Diastereo- and enantioselective ruthenium-catalyzed hydrohydroxyalkylation of 2-silyl-butadienes: Carbonyl syn -crotylation from the alcohol oxidation level

Article abstract of DOI:10.1021/ja2046028

Exposure of alcohols 2a-2j to 2-silyl-butadienes in the presence of ruthenium complexes modified by (R)-SEGPHOS or (R)-DM-SEGPHOS results in redox-triggered generation of allylruthenium-aldehyde pairs, which combine to form products of carbonyl crotylation 4a-4j in the absence of stoichiometric byproducts and with high levels of syn-diastereo- and enantioselectivity. In the presence of isopropanol under otherwise identical conditions, aldehydes 3a-3j are converted to an equivalent set of adducts 4a-4j. Whereas reactions conducted using conventional heating require 48 h, microwave irradiation enables full conversion in only 4 h. Finally, as illustrated in the conversion of adduct 4a to compounds 6a and 6b, diastereoselective hydroboration-Suzuki cross-coupling with aryl and vinyl halides followed by Fleming-Tamao oxidation enables generation of anti,syn-stereotriads found in numerous polyketide natural products.

Full text of DOI:10.1021/ja2046028

ARTICLE
pubs.acs.org/JACS
Diastereo- and Enantioselective Ruthenium-Catalyzed
Hydrohydroxyalkylation of 2-Silyl-butadienes: Carbonyl
syn-Crotylation from the Alcohol Oxidation Level
Jason R. Zbieg, Joseph Moran, and Michael J. Krische*
Department of Chemistry and Biochemistry, University of Texas at Austin, Austin, Texas 78712, United States
S Supporting Information
b
ABSTRACT: Exposure of alcohols 2aꢀ2j to 2-silyl-butadienes
in the presence of ruthenium complexes modified by (R)-
SEGPHOS or (R)-DM-SEGPHOS results in redox-triggered
generation of allylrutheniumꢀaldehyde pairs, which combine
to form products of carbonyl crotylation 4aꢀ4j in the absence of
stoichiometric byproducts and with high levels of syn-diastereo-
and enantioselectivity. In the presence of isopropanol under
otherwise identical conditions, aldehydes 3aꢀ3j are converted to
an equivalent set of adducts 4aꢀ4j. Whereas reactions conducted
using conventional heating require 48 h, microwave irradiation
enables full conversion in only 4 h. Finally, as illustrated in the conversion of adduct 4a to compounds 6a and 6b, diastereoselective
hydroborationꢀSuzuki cross-coupling with aryl and vinyl halides followed by FlemingꢀTamao oxidation enables generation of anti,
syn-stereotriads found in numerous polyketide natural products.
’ INTRODUCTION
Roughly 20% of top-selling small molecule therapeutic agents
are polyketides,1,2 and it is estimated that polyketides are 5 times
more likely to possess useful drug activity as compared to other
families of natural products.3 Among methods for polyketide
construction,4 the addition of chirally modified crotylmetal reagents
to carbonyl compounds ranks as one of the foremost strategies
used for the generation of polypropionate substructures.5ꢀ8
However, the most broadly utilized protocol of this type, Brown’s
crotylation,5b,c generates superstoichiometric quantities of a sec-
ondary alcohol byproduct, isopinocampheol, which frequently
complicates product isolation and has prevented implementa-
tion of this technology at the process level.9 Consequently,
efforts toward asymmetric carbonyl crotylation protocols con-
tinue unabated.6ꢀ8
Recently, we reported a catalytic method for anti-diastereo-
and enantioselective carbonyl crotylation from the alcohol or
aldehyde oxidation level employing R-methyl allyl acetate as the crotyl
donor.10c,d This transformation represents one among a broad,
new class of catalytic CꢀC couplings in which hydrogen ex-
change between alcohols and π-unsaturated reactants triggers
generation of electrophileꢀnucleophile pairs that combine to
form products of carbonyl addition.11,12 Whereas chirally mod-
ified iridium complexes promote such transformations with ex-
cellent control of diastereo- and enantioselectivity,10,11c,11d en-
antioselective ruthenium-catalyzedprocesseshaveprovenelusive.13
For example, in ruthenium-catalyzed butadieneꢀalcohol CꢀC
couplings, products of carbonyl crotylation appear as mixtures of
syn- and anti-diastereomers (Figure 1).13a
Figure 1. syn-Diastereo- and enantioselective carbonyl crotylation in
the absence of stoichiometric byproducts via ruthenium-catalyzed
hydrohydroxyalkylation of 2-silyl-butadienes.
The low levels of diastereoselectivity associated with butadiene
mediated crotylations are attributed to incomplete partitioning of
Received: March 25, 2011
Published: May 31, 2011
r
2011 American Chemical Society
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Table 1. syn-Diastereo- and Enantioselective Carbonyl
generation of “pseudo-(Z)-σ-crotylruthenium” isomers, potentially
generating products of carbonyl syn-crotylation.14 Here, we report
that upon exposure of primary alcohols 2aꢀ2j to 2-silyl-butadiene 1
in the presence of chirally modified ruthenium catalysts, products of
carbonyl crotylation 4aꢀ4j are formed with high levels of syn-
diastereo- and enantioselectivity. Under related transfer hydrogena-
tion conditions employing isopropanol as terminal reductant, alde-
hydes 3aꢀ3j are converted to an equivalent set of carbonyl
crotylation products 4aꢀ4j with comparable levels of stereoselectiv-
ity (Table 2).
Crotylation from the Alcohol Oxidation Levela
’ RESULTS AND DISCUSSION
In an initial set of experiments, a range of 2-silyl-substituted
dienes were assayed for their ability to engage in efficient, syn-
diastereoselective carbonyl crotylation from the alcohol oxida-
tion level. Such dienes are conveniently prepared from the
Grignard reagent derived from chloroprene, which itself is
generated in situ from 3,4-dichloro-1-butene.15 It was found that
upon exposure of the 2-silyl-substituted butadiene 1 to aliphatic
alcohol 2j in the presence of RuHCl(CO)(PPh3)3, rac-BINAP,
in THF solvent at 95 °C, the desired product of syn-crotylation 4j
was obtained as a single diastereomer in 25% yield. It should be
noted that large alkyl substituents (for example, mesityl) at
the 2-position of butadiene also enforce syn-diastereoselectivity.
Encouraged by these results, an assay of chiral ligands was
undertaken. Remarkably, although a racemic background reac-
tion is catalyzed by RuHCl(CO)(PPh3)3, the catalyst modified
by (R)-DM-SEGPHOS [(R)-(+)-5,5-bis(di[3,5-xylyl]phosphino)-
4,4-bi-1,3-benzodioxole] promotes the reaction in 34% yield,
>20:1 dr, and 84% ee. In an effort to exclude triphenylphosphine,
and potentially eliminate a competing background reaction, the
phosphine-free precatalyst RuCl2(CO)(cymene) was assayed in
combination with (R)-DM-SEGPHOS. However, conversion
was low. In toluene, a less Lewis basic solvent, using RuHCl-
(CO)(PPh3)3 as precatalyst, the yield of 2j was significantly
improved (66% yield, >20:1 dr, 86% ee). Under these conditions,
diene 1 was coupled to a diverse range of alcohols 2aꢀ2j. The
products of crotylation 4aꢀ4j were formed in good yields and
with excellent control of syn-diastereo- and enantioselectivity
(Table 1).
Reactions conducted using conventional heating typically
require 48 h to reach full conversion. However, microwave
irradiation promotes a dramatic increase in rate. For example,
in a microwave reactor under otherwise standard conditions, the
coupling of 2-silyl-butadiene 1 to alcohol 2d is complete in only
4 h. The reaction product 4d is isolated in 88% yield with
complete syn-diastereoselectivity (>20:1 dr) and exceptional
levels of enantioselectivity (93% ee) (eq 1).
a Ligand A = (R)-DM-SEGPHOS, ligand B = (R)- SEGPHOS. Yields are
1
of isolated material. Diastereoselectivity was determined through H
NMR analysis of crude reaction mixtures. Enantiomeric excess was
determined by chiral stationary phase HPLC analysis. See the Support-
ing Information for details. (b) 250 mol % 1. (c) THF. (d) 7 mol %
catalyst.
The reductive coupling of 2-silyl-butadiene 1 to aldehydes was
attempted next. Toward this end, formic acid, 1,4-butanediol,
and isopropanol were assayed as terminal reductants under
conditions otherwise identical to those established for reactions
conducted from the alcohol oxidation level. Using isopropanol
(Z)- and (E)-σ-crotylruthenium intermediates, which react stereo-
specifically through closed transition structures to deliver syn- and
anti-diastereomers, respectively. It was reasoned that 2-silyl-substi-
tuted butadienes, readily prepared from chloroprene, would enforce
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Table 2. syn-Diastereo- and Enantioselective Carbonyl
Scheme 1. Diastereoselective Hydroboration Enables
Crotylation from the Aldehyde Oxidation Levela
Formation of anti,syn-Stereotriadsa
a Reagents:(a) TBSCl (120 mol %), imidazole(150 mol%), DMF, 25°C,
81% yield; (b) 9-BBN (300 mol %), THF, 55 °C; (c) 3-bromoanisole
(250 mol %), NaOH (330 mol %), Pd(PPh3)4 (10 mol %), THFꢀH2O,
70 °C, 75% yield 5a (over two steps); (c0) vinyl bromide (250 mol %),
NaOH (330 mol %), Pd(PPh3)4 (10 mol %), THFꢀH2O, 70 °C, 56%
yield 5b (over two steps); (d) KH (600 mol %), tBuOOH (600 mol %),
TBAF (300 mol %), NMP, 70 °C, 86% yield 6a, 77% yield 6b.
Figure 2. Stereochemical model for 2-silyl-butadiene-mediated syn-
crotylation employing a (R)-DM-SEGPHOS modified ruthenium
catalyst.
To illustrate the utility of the coupling products, compound 4a
was converted to the silyl ether and subjected to diastereoselec-
tive hydroborationꢀSuzuki cross-coupling with aryl halides and
vinyl halides to furnish adducts 5a and 5b, respectively.16
Protection of the hydroxyl moiety of 4a as the TBS is required
to enforce high levels of diastereoselectivity (10:1 dr) in the
hydroboration event. The benzyl ether derived from 4a displays
low levels of diastereoselectivity (2:1 dr) upon hydroboration
under identical conditions. FlemingꢀTamao oxidation of the
CꢀSi bond was especially challenging. However, upon exposure
of the Suzuki coupling products 5a and 5b to Woerpel’s modified
conditions for oxidative CꢀSi bond cleavage,17 the diols 6a and
6b, which possess anti,syn-stereotriads found in numerous poly-
ketide natural products, could be isolated in good yield (Scheme 1).
Finally, if products of conventional syn-crotylation are desired,
direct addition of TBAF to the reaction mixture enables proto-
desilylation in a convenient one-pot procedure, as demonstrated
by the formation of 7a (eq 2).
a Ligand A = (R)-DM-SEGPHOS, ligand B = (R)- SEGPHOS. Yields are
of isolated material. Diastereoselectivity was determined through 1H NMR
analysis of crude reaction mixtures. Enantiomeric excess was determined by
chiral stationary phase HPLC analysis. See the Supporting Information for
details. (b) 250 mol % 1. (c) THF. (d) 7 mol % catalyst. (e) 72 h.
With regard to mechanism, the stoichiometric reaction of
RuHCl(CO)(PPh3)3 with 1,2- and 1,3-dienes to form π-allyl
complexes that have been characterized by single crystal X-ray
diffraction and NMR, respectively, is known (Figure 2).18 Car-
bonyl addition by way of the σ-bound allylruthenium haptomer
through a closed transition structure delivers the homoallylic ru-
thenium alkoxide, which upon substitution with a reactant alco-
hol provides a pentacoordinate ruthenium alkoxide. The vacant
coordination site at this stage enables dehydrogenation to form
(200 mol %) as terminal reductant, diene 1 participates in highly
regio-, diastereo-, and enantioselective couplings to aldehydes
3aꢀ3j to furnish an identical set of homoallylic alcohols 4aꢀ4j in
roughly equivalent isolated yields (Table 2).
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Scheme 2. Proposed Catalytic Mechanism for
’ ACKNOWLEDGMENT
Ruthenium-Catalyzed Diene Hydrohydroxymethylation
As Supported by Established Stoichiometric Transformations
The Robert A. Welch Foundation (F-0038), the NIH-NIGMS
(RO1-GM069445), and the UT Austin, Center for Green
Chemistry and Catalysis are acknowledged for financial support.
The Natural Sciences and Engineering Research Council of
Canada (NSERC) is acknowledged for generous postdoctoral
support (J.M.).
’ REFERENCES
(1) For selected reviews on polyketide natural products, see: (a)
O’Hagan, D. The Polyketide Metabolites; Ellis Horwood: Chichester,
U.K., 1991. (b) Polyketides Biosynthesis, Biological Activity, and Genetic
Engineering; Rimando, A. M., Baerson, S. R., Eds.; ACS Symposium
Series 955; American Chemical Society: Washington, DC, 2007.
(2) (a) Newman, D. J.; Cragg, G. M. J. Nat. Prod. 2007, 70, 461. (b)
Newman, D. J.; Grothaus, P. G.; Cragg, G. M. Chem. Rev. 2009, 109, 3012.
(3) Rohr, J. Angew. Chem., Int. Ed. 2000, 39, 2847.
(4) For selected reviews on synthetic methods for polyketide
construction, see: (a) Paterson, I.; Doughty, V. A.; Florence, G.; Gerlach,
K.; McLeod, M. D.; Scott, J. P.; Trieselmann, T. ACS Symp. Ser. 2001,
783, 195. (b) Koskinen, A. M. P.; Karisalmi, K. Chem. Soc. Rev. 2005,
34, 677. (c) Yeung, K.-S.; Paterson, I. Chem. Rev. 2005, 105, 4237. (d)
Schetter, B.; Mahrwald, R. Angew. Chem., Int. Ed. 2006, 45, 7506. (e)
Morris, J. C.; Nicholas, G. M.; Phillips, A. J. Nat. Prod. Rep. 2007, 24, 87.
(f) Paterson, I. Total Synthesis of Polyketides using Asymmetric Aldol
Reactions. In Asymmetric Synthesis, 2nd ed.; Christmann, M., Br€ase, S.,
Eds.; Wiley-VCH Verlag GmbH & Co.: Weinheim, Germany, 2008; pp
293ꢀ298. (g) Paterson, I.; Findlay, A. D. Aust. J. Chem. 2009, 62, 624.
(5) For enantioselective carbonyl additions of chirally modified
crotylmetal reagents, see: (a) Hoffmann, R. W.; Ladner, W. Tetrahedron
Lett. 1979, 20, 4653. (b) Brown, H. C.; Bhat, K. S. J. Am. Chem. Soc. 1986,
108, 293. (c) Brown, H. C.; Bhat, K. S. J. Am. Chem. Soc. 1986, 108, 5919.
(d) Roush, W. R.; Halterman, R. L. J. Am. Chem. Soc. 1986, 108, 294. (e)
Roush, W. R.; Ando, K.; Powers, D. B.; Palkowitz, A. D.; Halterman,
R. L. J. Am. Chem. Soc. 1990, 112, 6339. (f) Garcia, J.; Kim, B.-M.;
Masamune, S. J. Org. Chem. 1987, 52, 4831. (g) Burgos, C. H.; Canales,
E.; Matos, K.; Soderquist, J. A. J. Am. Chem. Soc. 2005, 127, 8044. (h)
Riediker, M.; Duthaler, R. O. Angew. Chem., Int. Ed. Engl. 1989, 28, 494.
(i) Hafner, A.; Duthaler, R. O.; Marti, R.; Rihs, G.; Rothe-Streit, P.;
Schwarzenbach, F. J. Am. Chem. Soc. 1992, 114, 2321. (j) Panek, J. S.;
Yang, M. J. Am. Chem. Soc. 1991, 113, 6594. (k) Hu, T.; Takenaka, N.;
Panek, J. S. J. Am. Chem. Soc. 2002, 124, 12806. (l) Hackman, B. M.;
Lombardi, P. J.; Leighton, J. L. Org. Lett. 2004, 6, 4375. (m) Kim, H.; Ho,
S.; Leighton, J. L. J. Am. Chem. Soc. 2011, 133, 6517.
(6) For enantioselective Lewis acid-catalyzed carbonyl additions of
crotylmetal reagents, see: (a) Furuta, K.; Mouri, M.; Yamamoto, H.
Synlett 1991, 561. (b) Yanagasawa, A.; Ishiba, A.; Nakashima, H.;
Yamamoto, H. Synlett 1997, 88. (c) Yanagasawa, A.; Kageyama, H.;
Nakatsuka, Y.; Asakawa, K.; Matsumoto, Y.; Yamamoto, H. Angew.
Chem., Int. Ed. 1999, 38, 3701. (d) Aoki, S.; Mikami, K.; Terada, M.;
Nakai, T. Tetrahedron Lett. 1993, 49, 1783. (e) Motoyama, Y.; Okano,
M.; Narusawa, H.; Makihara, N.; Aoki, K.; Nishiyama, H. Organome-
tallics 2001, 20, 1580. (f) Evans, D. A.; Aye, Y.; Wu, J. Org. Lett. 2006,
8, 2071. (g) Rauniyar, V.; Hall, D. G. Angew. Chem., Int. Ed. 2006,
45, 2426. (h) Rauniyar, V.; Zhai, H.; Hall, D. G. J. Am. Chem. Soc. 2008,
130, 8481.
an aldehyde and regenerate the ruthenium hydride to close the
catalytic cycle (Scheme 2). The stereochemical outcome of the
reaction may be predicted on the basis of the indicated model
(Figure 2). Absolute and relative stereochemistry of adducts
4aꢀ4j was assigned in analogy to 7a, which was compared to an
authentic sample.7c
’ CONCLUSION
In summary, exposure of alcohols 2aꢀ2j to 2-silyl-butadiene 1
in the presence of the ruthenium catalyst obtained upon the
combination of RuHCl(CO)(PPh3)3 and (R)-SEGPHOS or
(R)-DM-SEGPHOS provides products of hydrohydroxyalkyla-
tion 4aꢀ4j with complete regioselectivity and with good to ex-
cellent levels of diastereo- and enantioselectivity. In the presence
of isopropanol, but under otherwise identical conditions, an
equivalent set of adducts 4aꢀ4j are generated in an equally se-
lective fashion from aldehydes 3aꢀ3j. In this way, catalytic syn-
diastereo- and enantioselective carbonyl crotylation is achieved
from the alcohol or aldehyde oxidation level. This carbonyl
crotylation protocol circumvents stoichiometric byproducts
and cryogenic conditions and does not require glovebox techni-
ques, thus representing an important step toward the develop-
ment of scalable methods for the construction of polyketide
natural products and related compounds. However, many unmet
challenges remain, including the development of second genera-
tion catalysts that promote efficient, stereoselective couplings to
R-chiral alcohols and aldehydes, and that enable related imine
additions from the amine oxidation level. Future studies will
address these goals.
’ ASSOCIATED CONTENT
S
Supporting Information. Experimental procedures and
b
(7) For enantioselective Lewis base-catalyzed carbonyl additions of
crotylmetal reagents, see: (a) Denmark, S. E.; Coe, D. M.; Pratt, N. E.;
Griedel, B. D. J. Org. Chem. 1994, 59, 6161. (b) Denmark, S. E.; Coe,
D. M.; Pratt, N. E.; Griedel, B. D. J. Org. Chem. 2001, 59, 6161. (c)
Denmark, S. E.; Fu, J. J. Am. Chem. Soc. 2001, 123, 9488. (d) Iseki, K.;
Kuroki, Y.; Takahashi, M.; Kishimoto, S.; Kobayashi, Y. Tetrahedron
1997, 53, 3513. (e) Nakajima, M.; Saito, M.; Shiro, M.; Hashimoto, S.-I.
J. Am. Chem. Soc. 1998, 120, 6419. (f) Malkov, A. V.; Dufkovꢀa, L.;
Farrugia, L.; Koꢁcovsky, P. Angew. Chem., Int. Ed. 2003, 42, 3674.
spectral data for all new compounds (1H NMR, 13C NMR, IR,
HRMS). This material is available free of charge via the Internet
at http://pubs.acs.org.
’ AUTHOR INFORMATION
Corresponding Author
mkrische@mail.utexas.edu
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(8) For enantioselective catalytic carbonyl crotylation via Nozakiꢀ
Hiyama coupling, see: (a) Bandini, M.; Cozzi, P. G.; Umani-Ronchi, A.
Polyhedron 2000, 19, 537. (b) Bandini, M.; Cozzi, P. G.; Umani-Ronchi,
A. Tetrahedron 2001, 57, 835. (c) Bandini, M.; Cozzi, P. G.; Umani-
Ronchi, A. Angew. Chem., Int. Ed. 2000, 39, 2327. (d) Inoue, M.; Suzuki,
T.; Nakada, M. J. Am. Chem. Soc. 2003, 125, 1140. (e) Lee, J.-Y.; Miller,
J. J.; Hamilton, S. S.; Sigman, M. S. Org. Lett. 2005, 7, 1837. (f)
McManus, H. A.; Cozzi, P. G.; Guiry, P. J. Adv. Synth. Catal. 2006,
348, 551. (g) Xia, G.; Yamamoto, H. J. Am. Chem. Soc. 2006, 128, 2554.
(9) In Brown’s allylation protocol, the stoichiometric generation of
isopinocampheol frequently complicates product isolation: (a) Ireland,
R. E.; Armstrong, J. D., III; Lebreton, J.; Meissner, R. S.; Rizzacasa, M. A.
J. Am. Chem. Soc. 1993, 115, 7152. (b) Burova, S. A.; McDonald, F. E.
J. Am. Chem. Soc. 2004, 126, 2495. (c) Ramachandran, P. V.; Prabhudas,
B.; Chandra, J. S.; Reddy, M. V. R. J. Org. Chem. 2004, 69, 6294. (d)
White, J. D.; Hansen, J. D. J. Org. Chem. 2005, 70, 1963. (e) Gao, D.;
O’Doherty, G. A. Org. Lett. 2005, 7, 1069. (f) Gao, D.; O’Doherty, G. A.
J. Org. Chem. 2005, 70, 9932. (g) Liu, D.; Xue, J.; Xie, Z.; Wei, L.; Zhang,
X.; Li, Y. Synlett 2008, 1526.
(16) For a related diastereoselective hydroborationꢀSuzuki cross-
coupling sequence, see: Coleman, R. S.; Gurrala, S. R. Org. Lett. 2005,
7, 1849.
(17) Smitrovich, J. H.; Woerpel, K. A. J. Org. Chem. 1996, 61, 6044.
(18) (a) Hiraki, K.; Ochi, N.; Sasada, Y.; Hayashida, H.; Fuchita, Y.;
Yamanaka, S. J. Chem. Soc., Dalton Trans. 1985, 873. (b) Xue, P.; Bi, S.;
Sung, H. H. Y.; Williams, I. D.; Lin, Z.; Jia, G. Organometallics 2004,
23, 4735.
(10) For enantioselective allylation, anti-crotylation, and tert-preny-
lation via iridium catalyzed alcohol-mediated CꢀC couplings, see: (a)
Kim, I. S.; Ngai, M.-Y.; Krische, M. J. J. Am. Chem. Soc. 2008, 130, 6340.
(b) Kim, I. S.; Ngai, M.-Y.; Krische, M. J. J. Am. Chem. Soc. 2008,
130, 14891. (c) Kim, I. S.; Han, S.-B.; Krische, M. J. J. Am. Chem. Soc.
2009, 131, 2514. (d) Gao, X.; Townsend, I. A.; Krische, M. J. J. Org.
Chem. 2011, 76, 2350. (e) Han, S. B.; Kim, I.-S.; Han, H.; Krische, M. J.
J. Am. Chem. Soc. 2009, 131, 6916.
(11) For recent reviews on CꢀC bond forming hydrogenation and
transfer hydrogenation, see: (a) Patman, R. L.; Bower, J. F.; Kim, I. S.;
Krische, M. J. Aldrichimica Acta 2008, 41, 95. (b) Bower, J. F.; Kim, I. S.;
Patman, R. L.; Krische, M. J. Angew. Chem., Int. Ed. 2009, 48, 34. (c) Han,
S. B.; Kim, I. S.; Krische, M. J. Chem. Commun. 2009, 7278. (d) Bower,
J. F.; Krische, M. J. Top. Organomet. Chem. 2011, 43, 107.
(12) In related “hydrogen auto-transfer” or “borrowing hydrogen”
processes, alcohol dehydrogenation and nucleophile generation occur
independently. Hence, conventional preactivated nucleophiles are re-
quired. Such processes deliver products of formal alcohol substitution
rather than carbonyl addition. For selected reviews, see: (a) Guillena, G.;
Ramꢀon, D. J.; Yus, M. Angew. Chem., Int. Ed. 2007, 46, 2358. (b) Hamid,
M. H. S. A.; Slatford, P. A.; Williams, J. M. J. Adv. Synth. Catal. 2007,
349, 1555. (c) Nixon, T. D.; Whittlesey, M. K.; Williams, J. M. J. Dalton
Trans. 2009, 753. (d) Dobereiner, G. E.; Crabtree, R. H. Chem. Rev.
2010, 110, 681. (e) Guillena, G.; Ramꢀon, D. J.; Yus, M. Chem. Rev. 2010,
110, 1611. (f) Related dehydrogenative couplings of amines also require
pre-activated nucleophiles, see: Li, C.-J. Acc. Chem. Res. 2009, 42, 335.
(13) For ruthenium catalyzed alcohol-mediated CꢀC coupling, see:
(a) Dienes, Shibahara, F.; Bower, J. F.; Krische, M. J. J. Am. Chem. Soc.
2008, 130, 6338. (b) Shibahara, F.; Bower, J. F.; Krische, M. J. J. Am.
Chem. Soc. 2008, 130, 14120. (c) Han, H.; Krische, M. J. Org. Lett. 2010,
12, 2844. (d) Smejkal, T.; Han, H.; Breit, B.; Krische, M. J. J. Am. Chem.
Soc. 2009, 131, 10366. (e) Alkynes, Patman, R. L.; Chaulagain, M. R.;
Williams, V. M.; Krische, M. J. J. Am. Chem. Soc. 2009, 131, 2066. (f)
Williams, V. M.; Leung, J. C.; Patman, R. L.; Krische, M. J. Tetrahedron
2009, 65, 5024. (g) Allenes:Skucas, E.; Zbieg, J. R.; Krische, M. J. J. Am.
Chem. Soc. 2009, 131, 5054. (h) Zbieg, J. R.; McInturff, E. L.; Krische,
M. J. Org. Lett. 2010, 12, 2514. (i) Zbieg, J. R.; McInturff, E. L.; Leung,
J. C.; Krische, M. J. J. Am. Chem. Soc. 2011, 133, 1141.
(14) Related Me3Si-substituted crotylmagnesium and crotylzinc re-
agents react with aldehydes to give racemic syn-adducts: (a) Sato, F.;
Kusakabe, M.; Kobayashi, Y. J. Chem. Soc., Chem. Commun. 1984, 1130.
(b) Helm, M. D.; Mayer, P.; Knochel, P. Chem. Commun. 2008, 1916.
(15) As practiced industrially, chloroprene is generated in situ from
3,4-dichloro-1-butene, which, in turn, derives from 1,3-butadiene. For
conversion of chloroprene to the 2-silyl substituted by way of the
Grignard reagent, see: Pidaparthi, R. R.; Junker, C. S.; Welker, M. E.;
Day, C. S.; Wright, M. W. J. Org. Chem. 2009, 74, 8290. See the
Supporting Information for experimental details related to the prepara-
tion of silyl diene 1.
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