Practical Synthesis of Enantiopure Spiro[4.4]nonane <i>C</i>-(2‘-Deoxy)ribonucleosides

Hartung, Ryan E.; Paquette, Leo A.

doi:10.1021/jo0480601

Cited by 19 publications

(10 citation statements)

References 32 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Limitations are therefore placed on the magnitude of these torsion angles, but not on the level of absolute structural rigidification. 9,27…”

Section: -Oxaspiro[44]nonanementioning

confidence: 99%

Stereoselective Reactions in Preparation of Chiral α-Heteraspiro[m.n]alkanes

Undheim

2015

Synthesis

View full text Add to dashboard Cite

The biological importance and wide occurrence of spirane systems in nature have stimulated studies in spirane chemistry. The fundamental spirane framework consists of two monocyclic rings linked in an orthogonal relationship by a common ring carbon. This review covers families of annular α-monoheteraspiranes starting with α-heteraspiro[2.4]heptanes and terminating with α-hetera[5.6]dodecanes; the annular heteroatoms are N, O, or S. The spirane systems are arranged according to the relative size of the two monocyclic rings with highest priority for the smaller ring, Often optically active spiranes are prepared for biological reasons by chemical modifications of natural products related to the spirane to be prepared. Chiral auxiliaries are useful in the introduction and control of stereochemistry in the construction of spiranes as intermediates in the preparation of novel amino acids and nucleosides. Another aspect of chiral spirane chemistry concerns modifications and conformational restrictions introduced in natural carbohydrates, nucleosides, and amino acids. 1 Introduction 2 Heteraspira[2.m]alkanes 3 Heteraspira[3.m]alkanes 4 Heteraspira[4.m]alkanes 5 Heteraspira[5.m]alkanes Key words α-heteraspiranes, chirons, stereoselective syntheses, spiroannulations, spirocyclic amino acids, spirocyclic nucleosides 2 Heteraspiro[2.m]alkanes 2.1 Heteraspiro[2.4]heptanes 2.1.1 4,6-Diazaspiro[2.4]heptane The Seebach chiron, tert-butyl (2S)-2-tert-butyl-3methyl-4-oxoimidazoline-1-carboxylate, was developed for the stereoselective construction of α-amino acids. 11 The chiron has also been used for the stereoselective synthesis of cyclic amino acids via a spirane. During lithiation of tertbutyl (2S)-2-tert-butyl-3-methyl-4-oxoimidazoline-1-carboxylate at the 5-position, the tert-butyl substituent effectively shields one face of the ylide from electrophilic attack. Thus acetate 1 (Scheme 1) is available from lithiated Seebach chiron and methyl α-bromoacetate. In a synthesis of 1-amino-2,2-dideuteriocyclopropane-1-carboxylic acid (4) via spirane 3, substrate 1 is stepwise lithiated by lithium

show abstract

“…Limitations are therefore placed on the magnitude of these torsion angles, but not on the level of absolute structural rigidification. 9,27…”

Section: -Oxaspiro[44]nonanementioning

confidence: 99%

Stereoselective Reactions in Preparation of Chiral α-Heteraspiro[m.n]alkanes

Undheim

2015

Synthesis

View full text Add to dashboard Cite

show abstract

“…Several synthetic approaches for the preparation of carbocyclic scaffolds are available. [1][2][3][4][5] In general, rigid spirocyclic structures provide wide variations of spatial disposition of the functional groups. Molecular rigidity is commonly regarded as an important property.…”

Section: Occurrence and Structurementioning

confidence: 99%

Preparation and Structure Classification of Heteraspiro[m.n]alkanes

Undheim¹

2014

Synthesis

View full text Add to dashboard Cite

The fundamental spirane framework consists of two monocyclic rings linked in an orthogonal relationship by a common ring atom. In spiranes with no annular heteroatom, four carbon atoms are bonded directly to the quaternary spirocarbon. The spirocarbon may be the site of a stereogenic centre and stereoisomerism. This review covers families of spiranes where one or both rings carry additional annular heteroatoms, mainly N, O or S. The heteroatoms are indicated by replacement prefixes. In general, the term 'hetera' denotes a nonspecified annulated heteroatom which may be N, O, or S. The presentation is arranged with preference for the size of the monocyclic rings and thereafter the nature of the annular heteroatoms.In general, rigid spirocyclic structures provide wide variations of spatial disposition of the functional groups. When the spirane skeleton consists of small-or medium-sized rings, a rigid structure results that also confers stiffness onto molecules in which the spirane may be embedded. The rigidity of such systems provides a stiff framework for the attachment of pharmacophoric groups, or a rigid framework for metal coordination. Reference is made to a limited number of studies of physico-chemical properties of small-ring systems. Nitrogen-containing systems are most common. 1 Introduction and Definitions 2 Heteraspiro[2.m]alkanes 3 Heteraspiro[3.m]alkanes 4 Heteraspiro[4.m]alkanes 5 Heteraspiro[5.m]alkanes

show abstract

“…At this juncture, the remaining challenge was to induce the stereoselective hydroboration of the azaspirane 15, a reaction for which there was little precedent in spirocyclic systems. 18 However, there were several reports of hydroborations of conformationally constrained cyclohexenes that led to equatorial alcohols as the major products. 10 It was thus our hope that a borane reagent would react preferentially with the conformer of 15 in which the N-carbamate moiety was in an equatorial orientation via a transition state in which the boron atom would be delivered preferentially from an equatorial trajectory to establish the requisite stereochemistry at C(8) and C (9).…”

Section: Preliminary Model Studiesmentioning

confidence: 99%

Toward the Total Synthesis of FR901483: Concise Synthesis of the Azatricyclic Skeleton

Simila

Martin

2007

J. Org. Chem.

View full text Add to dashboard Cite

A concise synthesis of the azatricyclic core of FR901483 has been accomplished using a novel strategy that involves a nucleophilic addition to an N-acyl iminium ion, a ring-closing metathesis, a diastereoselective hydroboration, and a lactone-lactam rearrangement that worked well in a preliminary model study. Extension of this approach to the synthesis of a more highly functionalized intermediate that could be transformed into (-)-FR901483 first required the development of a new protecting group, the 1-ethylallyloxycarbamate group, for amines that may be removed under mild conditions. However, because the stereoselectivity in a key step in which a functionalized allyl zinc reagent was added to an intermediate hydroxy-substituted imine was low, this route to (-)-FR901483 is no longer being pursued.

show abstract

Practical Synthesis of Enantiopure Spiro[4.4]nonane C-(2‘-Deoxy)ribonucleosides

Cited by 19 publications

References 32 publications

Stereoselective Reactions in Preparation of Chiral α-Heteraspiro[m.n]alkanes

Stereoselective Reactions in Preparation of Chiral α-Heteraspiro[m.n]alkanes

Preparation and Structure Classification of Heteraspiro[m.n]alkanes

Toward the Total Synthesis of FR901483: Concise Synthesis of the Azatricyclic Skeleton

Contact Info

Product

Resources

About

Practical Synthesis of Enantiopure Spiro[4.4]nonane C-(2‘-Deoxy)ribonucleosides

Cited by 19 publications

References 32 publications

Stereoselective Reactions in Preparation of Chiral α-Hetera­spiro[m.n]alkanes

Stereoselective Reactions in Preparation of Chiral α-Hetera­spiro[m.n]alkanes

Preparation and Structure Classification of Heteraspiro[m.n]alkanes

Toward the Total Synthesis of FR901483: Concise Synthesis of the Azatricyclic Skeleton

Contact Info

Product

Resources

About

Stereoselective Reactions in Preparation of Chiral α-Heteraspiro[m.n]alkanes

Stereoselective Reactions in Preparation of Chiral α-Heteraspiro[m.n]alkanes