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. 2014 Jan 1;88(2):1233-1254.
doi: 10.3987/COM-13-S(S)88.

SYNTHESIS OF DE NOVO CHIRAL γ-AMINO-YNAMIDES USING LITHIATED YNAMIDES. OBSERVATION OF A UNIQUE 5- ENDO-DIG CYCLIZATION WITH AN INVERSION OF S-CENTER

Xiao-Na Wang  1 , Richard P Hsung  1 , Sierra K Fox  1 , Ming-Can Lv  1 , Rui Qi  1
Affiliations

SYNTHESIS OF DE NOVO CHIRAL γ-AMINO-YNAMIDES USING LITHIATED YNAMIDES. OBSERVATION OF A UNIQUE 5- ENDO-DIG CYCLIZATION WITH AN INVERSION OF S-CENTER

Xiao-Na Wang et al. Heterocycles. .

Abstract

We describe herein details of our efforts in developing a highly stereoselective synthesis of de novo chiral γ-amino-ynamides through additions of lithiated ynamides to Ellman-Davis chiral N-tert-butanesulfinyl imines. While additions of ynamides could be highly stereoselective even without Lewis acids, the use of BF3-OEt2 completely reversed the stereoselectivity. On the other hand, additions of oxazolidinone-substituted, oxazinanone-substituted and tetrahydropyrimidinone-substituted ynamides behaved quite differently and functioned better with BF3-OEt2. The chirality of the oxazolidinone ring exerts no impact on the selectivity. This work also features a unique 5-endo-dig cyclization of oxazolidinone-substituted γ-amino-ynamides that could be promoted with acid, leading to isothiazoles and 2,3-dihydro-isothiazole S-oxides.

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Figures

Figure 1
Figure 1
X-Ray structure of 14-S [CCDC 955979]
Figure 2
Figure 2
Chelation-TS versus open-TS [synclinal and anti-periplanar]
Figure 3
Figure 3
X-Ray structures of 26-R and 31 [CCDC 955980 and 955981]
Figure 4
Figure 4
X-Ray structure of 33 [CCDC 955982]
scheme 1
scheme 1
Efficient syntheses of chiral γ-amino-ynamides
scheme 2
scheme 2
A comparison of the two synthetic approaches
scheme 3
scheme 3
Addition of lithiated ynamides to chiral N-tert-butanesulfinyl iminesa,b
scheme 4
scheme 4
Addition of lithiated ynamides to chiral N-tert-butanesulfinyl imines with BF3-OEt2a,b
scheme 5
scheme 5
Acid-promoted 5-endo-dig cyclization of ynamides 27-R, 30-R, and 31
See this image and copyright information in PMC

References

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