Highly Diastereoselective Ring-Opening Reactions of Chiral Acetals with Secondary or Sterically Hindered Grignard Reagents

Abstract

1,4-Di-tert-alkoxy-(2S,3S)-2,3-butanediols 2 were obtained from the reactions of 2S,BS-threitol bisketals with Grignard reagents. The reactions of benzylic acetals 3, prepared from 1,4-di-tertalkoxy-(2S,3S)-2,3-butanediols and aromatic aldehydes, with aryl or secondary or sterically hindered Grignard reagents give the corresponding ring-opening products 4 in high diastereoselectivity.There has been an increasing interest in the stereoselective ring opening of acetals by means of nucleop h i l e~.~-~ Most of these approaches involve the preferential complex formation of acetals with a Lewis acid and subsequent invertive substitution by nucleophiles (Scheme 1).2 The retentive ring cleavage of acetals has been investigated only briefly, mostly related to the reductive ring opening with metalRecently, Yamamoto and his co-workers reported the highly diastereoselective retentive alkylation of chiral acetals using novel organoaluminum reagent^.^ However, only methyl-or primary alkylaluminum reagents can be used. We now wish to describe our investigations on the highly diastereoselective reactions of secondary or sterically bulky Grignard reagents with chiral acetals prepared from aldehydes and tunable chiral diols. Results and DiscussionWe recently reported a chelation-assisted regioselective alkylative cleavage of cyclic ketals with Grignard rea g e n t~.~ By using this strategy, 1,4-di-tert-alkoxy-(2S,3S)-2,3-butanediols 2 were easily accessible from the corresponding L-tartaric acid-based bisketals 1.6 Diols 2 might demonstrate certain unique properties to serve as a ligand in asymmetric reactions. First, the size of the alkoxy substituents can be tuned. Second, the oxygen atom in the alkoxy substituent can act as an additional ligand for complexation with the metallic species which would result in the enhancement of the stereoselectivity of the reaction. Such complexation has been shown to be extremely important to direct the regioselective alkylative ring opening of a~etonides.~ On the basis of this @ Abstract published in Advance ACS Abstracts, November 15,1994. (1) For a recent review, see: Alexakis, A.; Mangeney, P. Mori, A.; Arai, I.; Yamamoto, H. Tetrahedron Lett. 1986, 26, 983. (c) Mori, A.; Fujiwara, J.; Maruoka, K.; Yamamoto, H. J. Organomet. Chem. 1986,285, 83. (d) Mori, A.; Fujiwara, J.; Maruoka, K.; Yamamoto, H. Tetrahedron Lett. 1983,24, 4581.(4) (a) Ishihara, K.; Hanaki, N.; Yamamoto, H. conjecture, we felt that this advantage could be made use of in the diastereoselective ring-opening reactions of chiral acetals 3 with Grignard reagents.

Chelation-Assisted C−O Bond Cleavage of Ortho Esters. A Convenient Synthesis of myo-Inositol Derivatives Having Free Hydroxy Group(s) at Specific Position(s)

“…No C−O bond cleavage at the ortho ester moiety in 13 was observed. The methoxy group in 13 apparently directs the selectivity of the ring opening reaction at the benzylidene moiety. Interestingly, the reaction is nonstereoselective and is compatible with our earlier work on the alkylative ring opening of acetals with the methyl Grignard reagent …”

“…Acetal functionality are known to undergo chelation-assisted regioselective ring opening reactions with Grignard reagents. 4d,e, The products shown in eqs 3 and 4 contain such acetal group. We felt that a one-pot process may be developed such that a convenient synthesis of inositol derivatives having two free hydroxy group at C-1 and C-3 positions can be achieved from 6 or 8 .…”

Asymmetric Induction via an Intramolecular Haloetherification Reaction of Chiral Ene Acetals: A Novel Approach to Optically Active 1,4- and 1,5-Diols

“…We next studied the nucleophilic replacement of the alkoxy group of 8a and 8d with carbon nucleophiles. Grignard reagents reacted at the acetal carbon and substitution occurred in good yields with complete retention of stereochemistry to give 9 (Table )…”

A Coumarin‐boronic Based Fluorescent “ON‐OFF” Probe for Hg2+ in Aqueous Solution

“…If the mercury ion was discharged into the environment, it would be easily converted to methylmercury by aquatic microorganisms, which can cause severe damage to endocrine system, kidneys, skin and DNA by accumulating in the human body through the food chain. [1] Considering these environmental and health hazards associated with Hg 2+ , it is important to develop artificial receptors with high selectivity and sensitivity for Hg 2+ both in the environment and biological systems. [2] In recent years, a number of fluorescent probes for selective detection of Hg 2+ have been developed.…”

“…1 H NMR (400 MHz) titration spectra of probe 1 (3.75 mM) in CD 3 CN solvent upon addition of mercury(II) perchlorate hydrate aqueous solution in D 2 O.…”