C O M M U N I C A T I O N S
these conditions, but (Z)-17 is the sole amination product.14
Independent experiments demonstrate that trans-15 is unreactive
with either Pd(OAc)2 or PdCl2(CH3CN)2 as the catalyst. The
formation of (Z)-17 is explained by cis-aminopalladation of cis-15
followed by â-hydride elimination from intermediate A (Scheme
2). By extension, aminoacetoxylation of cis-15 is proposed to
proceed via cis-aminopalladation followed by oxidative cleavage
of the Pd-C bond with inversion of stereochemistry at carbon.
significant potential synthetic utility, for example, in the synthesis
of amino alcohols and unnatural amino acids. Also, the mechanistic
insights provide a foundation for the development of enantio-
selective reactions.
Acknowledgment. We thank I. A. Guzei for assistance with
X-ray crystallography, and L. M. Huffman for help with 1D
NOESY experiments. This work was supported by the Dreyfus
Foundation (Teacher-Scholar Award) and NIH (RO1 GM67173).
Supporting Information Available: Experimental details and
spectroscopic and analytical data for all new compounds (PDF). This
References
The proposed intermediacy of a Pd(IV) intermediate in this
reaction (B, Scheme 2) finds substantial support from the recent
work of Sanford and Canty, who have isolated related organo-
palladium(IV) products upon oxidation of Pd(II) species with
PhI(OAc)2 and peroxide oxidants.8c,19 In a recent study of C-O
reductive elimination from a PdIV(Ar)(OAc) complex, Sanford and
co-workers provide evidence for a concerted, three-centered mech-
anism (Figure 1A). In contrast, C-O reductive elimination from
alkylplatinum(IV) species has been shown to proceed by an SN2
mechanism.20 The different mechanisms could arise from an
intrinsic difference between Pd and Pt or a difference between the
reductive elimination of M-C(aryl) versus M-C(alkyl) bonds. The
present data, which provide evidence for an SN2 mechanism (i.e.,
inversion of stereochemistry), support the latter hypothesis. The
difference probably has a stereoelectronic origin associated with
the orientation and steric accessibility of the carbon-centered orbital
involved in the C-O bond-forming step.
A cis-aminopalladation step arising from alkene insertion into a
Pd-N bond provides a rationale for the extremely high diastereo-
selectivity observed in the aminoacetoxylation of allylic ether
substrates 9-14 (Table 2, entries 8-13). Coordination of the
oxygen atom during the alkene insertion step orients the allylic
substituent over the phthalimide group, and formation of the syn
product is disfavored for steric reasons (Figure 2).
(1) Takacs, J. M.; Jiang, X.-t. Curr. Org. Chem. 2003, 7, 369-396 and
references therein.
(2) Weissermel, K.; Arpe, H.-J. Industrial Organic Chemistry, 4th ed.; Wiley-
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J. Am. Chem. Soc. 2005, 127, 2868-2869.
(4) For Pd-catalyzed intermolecular oxidative amination of activated alkenes
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(11) For selected reviews, see: (a) Kolb, H. C.; VanNieuwenhze, M. S.;
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Chem. Soc. ReV. 2004, 33, 166-174.
(12) The recently discovered Pd-catalyzed dialkoxylation of 2-vinylphenols
proceeds by yet another mechanism involving quinone methide intermedi-
ates: Schultz, M. J.; Sigman, M. S. J. Am. Chem. Soc. 2006, 128, 1460-
1461.
In summary, we have demonstrated the ability of simple Pd(II)
complexes to catalyze intermolecular aminoacetoxylation of ter-
minal alkenes. The present requirement for excess alkene substrate
represents a current limitation; however, the extremely high levels
of regio- and diastereoselectivity in these reactions underlie their
(13) For an exception in which Os-catalyzed aminohydroxylation of styrenes
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(14) See Supporting Information for details.
(15) Sorensen et al. note that cis-aminopalladation of the alkene is also possible
(see footnote 12 in ref 5).
(16) The aldol-based “erythro” designation is used for this compound in
conformance with the nomenclature employed in the original characteriza-
tion of this compound prepared by another method. See Supporting
Information for details.
Figure 1. Mechanistic differences between C(aryl)-O (A) and C(alkyl)-O
(B) reductive elimination from PdIV, which proceeds by a concerted three-
centered transition state and an SN2 pathway, respectively.
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Am. Chem. Soc. 2005, 127, 17778-17788. (d) Nakhla, J. S.; Kampf, J.
W.; Wolfe, J. P. J. Am. Chem. Soc. 2006, 128, 2893-2901.
(18) The oxidative cleavage of PdII-C bonds can occur with retention or
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(19) (a) Canty, A. J.; Denney, M. C.; Skelton, B. W.; White, A. H.
Organometallics 2004, 23, 1122-1131. (b) Canty, A. J.; Denney, M. C.;
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(20) (a) Williams, B. S.; Goldberg, K. I. J. Am. Chem. Soc. 2001, 123, 2576-
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Ed. 1998, 37, 2181-2192 and references therein.
Figure 2. Stereochemical model for the diastereoselectivity observed in
the aminoacetoxylation of allylic ethers possessing a substituent, R, in the
allylic position.
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