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See Supporting Information for characterisation data for alcohols 12 and 13 and for NOE data.
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3·THF present at the start of the reaction. It was necessary to add aliquots of the catalyst periodically to achieve the desired conversion, which could be monitored by GC of the crude product (Agilent 6890N GC, Varian Chirasil Dex-CB column (25 m × 0.25 mm) using Helium as the carrier gas, 25 psi, 19:1 split, 100°C, retention times: 26.5 min (10), 24.5 min (11)).
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3·THF present at the start of the reaction. It was necessary to add aliquots of the catalyst periodically to achieve the desired conversion, which could be monitored by GC of the crude product (Agilent 6890N GC, Varian Chirasil Dex-CB column (25 m × 0.25 mm) using Helium as the carrier gas, 25 psi, 19:1 split, 100°C, retention times: 26.5 min (10), 24.5 min (11)).
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See Supporting Information for further details of the coupling constant calculations for major and minor cycloadducts
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See Supporting Information for further details of the coupling constant calculations for major and minor cycloadducts.
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Mosher's esters of 19 were prepared, which showed that no epimerisation had occurred at the CIO centre during deprotection of the BDA group. See Supporting Information for full procedures and characterisation.
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For the syn-reduction different batches gave variable yields and diastereoselectivities. It is believed that molybdenum salts residual from the previous reaction enhanced the diastereoselectivity (the hydroxyketone starting material showed levels of a pink colouration that varied from batch to batch which could be ascribed to residual metal contamination).
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Hydrolysis under conditions similar to those used by Molinski (see ref. [15]) for the corresponding ethyl acetal but 10 equivalents of water were required. The aldehyde product is volatile and care is needed when handling under reduced pressure.
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Hydrolysis under conditions similar to those used by Molinski (see ref. [15]) for the corresponding ethyl acetal but 10 equivalents of water were required. The aldehyde product is volatile and care is needed when handling under reduced pressure.
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See Supporting Information for selected results of the catalyst screen.
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95
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34547486626
-
-
For cyanohydrin 41 and α-hydroxyester 42, the ee was assessed by formation of the Mosher's esters. See Supporting Information for experimental procedures and full characterisation of the Mosher's esters.
-
For cyanohydrin 41 and α-hydroxyester 42, the ee was assessed by formation of the Mosher's esters. See Supporting Information for experimental procedures and full characterisation of the Mosher's esters.
-
-
-
-
96
-
-
34547420360
-
-
Unfortunately, attempts to scale up the enantioselective addition of TMSCN caused a significant decrease of the ee value (10 mmol: 52% ee, 70% yield). Any attempt to enrich the ee of the cyanohydrin by recrystallisation returned material with the same ee (cold PE/ethyl acetate 4:1) or completely destroyed the ee (13% ee, from hot cydohexane/ethyl acetate 4:1).
-
Unfortunately, attempts to scale up the enantioselective addition of TMSCN caused a significant decrease of the ee value (10 mmol: 52% ee, 70% yield). Any attempt to enrich the ee of the cyanohydrin by recrystallisation returned material with the same ee (cold PE/ethyl acetate 4:1) or completely destroyed the ee (13% ee, from hot cydohexane/ethyl acetate 4:1).
-
-
-
-
97
-
-
34547433294
-
-
The corresponding bromide analogue of 46 is reported to be very unstable, see references [45] and [48].
-
The corresponding bromide analogue of 46 is reported to be very unstable, see references [45] and [48].
-
-
-
-
98
-
-
0001022734
-
-
B.-C. Chen, C. K. Murphy, A. Kumar, R. T. Reddy, C. Clark, P. Zhou, B. M. Lewis, D. Sala, I. Mergelsberg, D. Scherer, J. Buckley, D. DiBenedetto, F. A. Davis, Org. Synth. 1996, 72, 159.
-
(1996)
Org. Synth
, vol.72
, pp. 159
-
-
Chen, B.-C.1
Murphy, C.K.2
Kumar, A.3
Reddy, R.T.4
Clark, C.5
Zhou, P.6
Lewis, B.M.7
Sala, D.8
Mergelsberg, I.9
Scherer, D.10
Buckley, J.11
DiBenedetto, D.12
Davis, F.A.13
-
99
-
-
34547460800
-
-
Using the, -oxaziridines the unnatural (R)-configured α-hydroxy ester was formed preferentially
-
Using the (+)-oxaziridines the unnatural (R)-configured α-hydroxy ester was formed preferentially.
-
-
-
-
100
-
-
0036313620
-
-
G. Hanquet, X. J. Salom-Roig, S. Lemeitour, G. Solladié, Eur. J. Org. Chem. 2002, 2112.
-
(2002)
Eur. J. Org. Chem
, pp. 2112
-
-
Hanquet, G.1
Salom-Roig, X.J.2
Lemeitour, S.3
Solladié, G.4
-
101
-
-
34547459735
-
-
Attempts to form the CIO stereochemistry by an enantioselective reduction of the α-ketoester formed by the oxidation of rac-48 gave low yields and ee. See Supporting Information for characterisation of the ketone intermediate
-
Attempts to form the CIO stereochemistry by an enantioselective reduction of the α-ketoester formed by the oxidation of rac-48 gave low yields and ee. See Supporting Information for characterisation of the ketone intermediate.
-
-
-
-
103
-
-
19544377371
-
-
b) A. Sakakura, R. Kondo, K. Ishihara, Org. Lett. 2005, 7, 1971.
-
(2005)
Org. Lett
, vol.7
, pp. 1971
-
-
Sakakura, A.1
Kondo, R.2
Ishihara, K.3
-
104
-
-
34547460799
-
-
The ee value for 51, 52, and 62 was determined using HPLC on a chiral stationary phase (see Experimental Section for further details). Both CIO epimers (from amides 25 and 44) were progressed through the same steps to aid determination of retention times for the enantiomers.
-
The ee value for 51, 52, and 62 was determined using HPLC on a chiral stationary phase (see Experimental Section for further details). Both CIO epimers (from amides 25 and 44) were progressed through the same steps to aid determination of retention times for the enantiomers.
-
-
-
-
105
-
-
0037588850
-
-
N. Endoh, K. Tsuboi, R. Kim, Y. Yonezawa, C.-G. Shin, Heterocydes 2003, 60, 1567.
-
(2003)
Heterocydes
, vol.60
, pp. 1567
-
-
Endoh, N.1
Tsuboi, K.2
Kim, R.3
Yonezawa, Y.4
Shin, C.-G.5
-
106
-
-
34547432762
-
-
These studies were performed with the enantiomer of enamide 52, ent-52.
-
These studies were performed with the enantiomer of enamide 52, ent-52.
-
-
-
-
107
-
-
34547454442
-
-
Treatment of enamide ent-52 with NBS, and benzyl alcohol formed the desired bromide 56, however, benzyl alcohol ran very close to the desired product by TLC and was problematic to remove. The use of fewer equivalents of the nucleophile resulted in a poor yield of 56 as shown and alcohol 57 was also isolated in 37 % following an aqueous quench.
-
Treatment of enamide ent-52 with NBS, and benzyl alcohol formed the desired bromide 56, however, benzyl alcohol ran very close to the desired product by TLC and was problematic to remove. The use of fewer equivalents of the nucleophile resulted in a poor yield of 56 as shown and alcohol 57 was also isolated in 37 % following an aqueous quench.
-
-
-
-
110
-
-
34547460252
-
-
The ee value was determined by supercritical fluid chromatography on a chiral stationary phase following conversion into the primary alcohol 63 (see Experimental Section for further details).
-
The ee value was determined by supercritical fluid chromatography on a chiral stationary phase following conversion into the primary alcohol 63 (see Experimental Section for further details).
-
-
-
-
111
-
-
34547479470
-
-
Oxime 33 was isolated as a mixture of double bond isomers and the cis/trans ratio depended on the oxidation method. TPAP oxidation gave predominantly cis-oxime (up to 5:1 cis/trans) presumably due to chelation with residual ruthenium salts promoting a cis-conformation, whereas following DMP oxidation the trans-oxime was favoured (up to 1:5 cis/trans, The mixture geometries made the assessment of enantiopurity by chiral HPLC very difficult so a number of batches of bisoxazole 62 (with a range of enantiopurities) were progressed to the oxime and the optical rotation values were recorded. Pleasingly, the different batches gave reproducible and consistent αD values suggesting the stereochemical integrity had been maintained. This was confirmed following the cycloaddition, from which none of the C10 epimer was observed
-
D values suggesting the stereochemical integrity had been maintained. This was confirmed following the cycloaddition, from which none of the C10 epimer was observed.
-
-
-
-
112
-
-
34547417756
-
-
See Supporting Information for selected results in the optimisation of the nitrile oxide cycloaddition between alkene 7 and the nitrile oxide derived from oxime 33
-
See Supporting Information for selected results in the optimisation of the nitrile oxide cycloaddition between alkene 7 and the nitrile oxide derived from oxime 33.
-
-
-
-
113
-
-
34547452919
-
-
The nitrile oxide dimer was also isolated in only 6 %. Excess alkene employed in the reaction was recovered in excellent yields. See Supporting Information for characterisation data for minor cycloadduct diastereomer 3a and nitrile oxide dimer 3b.
-
The nitrile oxide dimer was also isolated in only 6 %. Excess alkene employed in the reaction was recovered in excellent yields. See Supporting Information for characterisation data for minor cycloadduct diastereomer 3a and nitrile oxide dimer 3b.
-
-
-
-
114
-
-
5144232470
-
-
a) S. H. Jung, J. E. Lee, H. Y. Koh, Bull. Korean Chem. Soc. 1998, 19, 33;
-
(1998)
Bull. Korean Chem. Soc
, vol.19
, pp. 33
-
-
Jung, S.H.1
Lee, J.E.2
Koh, H.Y.3
-
117
-
-
0001249486
-
-
K.-M. Chen, G. E. Hardtmann, K. Prasad, O. Repic, M. J. Shapiro, Tetrahedron Lett. 1987, 28, 155.
-
(1987)
Tetrahedron Lett
, vol.28
, pp. 155
-
-
Chen, K.-M.1
Hardtmann, G.E.2
Prasad, K.3
Repic, O.4
Shapiro, M.J.5
-
118
-
-
34547424029
-
-
See Supporting Information for characterisation of the minor cycloadduct isoxazoline 69 a. The diastereoselectivity was consistently lower in the 10-epi-series (ent-33) than with oxime 33 (dr 2.5:1 vs 3.5:1). Notwithstanding the distance of the chirality from the reacting centre, this was presumed to be due to a chirality match/mismatch between alkene 7 and the chiral oximes. A similar phenomenon was observed for the enantiomer of the nitrile oxide of Garner's aldehyde oxime (dr 4.1:1 vs 2.5:1) although in this case the chirality is closer to the reacting centres.
-
See Supporting Information for characterisation of the minor cycloadduct isoxazoline 69 a. The diastereoselectivity was consistently lower in the 10-epi-series (ent-33) than with oxime 33 (dr 2.5:1 vs 3.5:1). Notwithstanding the distance of the chirality from the reacting centre, this was presumed to be due to a chirality match/mismatch between alkene 7 and the chiral oximes. A similar phenomenon was observed for the enantiomer of the nitrile oxide of Garner's aldehyde oxime (dr 4.1:1 vs 2.5:1) although in this case the chirality is closer to the reacting centres.
-
-
-
-
119
-
-
34547421411
-
-
See Supporting Information for spectra for bengazole A, 10-epi-bengazole A and bengazole B
-
See Supporting Information for spectra for bengazole A, 10-epi-bengazole A and bengazole B.
-
-
-
-
120
-
-
0001915209
-
-
a) H. Takikawa, D. Nozawa, A. Kayo, S. Muto, K. Mori, J. Chem. Soc. Perkin Trans. 1 1999, 2467;
-
(1999)
J. Chem. Soc. Perkin Trans. 1
, pp. 2467
-
-
Takikawa, H.1
Nozawa, D.2
Kayo, A.3
Muto, S.4
Mori, K.5
-
121
-
-
0032542155
-
-
b) T. Shioiri, Y. Terao, N. Irako, T. Aoyama, Tetrahedron 1998, 54, 15 701.
-
(1998)
Tetrahedron
, vol.54
, pp. 15-701
-
-
Shioiri, T.1
Terao, Y.2
Irako, N.3
Aoyama, T.4
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