Synthesis of acyldodecaheterocycles derived from (1R)-(–)-myrtenal and evaluation as chiral auxiliaries

New (1R)-(–)-myrtenal-derived macrocycles 5a and 5b were efficiently used as chiral auxiliaries in the diastereoselective nucleophilic addition of several nucleophiles (RMgX, RLi, LiAlH4, and NaBH4). We observed that the diastereoselectivity depended on the nucleophile, with the stereoselectivity order being RMgX (>99:1 dr) > RLi (7:3 dr) > AlLiH4 ⩾ NaBH4 (6:4 dr). The absolute configuration of the resulting carbinols was established by X-ray diffraction of adducts 9a and 9b, and through chemical correlation of carbinols 9b and 9c with diols of known absolute configuration.

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(1S,2R,8R,9S,11R,13S,17S,19R)-4,6-Dioxa-14,16-dithia-5-benzoyl-10,10,20,20-tetramethylpentacyclo-[17.1.1.19,11.02,17.08,13]-docosaneC29H40O3S2dr >99% (by 1H NMR)[α]D25=+294.5 (c 0.49, CHCl3)Source of chirality: (1R)-(–)-myrtenalAbsolute configuration: (1S,2R,8R,9S,11R,13S,17S,19R)

(1S,2R,8R,9S,11R,13S,17S,19R)-4,6-Dioxa-14,16-dithia-5-acetyl-10,10,20,20-tetramethylpentacyclo-[17.1.1.19,11.02,17.08,13]-docosaneC24H38O3S2dr >99% (by 1H NMR)[α]D25=+324.9 (c 0.40, CHCl3)Source of chirality: (1R)-(–)-myrtenalAbsolute configuration: (1S,2R,8R,9S,11R,13S,17S,19R)

(1S,2R,8R,9S,11R,13S,17S,19R)-4,6-Dioxa-14,16-dithia-5-[(S)-1-phenyleth-1-yl-1-ol]-10,10,20,20-C30H44O3S2dr >99:1 (by 1H NMR)[α]D25=+163 (c 0.10, CHCl3)Source of chirality: (1R)-(–)-myrtenalAbsolute configuration: (1S,2R,8R,9S,11R,13S,17S,19R)

(1S,2R,8R,9S,11R,13S,17S,19R)-4,6-Dioxa-14,16-dithia-5-[(S)-1-phenylpro-1-yl-1-ol]-10,10,20,20-tetramethylpentacyclo-[17.1.1.19,11.02,17.08,13]-docosaneC31H46O3S2dr >99:1 (by 1H NMR)[α]D25=+242 (c 0.10, CHCl3)Source of chirality: (1R)-(–)-myrtenalAbsolute configuration: (1S,2R,8R,9S,11R,13S,17S,19R)

(1S,2R,8R,9S,11R,13S,17S,19R)-4,6-Dioxa-14,16-dithia-5-[(S)-1,2-diphenyleth-1-yl-1-ol]-10,10,20,20-tetramethylpentacyclo-[17.1.1.19,11.02,17.08,13]-docosaneC36H48O3S2dr >99:1 (by 1H NMR)[α]D25=+196 (c 0.20, CHCl3)Source of chirality: (1R)-(–)-myrtenalAbsolute configuration: (1S,2R,8R,9S,11R,13S,17S,19R)

(1S,2R,8R,9S,11R,13S,17S,19R)-4,6-Dioxa-14,16-dithia-5-[(S)-1,3-diphenyl-2-propyn-1-yl-1-ol]-10,10,20,20-tetramethylpentacyclo-[17.1.1.19,11.02,17.08,13]-docosaneC37H46O3S2dr >99:1 (by 1H NMR)[α]D25=+247 (c 0.23, CHCl3)Source of chirality: (1R)-(–)-myrtenalAbsolute configuration: (1S,2R,8R,9S,11R,13S,17S,19R)

(1S,2R,8R,9S,11R,13S,17S,19R)-4,6-Dioxa-14,16-dithia-5-[(S)-1-phenyl-2-propyn-1-yl-1-ol]-10,10,20,20-tetramethylpentacyclo-[17.1.1.19,11.02,17.08,13]-docosaneC31H42O3S2dr >99:1 (by 1H NMR)[α]D25=+180.3 (c 0.35, CHCl3)Source of chirality: (1R)-(–)-myrtenalAbsolute configuration: (1S,2R,8R,9S,11R,13S,17S,19R)

(1S,2R,8R,9S,11R,13S,17S,19R)-4,6-Dioxa-14,16-dithia-5-[(S)-1-phenyl-2-propen-1-yl-1-ol]-10,10,20,20-tetramethylpentacyclo-[17.1.1.19,11.02,17.08,13]-docosaneC31H44O3S2dr >99:1 (by 1H NMR)[α]D25=+236 (c 0.050, CHCl3)Source of chirality: (1R)-(–)-myrtenalAbsolute configuration: (1S,2R,8R,9S,11R,13S,17S,19R)

(1S,2R,8R,9S,11R,13S,17S,19R)-4,6-Dioxa-14,16-dithia-5-[(R)-1-phenyleth-1-yl-ol]-10,10,20,20-tetramethylpentacyclo-[17.1.1.19,11.02,17.08,13]-docosaneC30H44O3S2dr >99:1 (by 1H NMR)[α]D25=+333 (c 0.33, CHCl3)Source of chirality: (1R)-(–)-myrtenalAbsolute configuration: (1S,2R,8R,9S,11R,13S,17S,19R)

(1S,2R,8R,9S,11R,13S,17S,19R)-4,6-Dioxa-14,16-dithia-5-[(R)-1-phenylprop-2-yl-2-ol]-10,10,20,20-tetramethylpentacyclo-[17.1.1.19,11.02,17.08,13]-docosaneC31H46O3S2dr >90:10 (by 1H NMR)[α]D25=+269 (c 0.28, CHCl3)Source of chirality: (1R)-(–)-myrtenalAbsolute configuration: (1S,2R,8R,9S,11R,13S,17S,19R)

(S)-2-Phenyl-3-butene-1,2-diolC10H12O2dr >90%ee (by 1H NMR)[α]D22=+6.7 (c 0.30, EtOH)Source of chirality: (1R)-(–)-myrtenalAbsolute configuration: (2S)

(S)-2,3-Diphenyl-propane-1,2-diolC15H16O2dr >90%ee (by 1H NMR)[α]D21=+56.7 (c 0.18, EtOH)Source of chirality: (1R)-(–)-myrtenalAbsolute configuration: (2S)