C O M M U N I C A T I O N S
developed. A sizable number of suitable nucleophiles were dis-
covered to be efficacious for this sequential reaction including, but
certainly not limited to, alkyl metal species, silyl enol ethers, as
well as dienes for the hetero Diels-Alder reaction. The important
factors for the described reactions are: (1) extremely low catalyst
loading for the initial aldol allows for acidic or basic reagents to
be sequentially added without erosion of yields or selectiVities, and
(2) super silyl allows for extremely high diastereoselection in the
initial aldol as well as the following sequential reaction, generating
multiple stereocenters in one pot. We believe this is an important
method for efficiently generating polyol-containing compounds with
very high selectivity and high yield. Furthermore, we have
demonstrated the power of one-pot procedures for generating
multifunctional compounds stereoselectively. Further applications
utilizing the super silyl group are currently underway.
Figure 1. Van der Waals volume vs number of atoms of typical silyl
protecting groups.
Scheme 2. Three-Step Synthesis of (+)Cryptocarya Diacetate
Acknowledgment. Thanks to Novartis Pharmaceuticals (ACS,
Division of Organic Chemistry Fellowship) for funding. Thanks
to Ian Steele for X-ray analysis and Antoni Jurkiewicz for NMR
expertise. Also, thanks to Stefan Kilyanek for helpful discussions.
Supporting Information Available: Experimental procedures,
compound characterization; crystallographic data in CIF format. This
References
ored on the extremely concise synthesis of cryptocarya diacetate.
This compound has been isolated from the bark of the South African
plant, Cryptocarya latifolia, which has been used for medicinal
purposes.12 The aldol reaction was performed under standard
conditions with 0.05 mol % HNTf2; subsequent addition of 1.2
equiv of allyl magnesium bromide followed by acryloyl chloride
provided dienyl compound 3 in 63% yield along with a 24% yield
of an inseparable mixture of the other minor diastereomers (Scheme
2). Use of Grubb’s second generation catalyst for ring-closing
metathesis gave 4, which was treated with HF/pyridine followed
by addition of excess pyridine and acetic anhydride to give
cryptocarya diacetate in 57% yield with a 32% overall yield for
the three steps.
We attribute the high diastereoselectivity obtained by using super
silyl-containing substrates and catalysts partly due to the steric
influence of the group.13 Along these lines, the van der Waals
volumes of common silyl groups were calculated for the parent
silanes (R3SiH) using the method of Abraham (Figure 1, front
row).14 The volumes were also normalized by dividing by the
number of atoms in the molecule to gain insight into how the steric
size relates to atom economy (Figure 1, back row). To this point,
TBS and pentamethyldisilane (PMDS) have the same number of
atoms, but have the third lowest and second highest ratio,
respectively, pointing to the value of having Si-Si bonds present
to increase size without decreasing atom economy. The super silyl
group having three Si-Si bonds has the highest van der Waals
volume as well as the highest ratio, highlighting its overwhelming
steric influence created by the Si-Si bonds. Interestingly, the TIPS
group, which has the second highest van der Waals volume, has
the worst volume-to-number of atoms ratio.
(1) (a) Rychnovsky, S. D. Chem. ReV. 1995, 95, 2021. (b) Koskinen, A. M.
P.; Karisalmi, K. Chem. Soc. ReV. 2005, 34, 677.
(2) Recent examples of one-pot synthesis of stereodefined polyol com-
pounds: (a) Wang, X.; Meng, Q.; Perl, N. R.; Xu, Y.; Leighton, J. L. J.
Am. Chem. Soc. 2005, 127, 12806. (b) Northrup, A. B.; MacMillan, D.
W. C. Science 2004, 305, 1753. (c) Zacuto, M. J.; O’Malley, S. L.;
Leighton, J. L. Tetrahedron 2003, 59, 8889. (d) Wang, X.; Meng, Q.;
Nation, A. J.; Leighton. J. L. J. Am. Chem. Soc. 2002, 124, 10672.
(3) (a) Boxer, M. B.; Yamamoto, H. Org. Lett. 2005, 7, 3127. (b) Boxer, M.
B.; Yamamoto, H. J. Am. Chem. Soc. 2006, 128, 48.
(4) A highly detailed synthesis of the acetaldehyde super silyl enol ether and
its large-scale aldol reaction with pivalaldehyde has been described: Boxer,
M. B.; Yamamoto, H. Nature Protocols 2006, 1, 2434.
(5) A term coined by Hans Bock: Bock, H.; Meuret, J.; Ruppert, K. Angew.
Chem., Int. Ed. Engl. 1993, 32, 414.
(6) Hall, N. Science 1994, 266, 32.
(7) For sequential and tandem reactions: (a) Ho, T.-L. Tandem Organic
Reactions; Wiley: New York, 1992. (b) Tietze, L. F.; Beifuss, U. Angew.
Chem., Int. Ed. Engl. 1993, 32, 131.
(8) For acid/base combined systems, see: (a) Gelman, F.; Blum, J.; Avnir,
D. J. Am. Chem. Soc. 2000, 122, 11999. (b) Motokura, K.; Fujita, N.;
Mori, K.; Mizugaki, T.; Ebitani, K.; Kaneda, K. J. Am. Chem. Soc. 2006,
127, 9674 and references therein.
(9) Determined syn via acetonide method of Rychnovsky: Rychnovsky, S.
D.; Rogers, B.; Yang, G. J. Org. Chem. 1993, 58, 3511.
(10) Kozmin, S. A.; Rawal, V. H. J. Org. Chem. 1997, 62, 5252.
(11) The initial aldol reaction proceeds in 91% yield with 77/23 syn/anti
selectivity. See Supporting Information for details. This is different from
typical â-oxygenated aldehydes (see: Evans, D. A.; Cee, V. J.; Siska, S.
J. Tetrahedron Lett. 1994, 35, 8537), but we believe differences arise
from the combination of bulky super silyl-enol ether and -cation, which
greatly differ from substrates and catalysts in the reference.
(12) Isolation: Drewes, S. E.; Sehlapelo, B. M.; Horn, M. M.; Scott-Shaw,
R.; Sandor, P. Phytochemistry 1995, 38, 1427. Synthesis: (a) Jørgensen,
K. B.; Suenaga, T.; Nakata, T. Tetrahedron Lett. 1999, 40, 8855. (b)
Hunter, T. J.; O’Doherty, G. A. Org. Lett. 2001, 3, 2777. (c) Smith, G.
M.; O’Doherty, G. A. Org. Lett. 2003, 5, 1959. (d) Krishna, P. R.; Reddy,
V. V. R. Tetrahedron Lett. 2005, 46, 3905.
(13) For calculations comparing energies and structures of models of the super
silyl-cation and -enol ether to the TMS-cation and -enol ether, see:
Akakura, M.; Boxer, M. B.; Yamamoto, H. ArkiVoc 2007, Part x, accepted.
(14) Zhao, Y. H.; Abraham, M. H.; Zissimos, A. M. J. Org. Chem. 2003, 68,
7368.
In summary, a very useful means to generate synthetically
important molecules in a simple one-pot procedure has been
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