Chiral synthesis via organoboranes. 7. Diastereoselective and enantioselective synthesis of erythro- and threo-.beta.-methylhomoallyl alcohols via enantiomeric (Z)- and (E)-crotylboranes

Brown, Herbert C.; Bhat, K. S.

doi:10.1021/ja00279a042

Cited by 367 publications

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“…Brown crotylation [10] of 9 produced the allylic alcohol 10, but a Sharpless kinetic resolution [11] step had to be included for improvement of the enantiomeric purity. For preparation of the final Scheme 1.…”

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confidence: 99%

Total Synthesis of (+)‐Exiguolide

Kwon

Woo

et al. 2008

Angew Chem Int Ed

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Exiguolide (1) is a unique 16-membered macrolide isolated from the marine sponge Geodia exigua Thiele (order Astrophorida, family Geodiidae).[1] It specifically inhibits fertilization of sea urchin (Hemicentrotus pulcherrimus) gametes but not embryogenesis of the fertilized egg. The macrolide structure incorporates two cis-2,6-disubstituted oxane rings, one of which carries an exocyclic enoate appendage reminiscent of bryostatins. The unique structural features and interesting biological activity of 1 has generated considerable interest in this compound, and herein we report our recent results for the total synthesis of 1.Scheme 1 shows the retrosynthetic analysis of 1. Thus, the target would be synthesized through a ring-closing olefin metathesis reaction of the carboxylate ester A followed by construction of the triene side chain. Fragments B and C are the constituents of the ester A. Fragment B may be obtained from Prins cyclization [2] of the b-alkoxyacrylate D, which should be accessible from the oxane derivative E. Fragment E may in turn be obtained by radical cyclization [3] of the b-alkoxyacrylate F.For synthesis of the B fragment, the secondary alcohol 3 was prepared from the known aldehyde 2[4] through Brown allylation, [5] hydroboration-oxidation, and protection of the primary hydroxy group with TBS (Scheme 2). The reaction of 3 with methyl propiolate in the presence of N-methylmorpholine produced the corresponding b-alkoxyacrylate derivative, which was converted into the iodide 4 by cleavage of the TBS group and iodide substitution. Radical cyclization [3] of 4 in the presence of 1-ethylpiperidinium hypophosphite and triethylborane in ethanol [6] proceeded efficiently and selectively to yield, almost quantitatively, the oxane 5. DIBAL reduction of 5 and a second Brown allylation led to a homoallylic secondary alcohol product, from which a second b-alkoxyacrylate derivative 6 was obtained by reaction with methyl propiolate. In the presence of trifluoroacetic acid, Prins cyclization [2] of 6 was successful and the products were hydrolyzed to a mixture ( % 3:1) of alcohols, which was then converted into the ketone derivative 7 by Dess-Martin oxidation. There were signs of partial ( % 7:1) racemization [7] in the Prins cyclization step. The keto ester 7 was converted into the keto acid 8 by dimethyl ketalization-hydrogenolysis, Dess-Martin oxidation, and rhodium-catalyzed methylenation [8] of the product aldehyde, followed by hydrolysisdeketalization and subsequent chromatographic separation.The known aldehyde 9 [9] served as the starting material in the synthesis of the C fragment (Scheme 3). Brown crotylation [10] of 9 produced the allylic alcohol 10, but a Sharpless kinetic resolution [11] step had to be included for improvement of the enantiomeric purity. For preparation of the final Scheme 1. Retrosynthetic analysis of exiguolide (1).

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confidence: 99%

Total Synthesis of (+)‐Exiguolide

Kwon

Woo

et al. 2008

Angew Chem Int Ed

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“…Syn-homoallyl alcohol 120 was synthesised in >95% ee by reaction of the chiral (Z)-crotyl borane 121 [51] with isobutyraldehyde followed by oxidative workup (Scheme 24). The terminal vinyl group of 120 was subjected to ozonolytic cleavage and subsequent HornerEmmons olefination gave the α,β-unsaturated ester 85.…”

Section: Ghosh's Synthesis Of Madumycin IImentioning

confidence: 99%

Chemistry and Biology of the Streptogramin A Antibiotics

Ahmed¹,

Donaldson²

2007

MROC

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“…[18a, 31] In the cases of the crotylboration, there are eight possible transition states, four of which will be predominant, depending on the geometry of the isopinocampheyl group and the butene used. [32] Comparing the optical rotation values of the obtained amine 2 a with those report- ee [%] [b] 1 7 a Ph À100 2 a 90 (87) [c] 88 (94) [c] [c] 81 (81) [c] 3 7 c 4-MeO-(C 6 H 4 ) À100 2 c 89 (74) [c] 91 (92) [c] [d] [a] All yields are of pure isolated products. [b] Enantiomeric excess was determined with HPLC using Chiracel OD-H column and hexanes/isopropanol as the mobile phase.…”

Section: Alkoxyallylboration Of N-silylimines: Alkoxyallylboration Ofmentioning

confidence: 99%

Highly Diastereoselective and Enantioselective Preparation of Homoallylic Amines: Application for the Synthesis of β‐Amino Acids and γ‐Lactams

Ramachandran

Burghardt

2005

Chemistry A European J

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Reactions of N-silyl- and N-aluminoimines with B-allyldiisopinocampheylborane in the presence of methanol, followed by oxidative workup furnished homoallylic amines in good yields and high ee. A 11B NMR spectroscopy study revealed that the reactions do not proceed, even at room temperature, unless a molar equivalent of water or methanol is added. The first reagent-controlled asymmetric crotylboration and alkoxyallylboration of aldimines furnishing beta-methyl or beta-alkoxy homoallylic amines in very high diastereoselectivity and enantioselectivity are reported herein. Crotylboration and alkoxyallylboration of imines proceed only with the "allyl"-boron "ate" complexes, instead of the "allyl"-dialkylboron reagents used with aldehydes. The addition of methanol is necessary for these reactions as well. Application of this methodology for the conversion of representative nitriles to beta-amino acids in two steps has been described. Additionally, a procedure for the preparation of chiral delta-amino alcohols and gamma-lactams from nitriles is also reported.

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Chiral synthesis via organoboranes. 7. Diastereoselective and enantioselective synthesis of erythro- and threo-.beta.-methylhomoallyl alcohols via enantiomeric (Z)- and (E)-crotylboranes

Cited by 367 publications

References 0 publications

Total Synthesis of (+)‐Exiguolide

Total Synthesis of (+)‐Exiguolide

Chemistry and Biology of the Streptogramin A Antibiotics

Highly Diastereoselective and Enantioselective Preparation of Homoallylic Amines: Application for the Synthesis of β‐Amino Acids and γ‐Lactams

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