Synthesis of Enantiopure 3-Azabicyclo[3.2.0]heptanes by Diastereoselective Intramolecular [2+2] Photocycloaddition Reactions on Chiral Perhydro-1,3-benzoxazines

Abstract

[2+2] photocycloadditions involving chiral 3-acryloyl-2-vinylperhydro-1,3-benzoxazines derived from (-)-8-aminomenthol are highly diastereoselective reactions. The facial selectivity depends on the type of substitution at the vinyl double bond, and always leads to cis-fused bicyclic derivatives. The de is good for compounds with one substituent at the outer carbon of the double bond at C-2, but only one diastereomer is formed in cyclizations of compounds with two substituents at that position. The elimination of the menthol appendage gives enantiopure 3-azabicyclo[3.2.0]heptanes.

Synthesis of Enantiopure Oxygen‐ and Nitrogen‐Containing Heterocycles by Diastereoselective Ring‐Closing Metathesis Reaction in Perhydro‐1,3‐benzoxazine Derivatives

“…Similarly, tetrahydro-1H-azepines can be prepared by DSRCM reaction of trienes 19 c, 20 c, 21 c, 20 d and 21 d (entries [12][13][14][15][16][17][18][19][20][21][22]. Again, the best results in terms of stereoselectivity were achieved when the hydroxyl group was protected as methyl ether if the diastereotopic olefin chains are 1,1-disubstituted entries 14 and 15) or as tert-butyldimethylsilyl ether if the diastereotopic olefin chains are monosubstituted (entries 21 and 22).…”

“…[16] The absolute configuration of the newly created stereocenters in 24 e was determined by its conversion into the aminomenthol derivatives 28 by nucleophilic ring opening of the N,O-acetal moiety by aluminum hydride (Scheme 6) and X-ray diffraction analysis. In a similar way, the absolute configuration of the other RCM reaction products of Table 2 and 34 and the hexahydroazocine 32 was performed in three steps, [22] as depicted in Scheme 7. In a similar way, the absolute configuration of the other RCM reaction products of Table 2 and 34 and the hexahydroazocine 32 was performed in three steps, [22] as depicted in Scheme 7.…”

“…In a similar way, the absolute configuration of the other RCM reaction products of Table 2 was assigned. Methylation of 22 c provided 24 c, while deprotection of tert-butyldimethylsilyl ether in 27 c furnished alco- and 34 and the hexahydroazocine 32 was performed in three steps, [22] as depicted in Scheme 7. The reductive ring-opening of the N,O-acetal moiety by treatment with aluminium hydride generated in situ from lithium aluminium hydride and aluminium chloride, in THF at room temperature led to amino menthol derivatives in good to excellent yields.…”

Regio‐ and Stereoselective Synthesis of Bicyclic Limonene‐Based Chiral Aminodiols and Spirooxazolidines

“…A large number of natural products such as α‐ and β‐pinene, 2‐ and 3‐carene, and (+)‐pulegole serve as important starting materials for the synthesis of bi‐ and trifunctional chiral compounds and heterocycles. Monoterpene‐based 1,2‐ and 1,3‐amino alcohols have been demonstrated to be excellent chiral auxiliaries in a wide range of stereoselective transformations, including intramolecular radical cyclizations, intramolecular [2+2] photocycloaddition, and Grignard addition …”

“…[1][2][3] Al arge number of natural products such as a-a nd b-pinene, [4][5][6] 2-and 3-carene, [7,8] and (+ +)-pulegole [9,10] serve as important startingm aterials fort he synthesis of bi-and trifunctional chiral compounds and heterocycles. Monoterpene-based 1,2-and 1,3-amino alcohols have been demonstrated to be excellent chiral auxiliaries in aw ide range of stereoselective transformations, including intramolecular radical cyclizations, [11] intramolecular [2+ +2] photocycloaddition, [12] and Grignard addition. [13,14] Furthermore,a minodiols, combining the chemical properties of 1,2-and 1,3-amino alcohols derived fromn aturally occurring terpenes, are excellent startingm aterials and catalysts of stereoselectives ynthesis.…”