S. J. Meek et al. / Tetrahedron Letters 48 (2007) 4165–4168
4167
In conclusion, we have found that enantioenriched pyr-
anyl enol ethers undergo rearrangement to provide the
corresponding cyclohexanones in high yield and good
enantiocontrol. In contrast, the isomeric dihydropyrans
appear to be subject to faster racemisation processes
resulting in racemic cyclobutane products.
X
O
3.0 eq Et2AlCl
DCM, -78 oC
O
Me3Si
X
Co2(CO)6
SiMe3
(OC)6Co2
X=CH2; 13
X=NTs; 14
16; 83%, 87% ee
17; 51%; 74% ee
Acknowledgements
Scheme 5.
We thank the EPSRC and GSK for studentship
funding.
strates proceeded smoothly, allowing the corresponding
products to be generated in good yields and enantio-
selectivities (Scheme 5).13
References and notes
Finally, we wanted to extend these studies to include an
enantioselective cyclobutane formation by a Co-medi-
ated ring contraction process.2e,f Accordingly, dihydro-
pyran complexes 18 and 19 were prepared from
phosphonium salt 10 by a three-step sequence (Scheme
6).
1. Meek, S. J.; Harrity, J. P. A. Tetrahedron 2007, 63, 3081.
2. (a) Carbery, D. R.; Reignier, S.; Myatt, J. W.; Miller, N.
D.; Harrity, J. P. A. Angew. Chem., Int. Ed. 2002, 41, 2584;
(b) Carbery, D. R.; Miller, N. D.; Harrity, J. P. A. Chem.
Commun. 2002, 1546; (c) Carbery, D. R.; Reignier, S.;
Miller, N. D.; Adams, H.; Harrity, J. P. A. J. Org. Chem.
2003, 68, 4392; (d) Meek, S. J.; Pradaux, F.; Carbery, D.
R.; Demont, E. H.; Harrity, J. P. A. J. Org. Chem. 2005,
70, 10046; (e) Meek, S. J.; Pradaux, F.; Demont, E. H.;
Harrity, J. P. A. Org. Lett. 2006, 8, 5597; (f) Meek, S. J.;
Pradaux, F.; Demont, E. H.; Harrity, J. P. A. J. Org.
Chem. 2007, 72, 3467.
Considering the results obtained in Table 1 and Scheme 5,
we were hopeful that useful levels of enantiomeric purity
would be retained in this process. In the event however,
the rearrangement provided racemic material in both
cases (Scheme 7).14 We speculate that the reasons for
the poor enantiocontrol in the ring contraction reactions
to cyclobutanes is due to the relative sluggishness of
4-membered ring formation via cyclisation processes.15
Indeed, this is manifested somewhat in the requirement
for these reactions to be performed at elevated temper-
atures (ꢀ78 to ꢀ30 °C) relative to the cyclohexanone
forming reactions described earlier.
3. For the employment of this strategy in the synthesis of
difluorocarbasugars see: Deleuze, A.; Menozzi, C.; Sollo-
goub, M.; Sinay, P. Angew. Chem., Int. Ed. 2004, 43, 6680.
¨
4. For recent reviews see: (a) Nicholas, K. M. Acc. Chem.
Res. 1987, 20, 207; (b) Caffyn, A. J. M.; Nicholas, K. M.
In Comprehensive Organometallic Chemistry II; Abel, E.
W., Stone, F. G. A., Wilkinson, G., Hegedus, L. S., Eds.;
Pergamon: Oxford, 1995; Vol. 12, p 685; (c) Green, J. R.
Curr. Org. Chem. 2001, 5, 809; (d) Teobald, B. J.
Tetrahedron 2002, 58, 4133.
5. Schreiber, S. L.; Klimas, M. T.; Sammakia, T. J. Am.
Chem. Soc. 1987, 109, 5749.
6. For density functional calculations of Nicholas carboca-
tions see: Pfletschinger, A.; Koch, W.; Schmalz, H.-G.
Chem. Eur. J. 2001, 7, 5325.
1. n-BuLi, THF, -78 oC, PhCHO
Ph
2. 5 mol% PPTS, C6H6, reflux
O
3. Co2(CO)8, DCM, rt
10
Me3Si
Co2(CO)6
7. Muehldorf, A. V.; Guzman-Perez, A.; Kluge, A. F.
Tetrahedron Lett. 1994, 35, 8755.
18; 22%
8. An isolated example of an enantioselective Ti-promoted
rearrangement has been reported from these laborato-
ries.2c Subsequent studies however have shown Al-medi-
ated rearrangements to be generally more efficient.2d
9. Pattenden, L. C.; Wybrow, R. A. J.; Smith, S. A.; Harrity,
J. P. A. Org. Lett. 2006, 8, 3089.
1. n-BuLi, THF, -78 oC, tBuCHO
2. Co2(CO)8, DCM, rt
But
O
10
3. 5 mol% PPTS, DCM, rt
Me3Si
Co2(CO)6
19; 56%
10. Buchi Grignard reagents have been documented to add to
¨
epoxides to prepare pyrans: (a) Street, S. D. A.; Yeates, C.;
Kocienski, P.; Campbell, S. F. Chem. Commun. 1985,
1386; (b) Rainier, J. D.; Allwein, S. P. Tetrahedron Lett.
1998, 39, 9601; (c) Allwein, S. P.; Cox, J. M.; Howard, B.
E.; Johnson, H. W. B.; Rainier, J. D. Tetrahedron 2002,
58, 1997.
Scheme 6.
O
R
3.0 eq Et2AlCl
DCM
11. Chiral HPLC analysis carried out on a Chiralpak OD
column, 95:5 hexane/isopropanol, 1 mL/min; tR(mi-
nor) = 21.75 min, tR(major) = 23.92 min. Unfortunately,
we were unable to separate the enantiomers of trans-11,
and have therefore assumed cis-11 to provide an adequate
assay of enantiopurity at the propargylic stereocentre.
12. Substrate E-12 gave rise to the cis-isomer of cyclohexa-
none 15, this compound was isomerised to the corre-
sponding trans-isomer (silica gel chromatography: petrol/
R
O
Co2(CO)6
-78 to -30 oC
Me3Si
Co2(CO)6
SiMe3
20; 81%, 0% ee
21; 54%; 0% ee
R=Ph; 18
X=tBu; 19
Scheme 7.