C O M M U N I C A T I O N S
Table 2. Mitsunobu Productsa
Note Added after ASAP Publication. After this paper was
published ASAP on December 13, 2004, the chemical notation in
the Scheme 1 footnote, step (b), was changed. The corrected version
was posted December 15, 2004.
Supporting Information Available: Experimental details and
spectral characterization for all compounds. This material is available
References
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a Reactions performed with 1 equiv of ROH (0.1 mmol), 1.01-1.2 equiv
of acid, 2 equiv of OTPP, and 2 equiv of HO-DEAD at 25 °C. b Isolated
yield after second filtration with 4:1 heptane/EtOAc. c HO-DEAD with 1.5
mmol/g load. d HO-DEAD with 2.6 mmol/g load. e 1 equiv of acid and 1.02
f
equiv of alcohol. 1H NMR of isolated product showed 15% 3-phenylpropyl
ether, which could not be separated.
phenylphosphine (LPS-PPh3)17 (2 equiv) resulted in only 47%
conversion (49% yield).
In comparison studies, we employed the use of HO-DEAD in
conjunction with JandaJel-PPh3 (JJ-PPh3)18 and solid-supported
PPh3 (PS-PPh3) as well as the implementation of OTPP with PS-
DEAD (Table 1).19 More dilute conditions were required in the re-
actions with JJ-PPh3 and PS-DEAD because of the large amount of
swelling associated with these insoluble resins. JJ-PPh3, while suc-
cessful in mediating the reaction, resulted in only 50% conversion
to 9. HoweVer, both PS-PPh3 and PS-DEAD failed to produce 9.
Having found that the use of 2 equiv of both 2 and 4 were the
optimal conditions, we investigated the use of these reagents in
the Mitsunobu reaction between various nucleophiles and alcohols
(Table 2). Overall, the Mitsunobu products were isolated in 69-
90% yield, with the load of 4 having little effect on product yield.
In conclusion, we have demonstrated the viability of a multi-
polymer platform for transforming small molecules through the
development of a Mitsunobu reaction system that simultaneously
utilizes two polymer-supported reagents. This method allows for
facile product isolation compared to traditional methods. We are
currently examining additional details, expanding substrate scope,
and investigating heretofore unrealized multipolymer reactions.
Acknowledgment. This work was generously supported by
funds provided by the National Science Foundation (Career
9984926), the University of Kansas Research Development Fund,
the National Institutes of Health (KU Chemical Methodologies and
Library Development Center of Excellence, P50 GM069663), the
ACS Division of Organic Chemistry for a Nelson J. Leonard
Fellowship sponsored by Organic Syntheses, Inc. (A.M.H.), Materia,
Inc. for supplying catalyst, and the Research Grants Council
(P.H.T.: Project No. HKU 7027/03P) of the Hong Kong Special
Administrative Region, P. R. of China.
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(16) The oligomeric triphenylphosphine (OTPP, 2) has a theoretical loading
of 2.8 mmol/g with no phosphine oxide present as determined by 31P NMR
analysis. The hydrogenated oligomeric azodicarboxylate (HO-DEAD, 4)
was isolated as a free-flowing yellow solid (Figure 2) with a loading of
1.5-2.6 mmol/g as calculated using the procedure reported in ref 13.
(17) Choi, M. K. W.; He, H. S.; Toy, P. H. J. Org. Chem. 2003, 68, 9831-9834.
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(19) JJ-PPh3 was prepared as described in ref 17 and had a loading of 1.54
mmol/g. PS-PPh3 was obtained from Aldrich and had a loading of ∼3
mmol/g. PS-DEAD was obtained from Novabiochem and had a loading
of 1.3 mmol/g.
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