. Two sequential, highly diastereoselective carbon-carbon bond-forming maneuvers, i.e., a vinylogous crossed aldol addition and an intramolecular aldolization, proved central to these constructions. The fact that readily available heterocyclic diene scaffolds can be employed in the assembly of a varied repertoire of carbasugars and analogues widens the prospects of dienoxy silane chemistry.

Variable Strategy toward Carbasugars and Relatives. 2.1 Diversity-Based Synthesis of β-d-Xylo, β-d-Ribo, β-l-Arabino, and β-l-Lyxo 4a-Carbafuranoses and (4a-Carbafuranosyl)thiols

“…Overall, the two carbasugars 1 10 and 2 11 were thus available in eight individual steps (from 10 ) and 38% and 32% yields, respectively, compared to our previous route to 1 of eight steps and 20% overall yield …”

“…The original goal of our research was to implement a diversity-based plan directed toward the synthesis of carbasugar constructs and to demonstrate its genuine effectiveness, variability, and applicability. Having completed the synthesis of four representatives of the 4a-carbafuranose family ( 1 − 4 ) and of four sulfur-containing congeners ( 5 − 8 ), we have certified that the synthetic plan does indeed meet these important requisites. , Central to the success of this endeavor was the discovery of a novel, high-yielding silylative cycloaldolization, whose application allowed us to remedy the major problem of the previous synthesis, which lay in the low efficiency and reproducibility of the LDA-promoted aldol annulation.…”

“…We are pleased to report here a significant improvement in conjoining the carbon adjacent to the lactone carbonyl of 13 (C2) to its aldehyde terminal (C6), thereby permitting installation of the carbafuranose ring. During our earlier studies, this ring-forming event was conducted by briefly exposing 13 to LDA and led to the cycloaldolization product in, at best, a modest 30−50% yield, albeit with excellent diastereoselectivity. We considered improvement in the construction of the cyclitol ring a prime task if a truly efficient and scalable synthesis was to be pursued.…”

“…In the first work of this series, we described the results of a study that demonstrated how varied heterocyclic dienoxy silane synthons can be used to assemble a small collection of chiral nonracemic carbafuranose and carbapyranose compounds, including 5a-carba-β- d -gulopyranose, 5a-carba-β- d -xylofuranose, (5a-carba-β- d -gulopyranosyl)amine, and (5a-carba-β- d -xylofuranosyl)amine. Crucial to the success of these syntheses were two sequential carbon−carbon bond-forming constructions, an intermolecular vinylogous aldolization between a dienoxy silane donor and a suitable aldehyde acceptor, followed by a regio- and diastereoselective cycloaldolization that installs the cyclitol frame (vide infra).…”

Synthesis of 8-Desbromohinckdentine A1

“…Amine 32 was acylated, first to yield 33 , and a second time to yield 34 . Although there is good literature precedent, we were unsuccessful in bringing about the formation of aldol 35 . Amide 34 was consumed, but cyclization products could not be detected.…”