Diastereoselective Synthesis of Unsaturated Vicinal Amino Alcohols via Diels-Alder Reactions of iV-Sulfinyl Dienophiles

Ravi S. Garigipati, Alan J. Freyer, Robert R. Whittle, Steven M. Weinreb

Research output: Contribution to journalArticle

80 Citations (Scopus)

Abstract

A novel diastereoselective route for the synthesis of α-hydroxy-β,γ-unsaturated amine derivatives is described. The protocol starts with a 3,6-dihydrothiazine 1-oxide, which is obtained stereoselectively by a Diels-Alder [4 + 2] cycloaddition of a N-sulfinyl dienophile and a 1,3-diene of known geometry. Fission of the S-N bond of the adduct with a Grignard reagent leads to an allylic sulfoxide which is converted stereoselectively to an allyl alcohol via an allylic sulfoxide/sulfenate ester [2,3]-sigmatropic rearrangement. (E,E)-2,4-Hexadiene (4) and (E,Z)-2,4-hexadiene (7) were stereoselectively transformed to threo amino alcohol (9) and erythro amino alcohol (11), respectively. Intermediates in these transformations have been investigated by 1H NMR experiments. The configuration and conformation of Diels-Alder adduct 5a have been determined by X-ray crystallography and 1H NMR lanthanide induced shift experiments. A variation of this strategy incorporating intramolecular N-sulfinyl Diels-Alder reactions has been used in total synthesis of the sphingolipid bases erythro- and threo-sphingosine. (E,E)-Diene carbamate 31 was converted to threo-sphingosine (25) in four steps in 52% overall yield. Similarly, (E,Z)-diene carbamate 46 was transformed to erythro-sphingosine (27) in 55% overall yield. Interestingly, the N-sulfinyl compound obtained from (E,Z)-diene carbamate 39 did not cyclize, probably for conformational reasons.

Original languageEnglish (US)
Pages (from-to)7861-7867
Number of pages7
JournalJournal of the American Chemical Society
Volume106
Issue number25
DOIs
StatePublished - Dec 1 1984

Fingerprint

Sphingosines
sulfoxide
Amino alcohols
Amino Alcohols
Carbamates
Cycloaddition Reaction
Sphingosine
Nuclear magnetic resonance
Lanthanoid Series Elements
Sphingolipids
Cycloaddition
X ray crystallography
X Ray Crystallography
Rare earth elements
Oxides
Amines
Conformations
Esters
Alcohols
Experiments

All Science Journal Classification (ASJC) codes

  • Catalysis
  • Chemistry(all)
  • Biochemistry
  • Colloid and Surface Chemistry

Cite this

Garigipati, Ravi S. ; Freyer, Alan J. ; Whittle, Robert R. ; Weinreb, Steven M. / Diastereoselective Synthesis of Unsaturated Vicinal Amino Alcohols via Diels-Alder Reactions of iV-Sulfinyl Dienophiles. In: Journal of the American Chemical Society. 1984 ; Vol. 106, No. 25. pp. 7861-7867.
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abstract = "A novel diastereoselective route for the synthesis of α-hydroxy-β,γ-unsaturated amine derivatives is described. The protocol starts with a 3,6-dihydrothiazine 1-oxide, which is obtained stereoselectively by a Diels-Alder [4 + 2] cycloaddition of a N-sulfinyl dienophile and a 1,3-diene of known geometry. Fission of the S-N bond of the adduct with a Grignard reagent leads to an allylic sulfoxide which is converted stereoselectively to an allyl alcohol via an allylic sulfoxide/sulfenate ester [2,3]-sigmatropic rearrangement. (E,E)-2,4-Hexadiene (4) and (E,Z)-2,4-hexadiene (7) were stereoselectively transformed to threo amino alcohol (9) and erythro amino alcohol (11), respectively. Intermediates in these transformations have been investigated by 1H NMR experiments. The configuration and conformation of Diels-Alder adduct 5a have been determined by X-ray crystallography and 1H NMR lanthanide induced shift experiments. A variation of this strategy incorporating intramolecular N-sulfinyl Diels-Alder reactions has been used in total synthesis of the sphingolipid bases erythro- and threo-sphingosine. (E,E)-Diene carbamate 31 was converted to threo-sphingosine (25) in four steps in 52{\%} overall yield. Similarly, (E,Z)-diene carbamate 46 was transformed to erythro-sphingosine (27) in 55{\%} overall yield. Interestingly, the N-sulfinyl compound obtained from (E,Z)-diene carbamate 39 did not cyclize, probably for conformational reasons.",
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Diastereoselective Synthesis of Unsaturated Vicinal Amino Alcohols via Diels-Alder Reactions of iV-Sulfinyl Dienophiles. / Garigipati, Ravi S.; Freyer, Alan J.; Whittle, Robert R.; Weinreb, Steven M.

In: Journal of the American Chemical Society, Vol. 106, No. 25, 01.12.1984, p. 7861-7867.

Research output: Contribution to journalArticle

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T1 - Diastereoselective Synthesis of Unsaturated Vicinal Amino Alcohols via Diels-Alder Reactions of iV-Sulfinyl Dienophiles

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N2 - A novel diastereoselective route for the synthesis of α-hydroxy-β,γ-unsaturated amine derivatives is described. The protocol starts with a 3,6-dihydrothiazine 1-oxide, which is obtained stereoselectively by a Diels-Alder [4 + 2] cycloaddition of a N-sulfinyl dienophile and a 1,3-diene of known geometry. Fission of the S-N bond of the adduct with a Grignard reagent leads to an allylic sulfoxide which is converted stereoselectively to an allyl alcohol via an allylic sulfoxide/sulfenate ester [2,3]-sigmatropic rearrangement. (E,E)-2,4-Hexadiene (4) and (E,Z)-2,4-hexadiene (7) were stereoselectively transformed to threo amino alcohol (9) and erythro amino alcohol (11), respectively. Intermediates in these transformations have been investigated by 1H NMR experiments. The configuration and conformation of Diels-Alder adduct 5a have been determined by X-ray crystallography and 1H NMR lanthanide induced shift experiments. A variation of this strategy incorporating intramolecular N-sulfinyl Diels-Alder reactions has been used in total synthesis of the sphingolipid bases erythro- and threo-sphingosine. (E,E)-Diene carbamate 31 was converted to threo-sphingosine (25) in four steps in 52% overall yield. Similarly, (E,Z)-diene carbamate 46 was transformed to erythro-sphingosine (27) in 55% overall yield. Interestingly, the N-sulfinyl compound obtained from (E,Z)-diene carbamate 39 did not cyclize, probably for conformational reasons.

AB - A novel diastereoselective route for the synthesis of α-hydroxy-β,γ-unsaturated amine derivatives is described. The protocol starts with a 3,6-dihydrothiazine 1-oxide, which is obtained stereoselectively by a Diels-Alder [4 + 2] cycloaddition of a N-sulfinyl dienophile and a 1,3-diene of known geometry. Fission of the S-N bond of the adduct with a Grignard reagent leads to an allylic sulfoxide which is converted stereoselectively to an allyl alcohol via an allylic sulfoxide/sulfenate ester [2,3]-sigmatropic rearrangement. (E,E)-2,4-Hexadiene (4) and (E,Z)-2,4-hexadiene (7) were stereoselectively transformed to threo amino alcohol (9) and erythro amino alcohol (11), respectively. Intermediates in these transformations have been investigated by 1H NMR experiments. The configuration and conformation of Diels-Alder adduct 5a have been determined by X-ray crystallography and 1H NMR lanthanide induced shift experiments. A variation of this strategy incorporating intramolecular N-sulfinyl Diels-Alder reactions has been used in total synthesis of the sphingolipid bases erythro- and threo-sphingosine. (E,E)-Diene carbamate 31 was converted to threo-sphingosine (25) in four steps in 52% overall yield. Similarly, (E,Z)-diene carbamate 46 was transformed to erythro-sphingosine (27) in 55% overall yield. Interestingly, the N-sulfinyl compound obtained from (E,Z)-diene carbamate 39 did not cyclize, probably for conformational reasons.

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