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DOI: 10.1055/s-0029-1217374
Glyceraldehyde Acetonide - Recent Applications of this Chiron in Organic Synthesis
Publikationsverlauf
Publikationsdatum:
16. Juni 2009 (online)
Biographical Sketches
![](https://www.thieme-connect.de/media/synlett/200911/v290_lima.jpg)
Introduction
Glyceraldehyde acetonide (2,3-O-isopropylidene-d-glyceraldehyde, 1) it is a well-known chiron which has been used in organic synthesis for multiple purposes. [¹] It has been applied on the synthesis of a β-adrenergic antagonist, [²] on multicomponent reaction in the synthesis of nakadomarin A precursor, [³] and reacts with several organometallics to afford chiral alcohols used as precursors in total syntheses. [4-7] Its R isomer is easily prepared from selective protection and oxidative cleavage of inexpensive and available commercially d-mannitol (Scheme [¹] ) [8] and its enantiomer can be obtained from vitamin C. [9] The present Spotlight emphasises recent applications of this chiron in organic synthesis in its R and S enantiomeric forms.
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Scheme 1
Abstracts
(A) Ahrendt and Williams reported the synthesis of the ADE fragment of nakadomarin A by a stereoselective three-component 1,3-dipolar cycloaddition with azomethine ylide obtained from 1. The formation of the 2,5-trans-cycloadduct resulted in a single diastereomer. [³] |
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(B) The construction of C1-C21 linear skeleton of tartrolon B was reported by Kim and Lee. The synthesis started with the asymmetric crotylation of aldehyde 1 to yield the syn-crotyl adduct. [¹0] |
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(C) Wang’s group synthesized the β-adrenergic antagonist (S,R,R,R)-nebivolol using the pyrrolidine-catalyzed cyclization between 1 and 2-acetyl-4-fluorophenol. This key step gave a diastereomeric mixture of products (S,R)/(R,R) (60:40) in 40% yield, which could be easily separated by chromatography. Both isomers were used to prepare (S,R,R,R)-nebivolol. [²] |
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(D) Both enantiomers of 1 were used by Casiraghi’s group to prepare amino acids polyols via a vinylogous Mukaiyama aldol reaction, standard protection of the resulting alcohol as a TMS ether, and a variant of the Morita-Baylis-Hillman reaction using a pyrrole as starting material and exploiting the configuration of 1. [¹¹] |
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(E) Treatment of a prochiral symmetrical ketone 2 with chiral lithium amides leads to the formation of non-racemic lithium enolates. The base discriminates between two enantiotopic protons H R and H S and the resulting enolate could be trapped with electrophiles as 1, exhibiting a double stereoselection. [¹²] |
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(F) Diethylaminosulfur trifluoride (DAST) was used on fluorination of (S)-1 for the preparation of difluorated ketal 4 used to prepare b-difluoroalanine and g-difluorothreonine as useful building blocks for the preparation of biologically active peptides and peptidomimetics. [¹³] |
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(G) Kumaraswamy and Markondaiah synthesized stereoselectively the natural and unnatural nocardiolactone using 1 as starting material. [¹4] They indicated the synthesis accomplishing a (S)-proline-catalyzed crossed aldol reaction between eicosanal and aldehyde 1. They changed (S)- to (R)-proline under otherwise identical conditions, but the results indicated that there is a negligible matched or mismatched effect on the diastereoselectivity of the product. |
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(H) Shibasaki’s group related the stereodivergent construction of three contiguous stereocenters in catalytic doubly diastereoselective nitroaldol reactions of α-chiral aldehydes with nitroacetaldehyde dimethyl acetal using heterobimetallic catalysts. [¹5] (S)-LLB was employed as catalyst to prepare nitroadduct 5 from 1 in good yields and diastereoselectivity. |
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- For a review, see:
- 1
Jurczak J.Pikul S.Bauer T. Tetrahedron 1986, 42: 447 - 2
Wang N.-X.Yu A.-G.Wang G.-X.Zhang X.-H.Li Q.-S.Li Z. Synthesis 2007, 1154 - 3
Ahrendt KA.Williams RM. Org. Lett. 2004, 6: 4539 - 4
Fettes A.Carreira EM. J. Org. Chem. 2003, 68: 9274 - 5
Cossy J.Willis C.Bellosta V.BouzBouz S. J. Org. Chem. 2002, 67: 1982 - 6
Guaragna A.Napolitano C.D D.Alonzo Pedatella S.Palumbo G. Org. Lett. 2006, 8: 4863 - 7
Huckins JR.Vicente J.Rychnovsky SD. Org. Lett. 2007, 9: 4757 -
8a
Earle MJ.Abdur-Rashid A.Priestley ND. J. Org. Chem. 1996, 61: 5697 -
8b
Schmid CR.Bryant JD.Dowlatzedah M.Phillips JL.Prather DE.Schantz RD.Sear NL.Vianco CS. J. Org. Chem. 1991, 56: 4056 -
9a
Hubschwerlin C. Synthesis 1986, 962 -
9b
Mikkilineni AB.Kumar P.Abushanab E. J. Org. Chem. 1988, 53: 6005 - 10
Kim YJ.Lee D. Org. Lett. 2006, 8: 5219 - 11
Curti C.Zanardi F.Battistini L.Sartori A.Rassu G.Auzzas L.Roggio A.Pinna L.Casiraghi G. J. Org. Chem. 2006, 71: 225 - 12
Majewski M.Nowak P. J. Org. Chem. 2000, 65: 5152 - 13
Li G.van der Donk WA. Org. Lett. 2007, 9: 41 - 14
Kumaraswamy G.Markondaiah B. Tetrahedron 2008, 64: 5861 - 15
Sohtome Y.Kato Y.Handa S.Aoyama N.Nagawa K.Matsunaga S.Shibasaki M. Org. Lett. 2008, 10: 2231
References
- For a review, see:
- 1
Jurczak J.Pikul S.Bauer T. Tetrahedron 1986, 42: 447 - 2
Wang N.-X.Yu A.-G.Wang G.-X.Zhang X.-H.Li Q.-S.Li Z. Synthesis 2007, 1154 - 3
Ahrendt KA.Williams RM. Org. Lett. 2004, 6: 4539 - 4
Fettes A.Carreira EM. J. Org. Chem. 2003, 68: 9274 - 5
Cossy J.Willis C.Bellosta V.BouzBouz S. J. Org. Chem. 2002, 67: 1982 - 6
Guaragna A.Napolitano C.D D.Alonzo Pedatella S.Palumbo G. Org. Lett. 2006, 8: 4863 - 7
Huckins JR.Vicente J.Rychnovsky SD. Org. Lett. 2007, 9: 4757 -
8a
Earle MJ.Abdur-Rashid A.Priestley ND. J. Org. Chem. 1996, 61: 5697 -
8b
Schmid CR.Bryant JD.Dowlatzedah M.Phillips JL.Prather DE.Schantz RD.Sear NL.Vianco CS. J. Org. Chem. 1991, 56: 4056 -
9a
Hubschwerlin C. Synthesis 1986, 962 -
9b
Mikkilineni AB.Kumar P.Abushanab E. J. Org. Chem. 1988, 53: 6005 - 10
Kim YJ.Lee D. Org. Lett. 2006, 8: 5219 - 11
Curti C.Zanardi F.Battistini L.Sartori A.Rassu G.Auzzas L.Roggio A.Pinna L.Casiraghi G. J. Org. Chem. 2006, 71: 225 - 12
Majewski M.Nowak P. J. Org. Chem. 2000, 65: 5152 - 13
Li G.van der Donk WA. Org. Lett. 2007, 9: 41 - 14
Kumaraswamy G.Markondaiah B. Tetrahedron 2008, 64: 5861 - 15
Sohtome Y.Kato Y.Handa S.Aoyama N.Nagawa K.Matsunaga S.Shibasaki M. Org. Lett. 2008, 10: 2231
References
![](https://www.thieme-connect.de/media/synlett/200911/v290_s1.gif)
Scheme 1
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