Synthesis of Alkynyl‐Glycinols by Lewis Acid Catalyzed Propargylic Substitution of Bis‐Imidates

Abstract

Racemic and enantioenriched alkynyl‐glycinols can be synthesized by Lewis acid catalyzed cyclization reaction of bis‐trichloracetimidates derived from alkynyl‐glycols. The cyclization proceeds selectively to give 4‐alkynyl‐oxazolines as the propargylic substitution products. Enantioenriched bis‐imidates that contain an alkyl or trimethylsilyl substituent at the acetylene gave oxazolines with complete inversion of configuration. In turn, considerable racemization was observed in the cyclization of bis‐imidates that contain a phenyl substituent. The racemization for these substrates can be suppressed by introduction of the electronegative substituent at the phenyl ring. Oxazolines prepared by bis‐imidate cyclization reaction can be readily transformed to protected alkynyl‐glycol derivatives.

C-Quaternary alkynyl glycinols via the Ritter reaction of cobalt complexed alkynyl glycols

“…Alcohols 3 and 8 were prepared according to the procedure described in the literature starting from the corresponding ketones 7. 14 Alcohols 3a, 32 3b, 33 3c, 34 3d, 34 3g, 34 3k, 14 3i,j 35 8a 14 are known in literature. 13 2-Methyl-pent-3-yne-1,2-diol (3h).…”

“…We have recently reported the synthesis of alkynyl glycinols 1 (R 1 ¼ H) via intramolecular propargylic amination of bistrichloroacetimidates derived from alkynyl glycols. 14 Our attempts to extend this approach for the synthesis of C-quaternary derivatives were not successful. As an alternative, we turned our attention to the Ritter reaction of 1,2-diols which is a known method for the synthesis oxazolines and oxazines involving carbenium ion A and nitrilium ion B intermediates.…”

Synthesis of α‐Ethynyl Glycines

“…[58] A wide range of Lewis acids, including TMSOTf, BF 3 ·Et 2 O, AlCl 3 , and FeCl 3 , were suitable for this transformation. The cyclization reaction of bis(imidate)s 108 proceeded with high regioselectivity and in good yields to provide a mixture of propargylic substitution isomers 109 and 110.…”

“…Our group has developed an approach for the synthesis of oxazolines 109 by employing a Lewis acid catalyzed propargylic substitution reaction of bis(imidate)s 108 (Scheme 34). [58] A wide range of Lewis acids, including TMSOTf, BF 3 ·Et 2 O, AlCl 3 , and FeCl 3 , were suitable for this transformation. The cyclization reaction of bis(imidate)s 108 proceeded with high regioselectivity and in good yields to provide a mixture of propargylic substitution isomers 109 and 110.…”

Ozonolysis of Alkynes—A Flexible Route to Alpha-Diketones: Synthesis of AI-2

“…The synthesis of AI-2 is shown in Scheme 2. The reaction of propynyl lithium with the TBS ether of hydroxyacetaldehyde afforded the alcohol, 12,13 Reaction of the diketone with diaminobenzene provided the known quinoxaline, which was identical to an authentic sample. 14 Treatment of the unpurified diketone with boric acid afforded AI-2.…”