P-chiral, monodentate ferrocenyl phosphines, novel ligands for asymmetric catalysis

Article abstract of DOI:10.1021/jo0264123

Eight P-chiral monodentate ferrocenyl phosphines (1a-h) were prepared in high enantiomeric excess (>95% ee in most cases) by way of an ephedrine-based oxazaphospholidine borane complex. Primary alkyl, secondary alkyl, and substituted aromatic substituents were successfully introduced at the phosphorus center, along with ferrocenyl and phenyl groups, generating phosphines of the general structure FcP(Ph)(R) (Fc = ferrocenyl, R = aryl, alkyl). The synthetic route employed provides facile access to a previously undeveloped class of chiral monophosphines. These compounds were evaluated as ligands in asymmetric catalytic reductive coupling of alkynes and aldehydes and were found to provide the desired chiral allylic alcohols with good regioselectivity and ee in many cases and with complete (E)-selectivity (>98:2) in all cases.

Full text of DOI:10.1021/jo0264123

P -Ch ir a l, Mon od en ta te F er r ocen yl P h osp h in es, Novel Liga n d s for
Asym m etr ic Ca ta lysis†
Elizabeth A. Colby and Timothy F. J amison*
Massachusetts Institute of Technology, Department of Chemistry, Cambridge, Massachusetts 02139
tfj@mit.edu
Received September 6, 2002
Eight P-chiral monodentate ferrocenyl phosphines (1a -h ) were prepared in high enantiomeric excess
(>95% ee in most cases) by way of an ephedrine-based oxazaphospholidine borane complex. Primary
alkyl, secondary alkyl, and substituted aromatic substituents were successfully introduced at the
phosphorus center, along with ferrocenyl and phenyl groups, generating phosphines of the general
structure FcP(Ph)(R) (Fc ) ferrocenyl, R ) aryl, alkyl). The synthetic route employed provides
facile access to a previously undeveloped class of chiral monophosphines. These compounds were
evaluated as ligands in asymmetric catalytic reductive coupling of alkynes and aldehydes and were
found to provide the desired chiral allylic alcohols with good regioselectivity and ee in many cases
and with complete (E)-selectivity (>98:2) in all cases.
In tr od u ction
coupling reactions, and R-isocyanocarboxylate aldol reac-
tions.5,6 We have found that achiral ferrocenyl phos-
phines (e.g., FcPPh2, Fc ) ferrocenyl)7 promote nickel-
catalyzed, intermolecular reductive coupling reactions of
alkynes and aldehydes.8 Taking FcPPh2 as a lead struc-
ture, we targeted several P-chiral ferrocenyl phosphines
in order to investigate their steric and electronic effects
on these and other catalytic reactions. Compounds 1a -h
(Chart 1) are representative members of a class of
P-chiral monodentate phosphines that has not been
thoroughly explored to date.9
Chiral phosphines have proven to be effective and
highly selective ligands for a wide variety of enantio-
selective transition metal-catalyzed reactions.1 Since the
introduction of DIOP in the early 1970s by Kagan,2
bidentate phosphines have been the center of consider-
able attention. The exceptional enantioselectivities ob-
served with chiral bisphosphines have often overshad-
owed the utility of chiral monophosphine ligands. Certain
metal-catalyzed reactions, however, are inhibited or
completely suppressed by bisphosphine ligands yet pro-
ceed smoothly and with high enantioselectivity when
monophosphines are used.3 Examples include rhodium-
catalyzed hydrogenation of olefins and carbonyls, pal-
ladium-catalyzed hydrosilylation of olefins, rhodium-
catalyzed hydrosilylation of carbonyls, nickel-catalyzed
cross-coupling reactions, and palladium-catalyzed allylic
substitution reactions.4
Resu lts a n d Discu ssion
Syn th esis of P -Ch ir a l, Mon od en ta te F er r ocen yl
P h osp h in es. The van Leeuwen10 and Mezzetti11 labo-
ratories recently described procedures for preparing
related bidentate P-chiral ferrocenyl bisphosphines using
J uge´’s ephedrine-based method12 for the enantioselective
synthesis of PAMP13 and other P-chiral phosphines. Our
initial investigations began with one of van Leeuwen’s
intermediates, (R)-methyl (ferrocenylphenyl)phosphinite
Monophosphines containing a ferrocenyl moiety have
been particularly effective ligands for several catalytic,
asymmetric metal-catalyzed reactions, such as dialkyl-
zinc additions to aldehydes, allylic alkylations, cross-
(5) Reviews: (a) Ferrocenes. Homogeneous Catalysis, Organic Syn-
thesis, Materials Science; Togni, A., Hayashi, T., Eds.; VCH Publish-
ers: Weinheim, 1995. (b) Richards, C. J .; Locke, A. J . Tetrahedron:
Asymmetry 1998, 9, 2377-2407.
† Dedicated to the memory of Professor Henry Rapoport.
(1) (a) Noyori, R. Asymmetric Catalysis in Organic Synthesis; Wiley
Sons: New York, 1994; Chapter 2. (b) Catalytic Asymmetric
&
Synthesis; Ojima, I., Ed.; VCH Publishers: Weinheim, 1993; Chapter
1. (c) Pietrusiewicz, K. M.; Zablocka, M. Chem. Rev. 1994, 94, 1375-
1411. (d) Ohff, M.; Holz, J .; Quirmbach, M.; Bo¨rner, A. Synthesis 1998,
1391-1415. (e) Yamanoi, Y.; Imamoto, T. Rev. Heteroat. Chem. 1999,
20, 227-248. (f) Brunel, J . M.; Buono, G. In Topics in Current
Chemistry; Springer-Verlag: New York, 2002; pp 79-105.
(2) (a) Dang, T. P.; Kagan, H. B. J . Chem. Soc., Chem. Commun.
1971, 481. (b) Kagan, H. B.; Dang, T. P. J . Am. Chem. Soc. 1972, 94,
6429-6433.
(3) (a) Komarov, I. V.; Bo¨rner, A. Angew. Chem., Int. Ed. 2001, 40,
1197-1200. (b) Van Leeuwen, P. W. N. M.; Kamer, P. C. J .; Reek, J .
N. H.; Dierkes, P. Chem. Rev. 2000, 100, 2741-2769.
(4) Recent reviews: (a) Lagasse, F.; Kagan, H. B. Chem. Pharm.
Bull. 2000, 48, 315-324. (b) Hayashi, T. Acc. Chem. Res. 2000, 33,
354-362.
(6) Asymmetric, catalytic reactions using planar-chiral phosphafer-
rocene ligands: (a) Qiao, S.; Fu, G. C. J . Am. Chem. Soc. 1941, 63,
4168-4169. (b) Tanaka, K.; Qiao, S.; Tobisu, M.; Lo, M. M.-C.; Fu, G.
C. J . Am. Chem. Soc. 2000, 122, 9870-9871. (c) Shintani, R.; Lo, M.
M-C.; Fu, G. C. Org. Lett. 2000, 2, 3695-3697 and references therein.
(7) Both achiral and chiral (racemic) ferrocenyl monophosphines are
highly effective for Pd-catalyzed arylation and cross-coupling reactions;
see: (a) Stambuli, J . P.; Stauffer, S. R.; Shaughnessy, K. H.; Hartwig,
J . F. J . Am. Chem. Soc. 2001, 123, 2677-2678. (b) Stauffer, S. R.;
Beare, N. A.; Stambuli, J . P.; Hartwig, J . F. J . Am. Chem. Soc. 2001,
123, 4641-4642. (c) Beare, N. A.; Hartwig, J . F. J . Org. Chem. 2002,
67, 541-555. (d) Kataoka, N.; Shelby, Q.; Stambuli, J . P.; Hartwig, J .
F. J . Org. Chem. 2002, 67, 5553-5566.
(8) Huang, W.-S.; Chan, J .; J amison, T. F. Org. Lett. 2000, 2, 4221-
4223.
10.1021/jo0264123 CCC: $25.00 © 2003 American Chemical Society
Published on Web 12/11/2002
156
J . Org. Chem. 2003, 68, 156-166

P-Chiral, Monodentate Ferrocenyl Phosphines
CHART 1
SCHEME 1
cursor to key intermediate 4i, was sluggish and low
yielding (approximately 30% yield of 4i, 35% recovered
3i).
Accordingly, to prepare the ligands in a quantity
suitable for thorough study, we investigated an alterna-
tive strategy that installs the ferrocenyl group later in
the synthesis.14 As shown in Scheme 1, treatment of
oxazaphospholidine borane 2 with the appropriate orga-
nolithium reagent (retention of stereochemistry)15 was
followed by acid-promoted methanolysis of the resulting
phosphinamide borane product 3 (inversion). It should
be noted that preparation of cyclohexyllithium and
2-methyl-2-phenyl-1-propyllithium (neophyllithium) was
best accomplished using a naphthalene-catalyzed oxida-
tive addition of lithium metal16 to chlorocyclohexane and
1-chloro-2-methyl-2-phenylpropane, respectively.
Methanolysis of aryl- and primary alkyl-substituted
phosphinamide boranes 3a ,b and 3d -h proceeded
smoothly, but formation of methyl-cyclohexylphenylphos-
phinite borane 4c was lower yielding. Secondary and
tertiary alkyl-substituted phosphinamide boranes are
notoriously difficult to convert to phosphinite boranes and
usually require heating to obtain the desired product,
often in low yield.17
borane (4i).10c Using this strategy (Scheme 1), the ferro-
cenyl and phenyl groups of all the ligands would be
installed first to allow for straightforward variation of
the third group from a common intermediate. However,
as observed by van Leeuwen, we found that the acid-
promoted methanolysis of phosphinamide borane 3i
((Rp,1R,2S)-N-methyl-N-(1-hydroxy-1-phenyl)prop-2-yl-P-
(ferrocenyl)-P-(phenyl)-phosphinamide borane), the pre-
(9) To the best of our knowledge, only the o-anisyl derivative 1e has
been previously reported (92% ee): (a) Brown, J . M.; Laing, J . C. P. J .
Organomet. Chem. 1997, 529, 435-444. Racemic 1a and 1b have also
been synthesized previously, but not in enantiomerically enriched form.
(b) (()-1a : Seyferth, D.; Withers, H. P., J r. Organometallics 1982, 1,
1275-1282. (c) (()-1b: Chacon, S. T.; Cullen, W. R.; Bruce, M. I.;
Shawkataly, O. B. Can. J . Chem. 1990, 68, 2001-2010.
Completion of the phosphine syntheses required in-
stallation of the ferrocenyl substituent. Although methods
of direct deprotonation of ferrocene with sec-butyllithium
or tert-butyllithium are commonly used to generate
ferrocenyllithium (FcLi), we found that FcLi prepared via
(10) (a) Nettekoven, U.; Widhalm, M.; Kamer, P. C. J .; van Leeuwen,
P. W. N. M. Tetrahedron: Asymmetry 1997, 8, 3185-3188. (b)
Nettekoven, U.; Kamer, P. C. J .; van Leeuwen, P. W. N. M.; Widhalm,
M.; Spek, A. L.; Lutz, M. J . Org. Chem. 1999, 64, 3996-4004. (c)
Nettekoven, U.; Widhalm, M.; Kalchhauser, H.; Kamer, P. C. J .; van
Leeuwen, P. W. N. M.; Lutz, M.; Spek, A. L. J . Org. Chem. 2001, 66,
759-770.
(11) Maienza, F.; Wo¨rle, M.; Steffanut, P.; Mezzetti, A.; Spindler,
F. Organometallics 1999, 18, 1041-1049.
(14) Brown used a similar approach to prepare 1e in 92% ee. See
ref 9a.
(12) J uge´, S.; Stephan, M.; Laffitte, J . A.; Geneˆt, J . P. Tetrahedron
Lett. 1990, 31, 6357-6360.
(13) PAMP was first synthesized by Knowles using a strategy
developed by Mislow, by way of an enantiomerically enriched menthyl
phosphinate. (a) Knowles, W. S.; Sabacky, M. J .; Vineyard, B. D. J .
Chem. Soc., Chem. Commun. 1972, 10-11. (b) Korpiun, O.; Lewis, R.
A.; Chickos, J .; Mislow, K. J . Am. Chem. Soc. 1968, 90, 4842-4846.
(15) J uge´, S.; Stephan, M.; Merde`s, R.; Geneˆt, J . P.; Halut-Desportes,
S. J . Chem. Soc., Chem. Commun. 1993, 531-533.
(16) Yus, M.; Ramo´n, D. J . J . Chem. Soc., Chem. Commun. 1991,
398-400.
(17) Rippert, A. J .; Linden, A.; Hansen, H.-J . Helv. Chim. Acta 2000,
83, 311-321.
J . Org. Chem, Vol. 68, No. 1, 2003 157

Colby and J amison
overall yield
TABLE 1. Su m m a r y of Syn th etic Op er a tion sa
RLi addition
yield (%)
methanolysis
compd yield (%)
FcLi addition
yield (%)
BH3 removal
yield (%)
compd
drb
9:1
compd
ee (%)c
compd
ee (%)c
(4 steps, %)
3a
3b
3c
3d
3e
3f
79
80
88
72
80
93
80
81
4a
4b
4c
4d
4e
4f
75
62
29
65
77
77
87
77
5a
5b
5c
5d
5e
5f
58
90
66
79
85
92
70
69
83
77
97
98
95
>98
83
98
1a
1b
1c
1d
1e
1f
93
88
83
>99
95
83
>99
94
>95d
80
98
96
94
>98
>98e
96
32
39
14
37
50
55
48
40
16:1
>98:2
>98:2
>98:2
>98:2
>98:2
>98:2
3g
3h
4g
4h
5g
5h
1g
1h
a
b
d
See Scheme 1. Determined by 1H NMR. c Determined by HPLC. Recrystallized from hexane. e Crystallized from diethylamine upon
standing after BH3 removal.
SCHEME 2
majority of these ligands are moderately air-stable, and
the corresponding BH3 complexes (5a -h ) are convenient
for long-term storage of these novel P-chiral phosphines
(Scheme 2).20
Asym m et r ic Ca t a lyt ic Ca r b on -Ca r b on Bon d -
F or m in g Rea ction s. Chiral allylic alcohols21 are useful
building blocks in the preparation of a variety of organic
molecules and are found in many natural products,22-24
with potential therapeutic applications. Accordingly,
several catalytic enantioselective methods of allylic al-
cohol synthesis have been described and can be divided
into three types: additions of organometallic reagents to
carbonyls, carbonyl reduction, and kinetic resolution of
chiral allylic alcohols. The first of these also forms a
carbon-carbon bond in the course of the reaction, with
the Nozaki-Hiyama-Kishi (NHK) reaction being a well-
known example,25,26 but an enantioselective version of the
NHK reaction has yet to be described.27 The methods of
Oppolzer28 and Wipf29 form a carbon-carbon bond using
different transition metals, by first preparing organome-
tallic reagents by way of hydrometalation of a terminal
metal-halogen exchange of commercially available bro-
moferrocene and tert-butyllithium provided the desired
substitution products (inversion of configuration) in
superior yields.18 The metal-halogen exchange can also
be performed with n-butyllithium, but in the case of
ferrocenylmethylphenylphosphine (1a ) we observed sig-
nificant amounts (>30%) of an n-pentyl-containing prod-
uct, which likely arose from ferrocenyl substitution,
deprotonation of one of the methyl protons, and alkyla-
tion of the resulting lithium anion by n-butyl bromide.19
In all cases, the BH3 group facilitated chromatographic
purification, providing the corresponding complexes of the
phosphines as orange, air-stable compounds. Removal of
the BH3 group by heating in the presence of diethylamine
proceeded in good to excellent yield in all cases, providing
the free phosphines. The enantiomeric excesses of 1a -h
were determined by reprotection with BH3 (retention)
and subsequent measurement via HPLC. As shown in
Scheme 2, comparison of the enantiomeric excesses of
5a -h before and after the deprotection-reprotection
sequence confirmed the preservation of stereochemical
integrity during the diethylamine-mediated BH3 removal
(below limit of detection).
(20) In two cases shown in Table 2, the diastereoselectivity of FcLi
addition (for 3b and 3g) does not agree with the enantiomeric excess
of the corresponding phosphine-borane complexes (5b and 5g). It is
possible that racemization may occur during the methanolysis step
(giving 4b and 4g) in these cases. See ref 41 for similar observations.
(21) For reviews of useful reactions of allylic alcohols, see: (a)
Bru¨ckner, R. In Comprehensive Organic Synthesis; Trost, B. M., Ed.;
Pergamon: New York, 1991; Vol. 6, Chapter 4.6, pp 873-908. (b) Hill,
R. K. In Comprehensive Organic Synthesis; Trost, B. M., Ed.; Perga-
mon: New York, 1991; Vol. 5, Chapter 7.1, pp 785-826. (c) Wipf, P.
In Comprehensive Organic Synthesis; Trost, B. M., Ed.; Pergamon:
New York, 1991; Vol. 5, Chapter 7.2, pp 827-873. (d) Hoveyda, A. H.;
Evans, D. A.; Fu, G. C. Chem. Rev. 1993, 93, 1307-1370.
(22) Terpestacin: (a) Iimura, S.; Oka, M.; Narita, Y.; Konishi, M.;
Kakisawa, H.; Gao, Q.; Oki, T. Tetrahedron Lett. 1993, 34, 493-496.
(b) Oka, M.; Iimura, S.; Tenmyo, O.; Sawada, Y.; Sugawara, M.;
Ohkusa, N.; Yamamoto, H.; Kawano, K.; Hu, S.-L.; Fukagawa, Y.; Oki,
T. J . Antibiot. 1993, 46, 367-373. (c) Oka, M.; Iimura, S.; Narita, Y.;
Furumai, T.; Konishi, M.; Oki, T.; Gao, Q.; Kakisawa, H. J . Org. Chem.
1993, 58, 1875-1881.
(23) Acutiphycin: Moore, R. E.; Patterson, G. M. L. J . Am. Chem.
Soc. 1984, 106, 8193-8197.
(24) Epothilones: Bollag, D. M.; McQueney, P. A.; Zhu, J .; Hensens,
O.; Koupal, L.; Liesch, J .; Goetz, M.; Lazarides, E.; Woods, C. M. Cancer
Res. 1995, 55, 2325-2333.
(25) (a) Okude, Y.; Hirano, S.; Hiyama, T.; Nozaki, H. J . Am. Chem.
Soc. 1977, 99, 3179-3181. (b) J in, H.; Uenishi, J .; Christ, W. J .; Kishi,
Y. J . Am. Chem. Soc. 1986, 108, 5644-5646. (c) Takai, K.; Tagashira,
M.; Kuroda, T.; Oshima, K.; Utimoto, K.; Nozaki, H. J . Am. Chem.
Soc. 1986, 108, 6048-6050. (d) Fu¨rstner, A.; Shi, N. J . Am. Chem.
Soc. 1996, 118, 2533-2534. (e) Fu¨rstner, A.; Shi, N. J . Am. Chem. Soc.
1996, 118, 12349-12357.
Summarized in Table 1 are the results obtained for the
synthesis leading to P-chiral phosphines 1a -h . The
average yield for the four-step sequences range from 75%
to 86% per step in all but one case (R ) c-C6H11, 1c), and
1b is the only ligand of the eight described that was not
afforded in g94% ee at the end of the sequence. The
(18) For other selective methods of FcLi generation, see: (a) Sanders,
R.; Mueller-Westerhoff, U. T. J . Organomet. Chem. 1996, 512, 219-
224. (b) Chieffi, A.; Comasseto, J . V.; Snieckus, V. Synlett 2000, 2, 269-
271. (c) Guillaneux, D.; Kagan, H. B. J . Org. Chem. 1995, 60, 2502-
2505.
(19) (a) Imamoto, T.; Kusumoto, T.; Suzuki, N.; Sato, K. J . Am.
Chem. Soc. 1985, 107, 5301-5303. (b) Imamoto, T.; Oshiki, T.;
Onozawa, T.; Kusumoto, T.; Sato, K. J . Am. Chem. Soc. 1990, 112,
5244-5252.
(26) For related asymmetric catalytic reaction using benzylic and
allylic Cr reagents (as opposed to vinylic) to give homoallylic alcohols
(instead of allylic alcohols), see: Bandini, M.; Cozzi, P. G.; Umani-
Ronchi, A. Polyhedron 2000, 19, 537-539.
(27) For examples of diastereoselective, catalytic couplings using
chiral ligands, see: Kishi, Y. Tetrahedron 2002, 58, 6239-6258.
158 J . Org. Chem., Vol. 68, No. 1, 2003

P-Chiral, Monodentate Ferrocenyl Phosphines
SCHEME 3
alkyne (hydroboration and hydrozirconation, respec-
tively). In each case, transmetalation with a dialkylzinc
reagent precedes addition of a chiral ligand and an
aldehyde. The disubstituted allylic alcohol products are
obtained in good to high yields and, in many cases, in
very high enantiomeric excess. These procedures are not
as effective with internal acetylenes (e.g., Ph-CtC-Me)
as interconversion of the (E) and (Z) isomers can occur
to a significant degree upon transmetalation with the
organozinc reagent.30
Chiral allylic alcohols can also be obtained by way of
in situ reductive coupling of an alkyne and an aldehyde.
Methods that involve stoichiometric use of transition
metals have been described by Buchwald,31 Living-
house,32 Negishi,33 and Takai and Utimoto.34 Sato dem-
onstrated that certain optically enriched allylic alcohols
could be obtained with stoichiometric use of chiral
titanium-alkyne complexes.35
Catalytic methods for intramolecular36 and inter-
molecular8 reductive coupling of alkynes and aldehydes
have also been described, but both of these methods are
limited to the preparation of racemic allylic alcohols.37
To date, examples of asymmetric catalytic reductive
or alkylative coupling of alkynes and aldehydes that do
not involve an initial hydrometalation of the alkyne (see
above) have not been described. Were this feasible, the
convenient functional groups of alkynes and aldehydes
could be assembled in a single catalytic operation to
provide enantiomerically enriched, chiral allylic alcohols.
In addition to enantioselectivity, the challenges associ-
ated with this approach include regioselectivity with
respect to the alkyne substituents and E/ Z-selectivity
in formation of the double bond.
Since allylic alcohols corresponding to catalytic reduc-
tive couplings between aldehydes and “alkyl-alkyl”
alkynes (alkyl-CtC-alkyl′) are commonly found in natu-
ral products and related molecules, the enantioselective
transformation depicted in Scheme 3 would constitute
an efficient and rapid entry into these important func-
tional group assemblies.21-23
reductive couplings, providing chiral allylic alcohols in
good yield and with exclusive cis addition across the
alkyne.8 Alkynes containing one aromatic subsituent or
a trimethylsilyl group (or both) were obtained in high
regioselectivity in these studies. In initial studies of
couplings of “alkyl-alkyl” alkynes (Table 2), we observed
that Bu3P was effective in this catalytic reaction (Scheme
3) but afforded allylic alcohols 6a and 6b in low regiose-
lectivity (entry 1). Similar regioselectivities were ob-
served with other achiral phosphines (entries 2-4), yet
it should be noted that in all cases the (E)-allylic alcohol
(cis addition across the alkyne) was obtained exclusively
(>98:2).
Among these achiral ligands, (ferrocenyl)diphenylphos-
phine was the most selective (FcPPh2, entry 4). Allylic
alcohols 6a and 6b were obtained in good yield, complete
(E)-selectivity, and 3:1 regioselectivity (favoring 6a ), the
highest regioselectivity we had observed up to this point
in our investigations of this particular coupling reaction.
Accordingly, as indicated above, we chose FcPPh2 as
the basis for the development of an asymmetric catalytic
variant of this transformation. In these studies of 1a -h
(entries 5-12), we found o-tolyl ligand 1g to be superior
with respect to regio- and enantioselectivity, giving an
85:15 mixture of 6a (55% ee) and 6b. Phosphines 1a (R
) Me), 1f (R ) o-anisyl), and 1g displayed nearly the
same degrees of selectivity, with 1a (entry 5) providing
the best combination among these three ligands. For
comparison, the three representative chiral monophos-
phines shown in Chart 2, (neomenthyl)diphenylphos-
phine38 (NMDPP, 11), ferrocenyl phosphine 12,39 and a
proline-derived alkyldiphenylphosphine (13),40 were used
in similar experiments (entries 13-15). With a few
exceptions, the regioselectivities and enantioselectivities
were lower than those obtained with phosphines 1a -h .
In all other catalytic coupling reactions examined to
date, phosphine 1a has afforded the highest enantio-
selectivities (entries 16, 21-23), perhaps because the
difference in steric demand of the ferrocenyl group and
Previously, we reported that tributylphosphine (Bu3P)
was an effective ligand for catalytic, intermolecular
(28) (a) Oppolzer, W.; Radinov, R. N. Helv. Chim. Acta 1992, 75,
170-173. (b) Oppolzer, W.; Radinov, R. N. J . Am. Chem. Soc. 1993,
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Chem. 2001, 66, 4766-4770.
(29) (a) Wipf, P.; Ribe, S. J . Org. Chem. 1998, 63, 6454-6455. (b)
Wipf, P.; Xu, W. Org. Synth. 1997, 74, 205-211.
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(31) Buchwald, S. L.; Watson, B. T.; Huffman, J . C. J . Am. Chem.
Soc. 1987, 10, 2544-2546.
(32) Van Wagenen, B. C.; Livinghouse, T. Tetrahedron Lett. 1989,
30, 3495-3498.
(33) Takagi, K.; Rousset, C. J .; Negishi, E. J . Am. Chem. Soc. 1991,
113, 1440-1442.
(34) Takai, K.; Kataoka, Y.; Utimoto, K. J . Org. Chem. 1990, 55,
1707-1708. (b) Kataoka, Y.; Miyai, J .; Oshima, K.; Takai, K. Utimoto,
K. J . Org. Chem. 1992, 57, 1973-1981.
(35) Takayanagi, Y.; Yamashita, K.; Yoshida, Y.; Sato, F. Chem.
Commun. 1996, 1725-1726.
(36) (a) Oblinger, E.; Montgomery, J . J . Am. Chem. Soc. 1997, 119,
9065-9066. (b) Review: Montgomery, J . Acc. Chem. Res. 2000, 33,
467-473. (c) Tang, X.-Q.; Montgomery, J . J . Am. Chem. Soc. 1999,
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2000, 122, 6950-6954. (e) Crowe, W. E.; Rachita, M. J . J . Am. Chem.
Soc. 1995, 117, 6787-6788.
(37) Montgomery has also described Ni-catalyzed three-component
assembly of allylic alcohols from alkynes, aldehydes, and organozinc
reagents (alkylative coupling). See ref 36a.
(38) Morrison, J . D.; Burnett, R. E.; Aguiar, A. M.; Morrow, C. J .;
Philips, C. J . Am. Chem. Soc. 1971, 93, 1301-1303.
(39) (a) Hayashi, T.; Konishi, M.; Fukushima, M.; Mise, T.; Kagotani,
M.; Tajika, M.; Kumada, M. J . Am. Chem. Soc. 1982, 104, 180-186.
(b) Hayashi, T.; Hayashizaki, K.; Kiyoi, T.; Ito, Y. J . Am. Chem. Soc.
1988, 110, 8153-8156.
(40) Hiroi, K.; Hidaka, A.; Sezaki, R.; Imamura, Y. Chem. Pharm.
Bull. 1997, 45, 769-777.
J . Org. Chem, Vol. 68, No. 1, 2003 159

Colby and J amison
TABLE 2a
entry
ligand
Bu3P
productb
R1
R2
R3
yield (%)c
a :bd
ee a (%)e
ee b (%)f
1
2
3
4
5
6
7
8
6a , 6b
6a , 6b
6a , 6b
6a , 6b
6a , 6b
6a , 6b
6a , 6b
6a , 6b
6a , 6b
6a , 6b
6a , 6b
6a , 6b
6a , 6b
6a , 6b
6a , 6b
7
c-C6H11
c-C6H11
c-C6H11
c-C6H11
c-C6H11
c-C6H11
c-C6H11
c-C6H11
c-C6H11
c-C6H11
c-C6H11
c-C6H11
c-C6H11
c-C6H11
c-C6H11
n-Pr
n-Pr
n-Pr
n-Pr
n-Pr
n-Pr
n-Pr
c-C6H11
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
n-Pr
n-Pr
n-Pr
n-Pr
n-Pr
n-Pr
n-Pr
Me
i-Pr
i-Pr
i-Pr
i-Pr
i-Pr
i-Pr
i-Pr
i-Pr
i-Pr
i-Pr
i-Pr
i-Pr
i-Pr
i-Pr
i-Pr
Ph
Ph
Ph
Ph
Ph
n-Pr
i-Pr
n-Pr
55
56
62
60
65
27
53
33
60
60
46
33
50
40
22
85
80
81
79
87
80
80
30
2.0:1
1.9:1
2.0:1
3.0:1
2.2:1
1.8:1
1.6:1
1:1
2.4:1
3.8:1
5.7:1
1:1
2.0:1
1:1
1.2:1
na
na
na
na
na
na
na
46
na
na
na
na
45
Ph2P(n-Bu)
Ph2P(Cy)
FcPPh2
1a
1b
1c
1d
1e
1f
1g
1h
11
12
13
1a
1c
1f
1g
8
12
-34
-44
2
-28
-55
-52
-35
-20
-35
49
-4
12
-28
-36
55
-28
-10
4
-17
-19
-37
-38
-17
-39
na
na
na
na
na
na
na
68
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
7
7
7
7
8
9
na
na
na
na
1h
1a
1a
1a
55
67
10a , 10b
2.2:1
a
All reactions were conducted using 10 mol % Ni(cod)2, 10 mol % ligand, and 200 mol % Et3B. See Scheme 3 and Experimental Section
b
for details. Regioselectivities and enantioselectivities were determined for unpurified product mixtures. Major and minor regioisomers.
See Scheme 3. c Combined yield of all allylic alcohol products. Regioselectivity (a :b) determined by 1H NMR. e Enantiomeric excess of
d
regioisomer a . Absolute configuration of 6a assigned by Mosher ester analysis. Absolute configuration of 6b, 7-9, and 10a -b assigned
by analogy. Negative signs indicate opposite sense of induction. f Enantiomeric excess of regioisomer b.
CHART 2
excess. When used as ligands in the catalytic reactions
described above, these compounds are superior in every
respect to any other class of chiral phosphine we have
evaluated for an important class of alkynes, affording
certain types of chiral allylic alcohols in good to high
yield, good regioselectivity and enantioselectivity in most
cases, and with complete (E)-selectivity (>98:2) in every
case. Our continued investigations in this area will be
facilitated by the synthetic sequence leading to ligands
1a -h , as it is amenable to steric and electronic variation
of the substituents on phosphorus. These novel P-chiral,
monodentate ferrocenyl phosphines may also find utility
in other asymmetric catalytic reactions.
SCHEME 4
Exp er im en ta l Section
Gen er a l. All reactions were carried out under an inert
atmosphere of argon using Schlenk techniques and oven-dried
glassware. Tetrahydrofuran and diethyl ether were distilled
from sodium/benzophenone ketyl. Diethylamine and methanol
were purchased in 99.5% purity and were degassed before use
by bubbling argon through for 20 min. Ethyl acetate was
distilled from CaSO4 and degassed before use by bubbling
argon through for 20 min. NMR spectra were recorded on 300
the varied group is the greatest in this case (Fc vs R )
Me). The superiority of ligand 1a and the sense of
induction observed in the formation of 6a (Mosher ester
analysis) are consistent with the model shown in Scheme
4, in which a Et3B-aldehyde complex approaches an
alkyne-Ni(0)-phosphine complex such that the Et3B group
approaches syn to a small Me group, away from a much
larger Fc group. Investigation of the mechanistic details
and further development of these novel phosphines are
ongoing in our laboratory.41
1
and 500 MHz instruments. H NMR positive chemical shifts
in ppm are downfield from tetramethylsilane; 31P NMR posi-
tive chemical shifts in ppm are downfield from an external
85% phosphoric acid standard. IR spectra were recorded on a
(41) Several mechanistic frameworks for Ni-catalyzed coupling
reactions involving carbonyl addition have been proposed. See ref 36
and (a) Tsuda, T.; Kiyoi, T.; Saegusa, T. J . Org. Chem. 1990, 55, 2554.
(b) Sato, Y.; Takimoto, M.; Hayashi, K.; Katsuhara, T.; Takagi, K.;
Mori, M. J . Am. Chem. Soc. 1994, 116, 9771. (c) Kimura, M.; Ezoe, A.;
Shibata, K.; Tamaru, Y. J . Am. Chem. Soc. 1998, 120, 4033. (d) Sato,
Y.; Takanashi, T.; Mori, M. Organometallics 1999, 18, 4891. (e) Sato,
Y.; Saito, N.; Mori, M. J . Am. Chem. Soc. 2000, 122, 2371. (f)
Chowdhury, S. K.; Amarasinghe, K. K. D.; Heeg, M. J .; Montgomery,
J . J . Am. Chem. Soc. 2000, 122, 6775. (g) Amarasinghe, K. K. D.;
Chowdhury, S. K.; Heeg, M. J .; Montgomery, J . Organometallics 2001,
20, 370.
Con clu sion s
In four steps from oxazaphospholidine-borane 2, P-
chiral ferrocenyl phosphines can be synthesized in 14-
55% overall yield and in good to very high enantiomeric
160 J . Org. Chem., Vol. 68, No. 1, 2003

P-Chiral, Monodentate Ferrocenyl Phosphines
FTIR instrument using NaCl plates. Melting points were
measured on a capillary melting point apparatus. HPLC was
performed on a chromatograph equipped with a variable
wavelength detector and Chiracel OD, OJ , or AD column (0.46
cm × 25 cm). Analysis by chiral GC was performed on a
chromatograph equipped with a Chiradex B-PH column.
(m, 1H), 1.83 (d, J ) 3.6 Hz, 1H), 1.69-1.62 (m, 1H), 1.47-
1.38 (m, 3H), 1.19 (d, J ) 6.7 Hz, 3H), 0.95 (t, J ) 7.3 Hz,
3H), 1.05-0.4 (br m, 3H). 13C NMR (CDCl3, 125 MHz): δ 143.2,
133.0 (d, J ) 60.9 Hz), 131.2, 131.11, 131.10, 129.22, 129.19,
129.14, 126.7, 127.1 (2C), 79.4 (d, J ) 4.0 Hz), 58.8 (d, J )
8.6), 30.0 (d, J ) 2.9 Hz), 25.8 (d, J ) 42.0 Hz), 25.5, 25.0 (d,
J ) 15.6 Hz), 14.4, 13.6 (d, J ) 2.8 Hz). 31P NMR (CDCl3, 121.5
MHz): δ 70.3 (br q, J ) 73 Hz). HRMS (ESI) [M + Na]+: m/z
calcd for C20H31BNNaOP 366.2129, obsd 366.2123.
(2Sp ,4R,5S)-(-)-3,4-Dim eth yl-2,5-d ip h en yl-1,3,2-oxa za -
p h osp h olid in e Bor a n e (2).12 A solution of dichlorophe-
nylphosphine (10.8 mL, 80 mmol) in 400 mL of tetrahydrofu-
ran was cooled to 0 °C. (+)-Ephedrine (13.2 g, 80 mmol) was
added in one portion, causing a white precipitate to form.
Diisopropylethylamine (28 mL, 160 mmol) was added via
syringe, and the heterogeneous mixture was allowed to warm
to ambient temperature and then refluxed 24 h (solids dis-
solved upon heating). After the mixture cooled to ambient
temperature, BH3‚THF was added (80 mL, 1.0 M in THF, 80
mmol), and the heterogeneous mixture was stirred for 18 h.
H2O was added, and the aqueous layer was extracted with
diethyl ether. The combined organic layers were washed with
saturated aqueous NaCl, dried with MgSO4, filtered, and
concentrated in vacuo. Recrystallization from methanol pro-
vided the title compound (8.57 g, 30.0 mmol, 38% yield) as a
white crystalline solid. Mp: 103-104 °C. Rf (80:20 hexane/
EtOAc) ) 0.23. IR (thin film): 3428, 2381, 1644, 1454, 1436
cm-1. 1H NMR (CDCl3, 500 MHz): δ 7.84-7.81 (m, 2H), 7.55-
7.50 (m, 3H), 7.40-7.28 (m, 5H), 5.60 (dd, J ) 3.1, 6.0 Hz,
1H), 3.71-3.67 (m, 1H), 2.69 (d, J ) 11.0 Hz, 3H), 0.84 (d, J
) 6.7 Hz, 3H), 1.3-0.7 (br m, 3H). 13C NMR (CDCl3, 125
MHz): δ 136.4 (d, J ) 5.4 Hz), 132.6 (d, J ) 2.2 Hz), 131.1 (d,
J ) 12.1 Hz, 2C), 128.8 (d, J ) 9.8 Hz, 2C), 128.54 (s, 2C),
125.52, 126.8 (s, 2C), 84.5 (d, J ) 7.6 Hz), 59.3 (d, J ) 1.9 Hz),
29.9 (d, J ) 8.1 Hz), 14.0 (d, J ) 3.6 Hz). 31P NMR (CDCl3,
121 MHz): δ 132.8 (br q, J ) 87 Hz).
(Sp ,1S,2R)-N-Meth yl-N-(1-h yd r oxy-1-p h en yl)p r op -2-yl-
P -(cycloh exyl)-P -(p h en yl)-p h osp h in a m id e Bor a n e (3c).
Cyclohexyllithium was prepared from chlorocyclohexane and
lithium-naphthalenide.16 Lithium (35 mmol) and naphthalene
(0.35 mmol) were combined in 7 mL of tetrahydrofuran. The
mixture was vigorously stirred at ambient temperature until
it turned dark green, at which point the mixture was cooled
to -78 °C. Chlorocyclohexane was added dropwise via syringe
(3.5 mmol), and the mixture was stirred for 3 h at -78 °C to
generate cyclohexyllithium, which was added to a solution of
2 (1.7 mmol) at -78 °C. Purification: gradient silica gel
chromatography (90:10 hexane/EtOAc, polarity gradually
increased to 50:50 hexane/EtOAc). Yield: 88% (0.57 g, 1.5
mmol), isolated as a white foam. Only one diastereomer was
1
detected by H NMR integration. Rf (80:20 hexane/EtOAc) )
0.24. IR (NaCl): 3495, 2934, 2854, 2382, 1480, 1435, 1023
cm-1. 1H NMR (CDCl3, 500 MHz): δ 7.56-7.52 (m, 2H), 7.43-
7.33 (m, 5H), 7.27-7.18 (m, 3H), 4.74 (d, J ) 4.6 Hz, 1H),
4.09-4.04 (m, 1H), 2.60 (d, J ) 7.0 Hz, 3H), 2.35 (dd, J ) 2.6,
12.4 Hz, 1H), 2.0 (br s, 1H), 2.00-1.88 (m, 1H), 1.75 (m, 3H),
1.58-1.50 (m, 2H), 1.45-1.38 (m, 1H), 1.33-1.23 (m, 3H), 1.12
(d, J ) 7.0 Hz, 3H), 1.1-0.5 (br m, 3H). 13C NMR (CDCl3, 125
MHz): δ 142.7, 131.4 (d, J ) 9.2 Hz), 131.1 (d, J ) 40.1 Hz),
130.7 (d, J ) 1.7 Hz), 128.5 (d, J ) 9.2 Hz), 128.4 (s, 2C), 127.6,
126.3 (s, 2C), 78.8, 58.5 (d, J ) 8.6 Hz), 32.7 (d, J ) 43.7 Hz),
29.5 (d, J ) 3.5 Hz), 27.2 (d, J ) 12.1 Hz), 26.93 (d, J ) 8.6
Hz), 26.86, 26.2, 26.1, 12.4 (d, J ) 4.0 Hz). 31P NMR (CDCl3,
121.5 MHz): δ 72.2 (br q, J ) 66 Hz). HRMS (ESI) [M + Na]+:
m/z calcd for C22H33BNNaOP 392.2285, obsd 392.2290.
Syn th esis of P h osp h in a m id es 3a -h (Typ ica l P r oce-
d u r e). A 1.0 M solution of 2 (20 mmol) in tetrahydrofuran was
cooled to -78 °C before addition of a solution of alkyl- or
aryllithium (40 mmol, commercially available unless noted).
The mixture was allowed to stir for 3 h, warming slowly to 0
°C. Water was added, and the aqueous phase was extracted
with diethyl ether. The combined organic layers were washed
with saturated aqueous NaCl, dried over MgSO4, filtered, and
concentrated in vacuo. The crude residue was purified via
column chromatography.
(Sp ,1S,2R)-N-Meth yl-N-(1-h yd r oxy-1-p h en yl)p r op -2-yl-
P -(2-m et h yl-2-p h en yl-1-p r op yl)-P -(p h en yl)-p h osp h in a -
m id e Bor a n e (3d ). Neophyllithium was prepared from 1-chlo-
ro-2-methyl-2-phenylpropane (neophyl chloride) and lithium-
naphthalenide as described for 3c. Purification: gradient silica
gel chromatography (90:10 hexane/EtOAc, polarity gradually
increased to 50:50 hexane/EtOAc). Yield: 72% (1.53 g, 3.7
mmol), isolated as a white foam. Only one diastereomer was
(Sp,1S,2R)- N-Meth yl-N-(1-h yd r oxy-1-p h en yl)p r op -2-yl-
P -(m eth yl)-P -(p h en yl)-p h osp h in a m id e Bor a n e (3a ).12 Pu-
rification: column chromatography (elution with 95:5 toluene/
EtOAc). Small scale yield: 79% (0.10 g, 0.33 mmol), prepared
and purified for spectral analysis. Large scale crude yield:
>99% (6.0 g, 20 mmol), used without purification. The dia-
stereomeric ratio of the isolated material was determined to
be 9:1 by 1H NMR integration. Mp: 108-109 °C. Rf (95:5
1
detected by H NMR integration. Rf (90:10 hexane/EtOAc) )
0.12. IR (NaCl): 3511, 2968, 2389, 1601, 1496, 1450, 1435
cm-1. 1H NMR (CDCl3, 500 MHz): δ 7.67-7.63 (m, 2H), 7.46-
7.40 (m, 6H), 7.36-7.31 (m, 4H), 7.27-7.21 (m, 3H), 5.12 (br
s, 1H), 4.09-4.07 (m, 1H), 2.70 (t, J ) 16.3 Hz, 1H), 2.65 (d,
J ) 7.0 Hz, 3H), 2.25 (dd, J ) 2.1, 15.3 Hz, 1H), 1.87 (d, J )
2.1 Hz, 1H), 1.67 (s, 3H), 1.64 (s, 3H), 0.95 (d, J ) 7.0 Hz,
3H). 13C NMR (CDCl3, 125 MHz): δ 150.9 (d, J ) 7.5 Hz),
142.8, 135.4 (d, J ) 59.9 Hz), 130.5 (d, J ) 8.6 Hz, 2C), 130.3
(d, J ) 1.7 Hz), 128.7 (d, J ) 9.2 HZ, 2C), 128.4 (d, J ) 4.0
Hz, 2C), 127.4, 126.2, 125.9 (s, 2C), 125.6 (s, 2C), 79.8, 58.2
(d, J ) 10.4 Hz), 41.1 (d, J ) 36.3 Hz), 38.0, 31.2 (d, J ) 5.2
Hz), 31.1 (d, J ) 3.5 Hz), 28.4 (d, J ) 4.6 Hz), 10.4 (d, J ) 5.2
Hz). 31P NMR (CDCl3, 121.5 MHz): δ 67.4 (br q, J ) 53 Hz).
HRMS (ESI) [M + Na]+: m/z calcd for C26H35BNNaOP
442.2442, obsd 442.2464.
1
toluene/EtOAc) ) 0.17. IR (NaCl): 3446, 2968, 2369 cm-1. H
NMR (CDCl3, 500 MHz): δ 7.46-7.26 (m, 8H), 7.11-7.07 (m,
2H), 4.74 (dd, 1H, J ) 3.4, 7.2 Hz), 4.06-4.01 (m, 1H), 2.47
(d, 3H, J ) 8.5 Hz), 1.94 (d, 1H, J ) 3.7 Hz), 1.52 (d, 3H, J )
9.0 Hz), 1.24 (d, 3H, J ) 6.7 Hz), 1.1-0.4 (br m, 3H). 13C NMR
(CDCl3, 125 MHz): δ 143.3, 133.5 (d, J ) 65.6 Hz), 131.3,
131.2, 131.0, 130.9, 129.3, 129.2, 129.1, 129.1, 128.7, 127.5,
78.5 (d, J ) 6.3 Hz), 58.7 (d, J ) 8.6 Hz), 29.7, 14.8, 12.0 (d,
J ) 41.5 Hz). 31P NMR (CDCl3, 121 MHz): δ 66.1 (br q, J )
77 Hz). HRMS (ESI) [M + Na]+: m/z calcd for C17H25BNNaOP
324.1659, obsd 324.1652.
(Rp ,1S,2R)-N-Meth yl-N-(1-h yd r oxy-1-p h en yl)p r op -2-yl-
P -(4-m eth oxyp h en yl)-P -(p h en yl)-p h osp h in a m id e Bor a n e
(3e). A 1.0 M solution of 4-bromoanisole (10 mmol) in diethyl
ether was cooled to -78 °C and treated with a solution of tert-
butyllithium (20 mmol). The solution was allowed to stir 15
min at -78 °C, warmed to 0 °C, and stirred for an additional
30 min producing a clear, yellow solution of p-anisyllithium.
The aryllithium reagent was transferred via cannula to a 1.0
M solution of 2 in tetrahydrofuran (5.0 mmol) at -78 °C. The
mixture was allowed to stir 30 min at -78 °C, warmed to 0 °C
(Sp ,1S,2R)-N-Meth yl-N-(1-h yd r oxy-1-p h en yl)p r op -2-yl-
P -(n -bu tyl)-P -(p h en yl)-p h osp h in a m id e Bor a n e (3b).12 Pu-
rification: column chromatography (95:5 toluene/EtOAc).
Yield: 80% (1.67 g, 4.9 mmol), isolated as a colorless oil. The
diastereomeric ratio of the isolated material was determined
1
to be 16:1 by H NMR integration. Rf (95:5 toluene/EtOAc) )
0.25. IR (thin film): 3503, 2957, 2872, 2379, 1455, 1436, 1025
cm-1. 1H NMR (CDCl3, 500 MHz): δ 7.44-7.42 (m, 2H), 7.36-
7.28 (m, 8H), 4.87 (dd, J ) 3.7, 5.5 Hz, 1H), 4.07-4.02 (m,
1H), 2.57 (d, J ) 7.6 Hz, 3H), 2.00-1.96 (m, 1H), 1.88-1.84
J . Org. Chem, Vol. 68, No. 1, 2003 161

Colby and J amison
to increase the solubility of salts, and stirred for an additional
2 h. Water and diethyl ether were added, and the solution was
warmed to ambient temperature. Purification: gradient silica
gel chromatography (90:10 hexane/EtOAc, polarity gradually
increased to 50:50 hexane/EtOAc). Yield: 80% (1.6 g, 4.0
mmol), isolated as a white solid. Mp: 51-52 °C. Only one
3e. Purification: gradient silica gel chromatography (90:10
hexane/EtOAc, polarity gradually increased to 80:20 hexane/
EtOAc). Yield: 81% (1.8 g, 4.1 mmol). Mp: 110 °C. Rf (80:20
hexane/EtOAc) ) 0.24. IR (thin film): 3566, 3058, 2983, 2366,
1465, 1445, 1436, 1179, 1068, 1026 cm-1. 1H NMR (CDCl3, 500
MHz): δ 7.72-7.68 (m, 2H), 7.51-7.47 (m, 1H), 7.44-7.18 (m,
16H), 4.88-4.87 (m, 1H), 3.97-3.93 (m, 1H), 2.57 (d, J ) 7.3
Hz, 3H), 1.50 (d, J ) 3.1 Hz, 1H), 1.4-0.8 (br m, 3H), 0.69 (d,
J ) 7.0 Hz, 3H). 13C NMR (CDCl3, 125 MHz): δ 147.6 (d, J )
9.8 Hz), 142.7, 141.6 (d, J ) 2.9 Hz), 134.3 (d, J ) 9.8 Hz),
133.6 (d, J ) 58.2 Hz), 132.9 (d, J ) 8.6 Hz), 132.4 (d, J ) 9.8
Hz, 2C), 130.74 (d, J ) 2.3 Hz), 130.70 (d, J ) 2.3 Hz), 129.8,
129.0 (d, J ) 66.2 Hz), 128.4, 128.31 (s, 2C), 128.29, 127.6 (s,
2C), 127.5, 127.3, 127.0 (d, J ) 9.8 Hz), 125.8 (s, 2C), 79.0,
58.2 (d, J ) 10.4 Hz), 32.0 (d, J ) 4.0 Hz), 10.0 (d, J ) 6.9
Hz). 31P NMR (CDCl3, 121.5 MHz): δ 70.1 (br q, J ) 55 Hz).
HRMS (ESI) [M + Na]+: m/z calcd for C28H31BNNaOP
462.2129, obsd 462.2127.
Syn th esis of P h osp h in ite Bor a n es 4a -h (Typ ica l P r o-
ced u r e). Concentrated sulfuric acid (120 mol %) was added
slowly to a solution of phosphinamide borane 3 in methanol
(0.1 M) at ambient temperature. The solution was allowed to
stir 18 h and partitioned between dichloromethane and water,
and the aqueous phase was extracted with dichloromethane.
The combined dichloromethane layers were washed with
saturated aqueous sodium bicarbonate, dried with MgSO4, and
concentrated. The crude residue was purified via column
chromatography (elution with 90:10 hexane/EtOAc) to give
clear, colorless oils (unless otherwise specified).
1
diastereomer was detected by H NMR integration. Rf (80:20
hexane/EtOAc) ) 0.14. IR (thin film): 3457, 2969, 2384, 1596,
1501, 1255 cm-1. 1H NMR (CDCl3, 500 MHz): δ 7.55-7.46 (m,
4H), 7.41-7.25 (m, 6H), 7.14-7.10 (m, 2H), 6.95 (dd, J ) 1.7,
8.7 Hz, 2H), 4.82 (dd, J ) 4.0, 6.3 Hz, 1H), 4.33-4.28 (m, 1H),
3.85 (s, 3H), 2.46 (d, J ) 7.9 Hz, 3H), 1.85 (d, J ) 4.0 Hz, 1H),
1.24 (d, J ) 6.7 Hz, 3H), 1.3-0.7 (br m, 3H). 13C NMR (CDCl3,
125 MHz): δ 162.0, 142.7, 134.5 (d, J ) 11.5 Hz, 2C), 132.1
(d, J ) 9.8 Hz, 2C), 130.7, 128.8 (s, 2C), 128.4 (d J ) 10.9 Hz,
2C), 128.1, 127.0 (s, 2C), 122.0 (d, J ) 63.9 Hz), 114.2 (d, J )
10.9, 2C), 78.9 (d, J ) 6.3 Hz), 58.2 (d, J ) 10.4 Hz), 55.5,
30.4 (d, J ) 4.0 Hz), 13.8. 31P NMR (CDCl3, 121.5 MHz): δ
69.2 (br q, J ) 95 Hz). HRMS (ESI) [M + Na]+: m/z calcd for
C
23H29BNNaO2P 416.1921, obsd 416.1918.
(Rp ,1S,2R)-N-Meth yl-N-(1-h yd r oxy-1-p h en yl)p r op -2-yl-
P -(2-m eth oxyp h en yl)-P -(p h en yl)-p h osp h in a m id e Bor a n e
(3f).9a,10a,b,12 o-Anisyllithium was prepared from the corre-
sponding bromide, and the reaction was carried out as
described for 3e. Purification: gradient silica gel chromatog-
raphy (90:10 hexane/EtOAc, polarity gradually increased to
50:50 hexane/EtOAc). Yield: 93% (1.46 g, 3.7 mmol), isolated
as a white solid. Only one diastereomer was detected by 1H
NMR integration. Mp: 108 °C. Rf (80:20 hexane/EtOAc) ) 0.18.
IR (thin film): 3416, 3060, 2940, 2376, 1589, 1477, 1431, 1276,
(R)-Meth yl-(m eth ylp h en yl)p h osp h in ite Bor a n e (4a ).12
The general procedure was followed, except 3a was used
without purification. Yield over two steps: 75% (2.52 g, 15
mmol). Rf (95:5 hexane/EtOAc) ) 0.42. IR (neat): 3058, 2988,
1
1251 cm-1. H NMR (CDCl3, 500 MHz): δ 7.57 (ddd, J ) 1.8,
7.6, 12.7 Hz), 7.50-7.46 (m, 3H), 7.39-7.23 (m, 8H), 7.03 (tdd,
J ) 0.9, 1.5, 7.5 Hz, 1H), 6.92 (dd, J ) 4.1, 7.8 Hz), 4.91 (d, J
) 5.2 Hz, 1H), 4.37-4.32 (m, 1H), 3.59 (s, 3H), 2.56 (d, J )
7.9 Hz), 1.91 (br s, 1H), 1.23 (d, J ) 7.0 Hz, 3H). 13C NMR
(CDCl3, 125 MHz): δ 135.10 (d, J ) 10.4 Hz), 133.4, 132.4 (d,
J ) 71.4), 131.0 (d, J ) 10.4, 2C), 130.1, 128.5 (s, 2C), 128.1
(d, J ) 10.9, 2C), 127.8, 126.8 (s, 2C), 121.0 (d, J ) 10.9 Hz),
118.7 (d, J ) 57 Hz), 111.7 (d, J ) 4.6 Hz), 79.0 (d, J ) 5.2
Hz), 58.3 (d, J ) 10.4 Hz), 55.2, 31.1 (d, J ) 4.0), 12.7. 31P
NMR (CDCl3, 121.5 MHz): δ 68.5 (br q, J ) 84 Hz). HRMS
(ESI) [M + Na]+: m/z calcd for C23H29BNNaO2P 416.1921, obsd
416.1920.
1
2944, 2842, 2382, 1037 cm-1. H NMR (CDCl3, 500 MHz): δ
7.82-7.78 (m, 2H), 7.58-7.49 (m, 3H), 3.58 (d, 3H, J ) 12.2
Hz), 1.71 (d, 3H, J ) 9.2 Hz), 1.1-0.5 (br m, 3H). 13C NMR
(CDCl3, 125 MHz): δ 132.9 (d, J ) 65.6 Hz), 131.5, 131.4,
129.53, 129.45, 54.4 (d, J ) 2.9 Hz), 16.8 (d, J ) 47.2 Hz). 31P
NMR (CDCl3, 121 MHz): δ 113 (br q, J ) 72 Hz). HRMS (EI)
[M - H+]: m/z calcd for C8H13BOP 167.0792, obsd 167.0794.
(R)-Meth yl-(n -bu tylp h en yl)p h osp h in ite Bor a n e (4b).12
Yield: 62% (0.6 g, 2.9 mmol). Rf (90:10 hexane/EtOAc) ) 0.32.
IR (thin film): 2958, 2872, 2375, 1437, 1033 cm-1 1H NMR
.
(Rp ,1S,2R)-N-Meth yl-N-(1-h yd r oxy-1-p h en yl)p r op -2-yl-
P -(2-m eth ylp h en yl)-P -(p h en yl)-p h osp h in a m id e Bor a n e
(3g).42 o-Tolyllithium was prepared from the corresponding
iodide, and the reaction was carried out as described for 3e.
Purification: gradient silica gel chromatography (90:10 hex-
ane/EtOAc, polarity gradually increased to 50:50 hexane/
EtOAc). Yield: 80% (1.2 g, 3.2 mmol). Only one diastereomer
(CDCl3, 300 MHz): δ 7.79-7.73 (m, 2H), 7.55-7.45 (m, 3H),
3.60 (d, J ) 11.9 Hz, 3H), 2.00-1.86 (m, 2H), 1.52-1.32 (m,
4H), 0.88 (t, J ) 7.2 Hz, 3H), 1.2-0.3 (br m, 3H). 13C NMR
(CDCl3, 125 MHz): δ 132.1 (d, J ) 2.3 Hz), 131.5, 131.1 (d, J
) 10.4 Hz, 2C), 128.9 (d, J ) 9.8 Hz, 2C), 54.0 (d, J ) 2.9 Hz),
30.4 (d, J ) 45.5 Hz), 24.14, 24.11 (d, J ) 13.8 Hz), 13.7. 31P
NMR (CDCl3, 121.5 MHz): δ 116.6 (br q, J ) 72 Hz). HRMS
(ESI) [M + Na]+: m/z calcd for C11H20BNaOP 233.1237, obsd
233.1235.
1
was detected by H NMR integration. Mp: 118 °C. Rf (90:10
hexane/EtOAc) ) 0.09. IR (NaCl, thin film): 3507, 3059, 2979,
2391, 1451, 1436, 1384, 1069, 1024 cm-1. 1H NMR (CDCl3, 500
MHz): δ 7.64-7.60 (m, 2H), 7.51-7.47 (m, 1H), 7.44-7.21 (m,
11H), 4.95 (t, J ) 3.7 Hz, 1H), 4.39-4.35 (m, 1H), 2.65 (d, J )
7.3 Hz, 3H), 2.33 (s, 1H), 1.77 (d, J ) 3.7 Hz, 1H), 1.26 (d, J
) 6.7 Hz, 3H). 13C NMR (CDCl3, 125 MHz): δ 142.7, 142.4 (d,
J ) 12.7 Hz), 132.8 (d, J ) 8.1 Hz), 132.5, 132.4 (d, J ) 9.2
Hz), 132.0 (d, J ) 9.8 Hz, 2C), 131.1 (d, J ) 2.3 Hz), 131.0 (d,
J ) 2.3 Hz), 129.1, 128.6 (d, J ) 10.4 Hz, 2C), 128.4 (s, 2C),
127.6, 126.2 (s, 2C), 125.8 (d, J ) 9.8 Hz), 79.1 (d, J ) 2.3 Hz),
58.2 (d, J ) 9.8 Hz), 31.5 (d, J ) 3.5 Hz), 22.2 (d, J ) 3.5 Hz),
11.7 (d, J ) 4.6 Hz). 31P NMR (CDCl3, 121.5 MHz): δ 69.9 (br
(R)-Meth yl-(cycloh exylph en yl)ph osph in ite Bor an e (4c).
The general procedure was followed, except that the reaction
was heated to 45 °C after addition of sulfuric acid. Yield: 29%
(0.2 g, 0.9 mmol). Rf (90:10 hexane/EtOAc) ) 0.38. IR (NaCl,
thin film): 2933, 2855, 2383, 1728, 1450, 1437, 1114, 1067,
1034, 1003 cm-1. 1H NMR (CDCl3, 500 MHz): δ 7.72-7.68 (m,
2H), 7.54-7.46 (m, 3H), 3.61 (d, J ) 12.1 Hz), 1.93-1.86 (m,
2H), 1.81-1.78 (m, 1H), 1.73 (br s, 1H), 1.66-1.61 (m, 2H),
1.34-1.30 (m, 1H), 1.26-1.13 (m, 4H), 1.1-0.4 (br m, 3H). 13
C
NMR (CDCl3, 125 MHz): δ 131.9 (d, J ) 2.3 Hz), 131.5 (d, J
) 10.4 Hz, 2C), 130.3 (d, J ) 51.2 Hz), 128.7 (d, J ) 9.8 Hz,
2C), 54.3 (d, J ) 3.5 Hz), 39.2 (d, J ) 45.5 Hz), 26.5 (d, J )
4.5 Hz), 26.4 (d, J ) 5.2 Hz), 26.0, 25.6, 25.2. 31P NMR (CDCl3,
121.5 MHz): δ 119.5 (br q, J ) 75 Hz). HRMS (ESI) [M +
Na]+: m/z calcd for C13H22BNaOP 259.1394, obsd 259.1384.
q, J ) 78 Hz). HRMS (ESI) [M + Na]+: m/z calcd for C23H29
BNNaOP 400.1972, obsd 400.1962.
-
(Rp ,1S,2R)-N-Meth yl-N-(1-h yd r oxy-1-p h en yl)p r op -2-yl-
P -(2-b ip h en ylyl)-P -(p h en yl)-p h osp h in a m id e
Bor a n e
(3h ).10b o-Biphenyllithium was prepared from the correspond-
(R)-Meth yl-[(2-m eth yl-2-p h en yl-1-p r op yl)p h en yl]p h os-
p h in ite Bor a n e (4d ). Yield: 65% (0.67 g, 2.3 mmol). Rf (90:
10 hexane/EtOAc) ) 0.29. IR (NaCl): 3058, 2967, 2945, 2384,
ing bromide, and the reaction was carried out as described for
1
1496, 1437, 1065, 1035 cm-1. H NMR (CDCl3, 500 MHz): δ
(42) Moulin, D.; Bago, S.; Bauduin, C.; Darcel, C.; J uge´, S. Tetra-
hedron: Asymmetry 2000, 11, 3939-3956.
7.62-7.58 (m, 2H), 7.47-7.44 (m, 1H), 7.40-7.7.37 (m, 2H),
162 J . Org. Chem., Vol. 68, No. 1, 2003

P-Chiral, Monodentate Ferrocenyl Phosphines
7.31-7.29 (m, 2H), 7.24-7.21 (m, 2H), 7.16-7.13 (m, 1H), 3.42
(d, J ) 11.9 Hz, 3H), 2.51 (t, J ) 14.8 Hz, 1H), 2.31 (dd, J )
5.2, 15.2 Hz, 1H), 1.55 (s, 3H), 1.50 (s, 3H), 1.2-0.5 (br m,
3H). 13C NMR (CDCl3, 125 MHz): δ 148.6, 133.1 (d, J ) 55.8
Hz), 131.6 (d, J ) 2.9 Hz), 130.6 (d, J ) 10.4 Hz, 2C), 128.7
(d, J ) 9.8 Hz, 2C), 128.2 (s, 2C), 126.1, 125.8 (s, 2C), 53.7,
47.3 (d, J ) 38.6 Hz), 37.7, 30.4 (d, J ) 5.2 Hz), 30.2 (d, J )
5.8 Hz). 31P NMR (CDCl3, 121.5 MHz): δ 114.5 (br q, J ) 69
Hz). HRMS (ESI) [M + Na]+: m/z calcd for C17H24BNaOP
309.1550, obsd 309.1551.
(S)-Meth yl-[(4-m eth oxyph en yl)ph en yl]ph osph in ite Bo-
r a n e (4e). Yield: 77% (0.7 g, 2.7 mmol). Rf (80:20 hexane/
EtOAc) ) 0.31. IR (thin film): 3059, 3008, 2944, 2840, 2383,
1595, 1503 cm-1. 1H NMR (CDCl3, 500 MHz): δ 7.74-7.67 (m,
4H), 7.52-7.45 (m, 3H), 7.0-6.96 (m, 2H), 3.85 (s, 3H), 3.72
(d, J ) 12.2 Hz, 3H), 1.3-0.7 (br m, 3H). 13C NMR (CDCl3,
125 MHz): δ 162.6 (d, J ) 2.2 Hz), 133.5 (d, J ) 12.6, 2C),
131.8 (d, J ) 2.4 Hz), 132.1 (d, J ) 65.6 Hz), 131.1 (d, J )
11.2 Hz, 2C), 128.7 (d, J ) 10.5 Hz, 2C), 122.3 (d, J ) 67.7
Hz), 114.4 (d, J ) 11.4 Hz), 55.6, 54.1. 31P NMR (CDCl3, 121.5
MHz): δ 105.9 (br q, J ) 76 Hz). HRMS (ESI) [M + Na]+:
m/z calcd for C14H18BNNaO2P 283.1030, obsd 283.1024.
to 0 °C and stirred for an additional 15 min to generate FcLi.
A 1.0 M solution of 4 (4 mmol) in THF was cooled to -78 °C,
and the FcLi solution was transferred to it via cannula over
10 min. The solution was allowed to warm to ambient
temperature and stirred for 14 h. Water was added, and the
aqueous phase was extracted with diethyl ether. The combined
organic layers were washed with saturated aqueous NaCl,
dried with MgSO4, filtered, and concentrated in vacuo. The
crude residue was purified via gradient column chromatogra-
phy (elution with 80:20 hexane/CH2Cl2, polarity gradually
increased to 50:50).
(S)-F er r ocen ylm et h ylp h en ylp h osp h in e Bor a n e (5a ).
Yield: 58% (0.75 g, 2.3 mmol), isolated as an orange oil that
was crystallized from hexane. Enantiomeric excess: 83% ee
by HPLC analysis (Chiracel OJ , isocratic, hexane/2-propanol
95:5, tR [(R)-5a ] ) 16.8 min, tR [(S)-5a ] ) 24.7 min). Mp: 73-
74 °C. Rf (1:1 hexane/CH2Cl2) ) 0.35. IR (thin film): 3096,
2919, 2379 cm-1. 1H NMR (CDCl3, 500 MHz): δ 7.67-7.63 (m,
2H), 7.44-7.40 (m, 3H), 4.51-4.48 (m, 3H), 4.45 (m, 1H), 4.29-
4.28 (s, 5H), 1.80 (d, 3H, J ) 10.4 Hz), 1.2-0.7(br m, 3H). 13C
NMR (CDCl3, 125 MHz): δ 133.1 (d, J ) 56 Hz), 131.8 (d, 2C,
J ) 6.3 Hz), 131.5 (d, 1C, J ) 2.8 Hz), 129.3 (d, 2C, J ) 13.8
Hz), 72.5 (d, 1C, J ) 8.6 Hz), 72.2 (d, 1C, J ) 6.9 Hz), 71.1 (d,
1C, J ) 6.3 Hz), 70.5 (5C), 13.9 (d, J ) 42 Hz). 31P NMR δ
(S)-Meth yl-[(2-m eth oxyph en yl)ph en yl]ph osph in ite Bo-
r a n e (4f).9a,10a,b,12 Yield: 76% (0.53 g, 2.0 mmol). Rf (10:90
hexane/EtOAc) ) 0.18. IR (thin film): 3060, 2943, 2840, 2382,
(CDCl3, 121 MHz): 6.2 (br q, J ) 76 Hz). [R]20 ) -32.3 (c
D
1590, 1478, 1432, 1278, 1252, 1064, 1033 cm-1 1H NMR
.
0.60; CH2Cl2). HRMS (EI): m/z calcd for C17H20BFeP 322.0740,
obsd 322.0750.
(CDCl3, 500 MHz): δ 7.81 (ddd, J ) 1.7, 7.6, 12.4, 1H) 7.77-
7.73 (m, 2H), 7.53-7.47 (m, 2H), 7.45-7.42 (m, 2H), 7.08 (tdd,
J ) 0.9, 1.8, 7.5, 1H), 6.88 (dd, J ) 4.3, 8.2 Hz, 1H), 3.75 (d,
J ) 12.2 Hz, 3H), 3.64 (s, 3H), 1.3-0.7 (br m, 3H). 13C NMR
(CDCl3, 125 MHz): δ 161.2 (d, J ) 3.5 Hz), 134.13 (d, J ) 1.7
Hz), 134.13 (d, J ) 10.9 Hz), 132.2 (d, J ) 66.2 Hz), 131.5 (d,
J ) 2.3 Hz), 131.3 (d, J ) 11.5 Hz, 2C), 128.3 (d, J ) 10.9 Hz,
2C), 121.0 (d, J ) 10.9 Hz), 119.5 (d, J ) 63.3 Hz), 111.8 (d, J
) 5.2 Hz), 55.7, 54.1 (d,J ) 2.9 Hz). 31P NMR (CDCl3, 121.5
MHz): δ 105.8 (br q, J ) 76 Hz). HRMS (ESI) [M + Na]+:
m/z calcd for C14H18BNNaO2P 283.1030, obsd 283.1026.
(S)-n -Bu t ylfer r ocen ylp h en ylp h osp h in e Bor a n e (5b ).
Yield: 90% (0.7 g, 1.8 mmol), isolated as an orange oil.
Enantiomeric excess: 77% ee by HPLC analysis (Chiracel OJ ,
isocratic, hexane/2-propanol 97.5:2.5, tR [(R)-5b] ) 10.0 min,
tR [(S)-5b] ) 12.0 min). Rf (50:50 hexane/CH2Cl2) ) 0.36. IR
(NaCl): 3386, 3097, 2957, 2870, 2380, 1436, 1172, 1107, 1065
cm-1. 1H NMR (CDCl3, 500 MHz): δ 7.79-7.75 (m, 2H), 7.49-
7.44 (m, 3H), 4.56-4.55 (m, 1H), 4.47-4.46 (m, 1H), 4.44-
4.42 (m, 1H), 4.37-4.36 (m, 1H), 4.18 (s, 5H), 2.09-2.03 (m,
2H), 1.60-1.57 (m, 1H), 1.40-1.30 (m, 3H), 0.88 (t, J ) 7.2
Hz, 3H), 1.3-0.7 (br m, 3H). 13C NMR (CDCl3, 125 MHz): δ
132.2 (d, J ) 8.6 Hz, 2C), 131.1 (d, J ) 2.3 Hz), 130.6 (d, J )
2.9 Hz), 128.7 (d, J ) 9.8 Hz, 2C), 71.9 (d, J ) 9.8 Hz), 71.8 (d,
J ) 3.5 Hz), 71.7, 71.3 (d, J ) 7.5 Hz), 69.9 (s, 5C), 27.7 (d, J
) 39.1 Hz), 25.5, 24.5 (d, J ) 14.4 Hz), 13.8. 31P NMR (CDCl3,
(S)-Meth yl-[(2-m eth ylp h en yl)p h en yl]p h osp h in ite Bo-
r a n e (4g). Yield: 87% (0.62 g, 2.5 mmol). Rf (10:90 hexane/
EtOAc) ) 0.37. IR (thin film): 3058, 2944, 2385, 1438, 1137,
1
1067, 1033 cm-1. H NMR (CDCl3, 500 MHz): δ 7.90 (dd, J )
7.6, 12.8, 1H, 7.68-7.64 (m, 2H), 7.54-7.51 (m, 1H), 7.47-
7.44 (m, 3H), 7.34 (t, J ) 7.3, 1H), 6.22 (dd, J ) 3.7, 7.3 Hz,
1H), 3.76 (d, J ) 12.2 Hz, 3H), 2.25 (s, 3H), 1.3-0.7 (br m,
3H). 13C NMR (CDCl3, 125 MHz): δ 142.1 (d, J ) 8.1 Hz), 133.9
(d, J ) 15.0 Hz), 132.5 (d, J ) 2.3 Hz), 132.0 (d, J ) 64.5 Hz),
131.9 (d, J ) 2.3 Hz), 131.8 (d, J ) 8.6 Hz), 131.4 (d, J ) 11.5,
2C Hz), 129.2 (d, J ) 60.4 Hz), 128.8 (d, J ) 10.4 Hz, 2C),
125.9 (d, J ) 11.5 Hz), 54.0, 21.4 (d, J ) 4.0 Hz). 31P NMR
(CDCl3, 121.5 MHz): δ 109.5 (br q, J ) 72 Hz). HRMS (ESI)
[M + Na]+: m/z calcd for C14H18BNaOP 267.1081, obsd
267.1089.
121.5 MHz): δ 11.9 (br q, J ) 75 Hz). [R]20 ) -48.4 (c 1.10;
D
CH2Cl2). HRMS (EI): m/z calcd for C20H26BFeP 364.1209, obsd
364.1194.
(S)-Cycloh exylfer r ocen ylph en ylph osph in e Bor an e (5c).
Yield: 66% (1.0 g, 2.6 mmol), isolated as an orange solid.
Enantiomeric excess: 97% ee by chiral HPLC analysis (Chiracel
OJ , isocratic, hexane/2-propanol 97.5:2.5, tR [(R)-5c] ) 8.3 min,
tR [(S)-5c] ) 10.0 min). Rf (50:50 hexane/CH2Cl2) ) 0.33. Mp:
95-96 °C. IR (NaCl): 2931, 2854, 2381 cm-1. 1H NMR (CDCl3,
500 MHz): δ 7.95-7.91 (m, 2H), 7.54-7.53 (m, 3H), 4.66 (br
s, 1H), 4.43 (br s, 1H), 4.40 (br s, 1H), 4.24 (br s, 1H), 3.97 (s,
5H), 2.03 (dd, J ) 12.4, 26 Hz, 1H), 1.77-1.76 (m, 1H), 1.70-
1.62 (m, 3H), 1.44-1.23 (m, 3H), 1.20-1.12 (m, 3H), 1.1-0.6
(br m, 3H). 13C NMR (CDCl3, 125 MHz): δ 132.8 (d, J ) 8.6
Hz, 2C), 131.3 (d, J ) 2.9 Hz), 129.3 (d, J ) 55.9 Hz), 128.7
(d, J ) 9.2 Hz, 2C), 74.6 (d, J ) 15.0 Hz), 71.8 (d, J ) 6.3 Hz),
70.9 (d, J ) 8.6 Hz), 70.6 (d, J ) 4.0 Hz), 69.8 (s, 5C), 69.2 (d,
J ) 62.8 Hz), 37.2 (d, J ) 37.4 Hz), 27.1, 26.9 (d, J ) 4.6 Hz),
26.9 (d, J ) 19.6 Hz), 26.7, 26.0 (d, J ) 1.2 Hz). 31P NMR
(CDCl3, 121.5 MHz): δ 19.3 (br q, J ) 67 Hz). [R]20D ) -281.8
(c 0.55; CH2Cl2). HRMS (EI): m/z calcd for C22H28BFeP
390.1366, obsd 390.1351.
(S)-Meth yl-[(2-bip h en ylyl)p h en yl]p h osp h in ite Bor a n e
(4h ).10b Yield: 77% (0.95 g, 3.1 mmol), isolated as a white solid.
Mp: 62-63 °C. Rf (90:10 hexane/EtOAc) ) 0.34. IR (thin
film): 3056, 2943, 2383, 1465, 1438, 1131, 1114, 1064, 1033
cm-1. 1H NMR (CDCl3, 500 MHz): δ 8.10-8.06 (m, 1H), 7.57-
7.50 (m, 2H), 7.39-7.31 (m, 3H), 7.27-7.21 (m, 4H), 7.14-
7.11 (m, 2H), 6.94-6.92 (m, 2H), 3.58 (d, J ) 12.2 Hz, 3H),
1.2-0.8 (br m, 3H). 13C NMR (CDCl3, 125 MHz): δ 146.8 (d, J
) 7.5 Hz), 140.5 (d, J ) 2.9 Hz), 133.7 (d, J ) 5.0 Hz), 132.4
(d, J ) 67.3 Hz), 131.8 (d, J ) 7.4 Hz), 131.7 (d, J ) 2.3 Hz),
131.3 (d, J ) 2.3 Hz), 131.1 (d, J ) 10.9 Hz, 2C), 130.3 (d, J )
60.4 Hz), 129.7 (s, 2C), 128.3 (d, J ) 10.9 Hz, 2C), 127.4, 127.35
(s, 2C), 127.2 (d, J ) 11.5 Hz), 53.8. 31P NMR (CDCl3, 121.5
MHz): δ 108.6 (br q, J ) 69 Hz). HRMS (ESI) [M + Na]+:
m/z calcd for C19H20BNaOP 329.1237, obsd 329.1251.
(S)-Fer r ocen ylph en yl(2-m eth yl-2-ph en yl-1-pr opyl)ph os-
p h in e Bor a n e (5d ). Yield: 79% (0.66 g, 1.5 mmol), isolated
as an orange oil. Enantiomeric excess: 98% ee by chiral HPLC
analysis (Chiracel AD, isocratic, hexane/2-propanol 98:2, tR
[(R)-5d ] ) 7.3 min, tR [(S)-5d ] ) 7.8 min). Rf (80:20 hexane/
CH2Cl2) ) 0.06. IR (NaCl): 3088, 3057, 2965, 2389, 1496, 1437,
Syn th esis of P h osp h in e Bor a n es 5a -h (Typ ica l P r o-
ced u r e). A 0.075 M solution of bromoferrocene (8 mmol) in
diethyl ether was prepared and cooled to -78 °C. tert-
Butyllithium (16 mmol) was slowly added, and the solution
was stirred for 10 min at -78 °C. The solution was warmed
1
1387, 1171, 1107, 1063 cm-1. H NMR (CDCl3, 500 MHz): δ
7.74-7.70 (m, 2H), 7.41-7.40 (m, 1H), 7.36-7.33 (m, 2H),
J . Org. Chem, Vol. 68, No. 1, 2003 163

Colby and J amison
7.26-7.24 (m, 2H), 7.20-7.16 (m, 2H), 7.13-7.11 (m, 1H),
4.55-4.54 (m, 1H), 4.41-4.40 (m, 1H), 4.37 (m, 2H), 4.10 (s,
5H), 2.72 (t, J ) 14.2 Hz, 1H), 2.63 (dd, J ) 9.2, 14.6 Hz, 1H),
1.54 (s, 3H), 1.43 (s, 3H). 13C NMR (CDCl3, 125 MHz): δ 148.8
(d, J ) 6.9 Hz), 132.0 (d, J ) 11.4 Hz, 2C), 131.6, 130.7 (d, J
) 2.3 Hz), 128.4 (d, J ) 9.8 Hz, 2C), 128.2 (s, 2C), 126.1, 125.7
(s, 2C), 72.6 (d, J ) 66.2 Hz), 71.9 (d, J ) 10.4 Hz), 71.6 (d, J
) 7.5 Hz), 71.5 (d, J ) 9.2 Hz), 70.9 (d, J ) 7.5 Hz), 69.8 (s,
5C), 43.6 (d, J ) 32.2 Hz), 38.3, 31.0 (d, J ) 5.2 Hz), 29.2 (d,
J ) 4.6 Hz). 31P NMR (CDCl3, 121.5 MHz): δ 6.3 (br q, J ) 70
1H), 7.13-7.10 (m, 1H), 7.04-7.01 (m, 2H), 6.94 (br s, 2H),
4.75 (br s, 1H), 4.49 (br s, 1H), 4.43 (br s, 1H), 4.10 (br s, 1H),
3.90 (s, 5H). 13C NMR (CDCl3, 125 MHz): δ 146.7 (d, J ) 9.2
Hz), 140.5 (d, J ) 3.5 Hz), 133.5 (d, J ) 8.6 Hz), 133.0 (d, J )
9.2 Hz, 2C), 131.80 (d, J ) 8.1 Hz), 131.79, 131.3 (d, J ) 18.4
Hz), 130.9 (d, J ) 2.3 Hz), 130.7, 130.15, 130.1 (d, J ) 2.3
Hz), 128.1 (d, J ) 10.4 Hz, 2C), 127.1 (s, 2C), 127.0, 126.9 (d,
J ) 9.2 Hz). 31P NMR (CDCl3, 121 MHz): δ 18.1 (br s). [R]20
D
) -180.8 (c 0.40; CH2Cl2). HRMS (ESI) [M + Na]+: m/z calcd
for C28H26BFeNaP 483.1107, obsd 483.1107.
Hz). [R]20 ) -72.3 (c 0.90; CH2Cl2). HRMS (ESI) [M + Na]+:
D
Syn th esis of P h osp h in es 1a -h (Typ ica l P r oced u r e).
Diethylamine was degassed, and a 0.1 M solution of 5 was
prepared (1 mmol in 10 mL diethylamine). The solution was
heated at reflux 14 h and cooled to ambient temperature, and
the diethylamine was removed by evaporation under reduced
pressure. The crude orange residue was taken up in a solution
of 95:5 hexane/EtOAc (degassed) and passed through a short
column of silica gel eluting, under argon, with 95:5 hexane/
EtOAc (also degassed) to yield an orange solid (unless other-
wise noted). The enantiomeric excess was determined by
reprotection with BH3‚THF and analysis by chiral HPLC.
m/z calcd for C26H30BFeNaP 463.1420, obsd 463.1418.
(R)-Fer r ocen yl(4-m eth oxyph en yl)ph en ylph osph in e Bo-
r a n e (5e). Yield: 85% (0.56 g, 1.4 mmol), isolated as an orange
oil. Enantiomeric excess: 95% ee by chiral HPLC analysis
(Chiracel OJ , isocratic, hexane/2-propanol 90:10, tR [(S)-5e] )
22.8 min, tR [(R)-5e] ) 30.3 min). Rf (50:50 hexane/CH2Cl2) )
0.30. IR (thin film): 3056, 2960, 2838, 2384, 1596, 1570, 1501,
1293, 1256, 1181, 1109, 1062 cm-1 1H NMR (CDCl3, 500
.
MHz): δ 7.58-7.53 (m, 4H), 7.45-7.43 (m, 1H), 7.41-7.38 (m,
2H), 6.95 (dd, J ) 1.8, 8.9 Hz, 2H), 4.52-4.50 (m, 2H), 4.46-
4.45 (m, 1H), 4.37 (m, 1H), 4.13 (s, 5H), 3.84 (s, 3H). 13C NMR
(CDCl3, 125 MHz): δ 161.9, 134.6 (d, J ) 10.9 Hz, 2C), 132.5
(d, J ) 9.2 Hz, 2C), 132.2 (d, J ) 59.9 Hz), 130.8, 128.5 (d, J
) 9.8 Hz, 2C), 121.9 (d, J ) 64.5 Hz), 114.2 (d, J ) 10.9 Hz,
2C), 73.1 (d, J ) 10.9 Hz), 72.6 (d, J ) 9.2 Hz), 72.0, 71.9,
71.84, 69.9 (s, 5C), 55.5. 31P NMR (CDCl3, 121.5 MHz): δ 14.8
(S)-Fer r ocen ylm eth ylph en ylph osph in e (1a). Yield: 93%
(0.343 g, 1.1 mmol). Enantiomeric excess: 87% ee determined
by chiral HPLC (Chiracel OJ , isocratic, hexane/2-propanol 95:
5, tR [(R)-5a ] ) 16.8 min, tR [(S)-5a ] ) 24.7 min). Recrystal-
lization from hexane (90% yield) provided 1a in 96% ee. Rf
(95:5 hexane/EtOAc) ) 0.42. Mp: 84-85 °C. 1H NMR (CDCl3,
300 MHz): δ 7.40-7.34 (m, 3H), 7.31-7.25 (m, 2H), 4.39-
4.30 (m, 4H), 4.22-4.21 (s, 5H), 1.64 (d, 3H, J ) 3.0 Hz). 13C
NMR (CDCl3, 125 MHz): δ 131.3 (d, J ) 18.4 Hz, 2C), 130.2
(d, J ) 9.2 Hz), 128.5 (d, J ) 11.5 Hz), 128.3 (d, J ) 6.7 Hz,
2C), 74.5 (d, J ) 28.5 Hz), 71.2, 69.8, 12.6 (d, J ) 8.1 Hz). 31P
NMR (CDCl3, 121 MHz): δ -37.4. HRMS (EI): m/z calcd for
(br q, J ) 65 Hz). [R]20 ) +20.0 (c 0.25; CH2Cl2). HRMS (EI):
D
m/z calcd for C23H24BFeOP 414.1002, obsd 414.0999.
(R)-Fer r ocen yl(2-m eth oxyph en yl)ph en ylph osph in e Bo-
r a n e (5f).9a Yield: 92% (0.38 g, 0.9 mmol). Enantiomeric
excess: >98% ee by chiral HPLC analysis (Chiracel OJ ,
isocratic, hexane/2-propanol 99:1, tR [(R)-5f] ) 43.8 min, tR [(S)-
5f] ) 56.9 min). Rf (90:10 hexane/EtOAc) ) 0.18. Mp: 140 °C.
IR (thin film): 3434, 3074, 2938, 2382, 1736, 1589, 1574, 1478,
1432, 1277, 1251, 1170, 1107, 1061 cm-1. 1H NMR (CDCl3, 500
MHz): δ 7.82-7.77 (m, 1H), 7.55-7.48 (m, 3H), 7.40-7.33 (m,
3H), 7.09-7.06 (m, 1H), 6.89 (dd, J ) 3.8, 8.1 Hz, 1H), 4.70-
4.69 (m, 1H), 4.54 (br s, 1H), 4.51-4.49 (m, 2H), 4.04 (s, 5H),
3.47 (s, 3H). 13C NMR (CDCl3, 125 MHz): δ 135.6, 133.5, 131.5
(d, J ) 9.8 Hz, 2C), 130.1, 128.0 (d, J ) 10.9 Hz, 2C), 121.0 (d,
J ) 10.9 Hz, 1C), 112.0, 74.1 (d, J ) 12.1 Hz), 73.6 (d, J ) 8.6
Hz), 71.8 (d, J ) 7.5 Hz), 71.6 (d, J ) 8.1 Hz), 69.9 (s, 5C),
55.5.31P NMR (CDCl3, 121 MHz): δ 14.1 (br q, J ) 55 Hz).
C
17H17FeP 308.0412, obsd 308.0422.
(S)-n -Bu tylfer r ocen ylph en ylph osph in e (1b). Yield: 88%
(0.35 g, 1 mmol), isolated as an orange oil. Enantiomeric
excess: 80% ee determined by chiral HPLC (Chiracel OJ ,
isocratic, hexane/2-propanol 97.5:2.5, tR [(R)-5b] ) 10.0 min,
tR [(S)-5b] ) 12.0 min). Rf (90:10 hexane/EtOAc) ) 0.48. 1H
NMR (CDCl3, 500 MHz): δ 7.53-7.50 (m, 2H), 7.34-7.33 (m,
3H), 4.40-4.38 (m, 2H), 4.33 (br s, 1H), 4.18 (br s, 1H), 4.16
(s, 5H), 2.03-1.96 (m, 2H), 1.55-1.40 (m, 4H), 0.92 (t, J ) 7.0
Hz, 3H). 13C NMR (CDCl3, 125 MHz): δ 140.2 (d, J ) 13.8
Hz), 132.8 (d, J ) 19.6 Hz, 2C), 128.7, 128.2 (d, J ) 6.9 Hz,
2C), 77.6 (d, J ) 8.1 Hz), 73.2 (d, J ) 20.1 Hz), 70.7 (d, J )
4.6 Hz), 70.4 (d, J ) 8.1 Hz), 70.1 (d, J ) 2.3 Hz), 69.2 (s, 5C),
28.8 (d, J ) 11.5 Hz), 28.7 (d, J ) 2.3 Hz), 24.5 (d, J ) 13.2
Hz), 14.0. 31P NMR (CDCl3, 121.5 MHz): δ -27.1 (br s). HRMS
(EI): m/z calcd for C20H23FeP 350.0881, obsd 350.0880.
[R]20 ) +60.0 (c 0.25; CH2Cl2). HRMS (EI): m/z calcd for
D
C
23H24BFeOP 414.1002, obsd 414.1004.
(R)-F er r ocen yl(2-m eth ylp h en yl)p h en ylp h osp h in e Bo-
r a n e (5g). Yield: 70% (0.50 g, 1.3 mmol). Enantiomeric
excess: 83% ee by chiral HPLC analysis (Chiracel OJ , isocratic,
hexane/2-propanol 99:1, tR [(R)-5g] ) 14.0 min, tR [(S)-5g] )
20.3 min). Rf (80:20 hexane/EtOAc) ) 0.50. Mp: 168-169 °C.
(S )-Cycloh e xylfe r r oce n ylp h e n ylp h osp h in e
(1c).
Yield: 84% (0.35 g, 0.9 mmol). Enantiomeric excess: 98% ee
by chiral HPLC (Chiracel OJ , isocratic, hexane/2-propanol
97.5:2.5, tR [(R)-5c] ) 8.3 min, tR [(S)-5c] ) 10.0 min). Mp:
99-101 °C. 1H NMR (CDCl3, 500 MHz): δ 7.67-7.63 (m, 2H),
7.42-7.39 (m, 3H), 4.37-4.36 (m, 1H), 4.34-4.43 (m, 1H)
4.28-4.26 (m, 1H), 4.03-4.02 (m, 1H), 4.00 (s, 5H), 1.96-1.93
(m, 1H), 1.86-1.84 (m, 1H), 1.79-1.78 (m, 1H), 1.68-1.66 (m,
2H), 1.48-1.45 (m, 1H), 1.29-1.17 (m, 4H), 1.09-1.05 (m, 1H).
13C NMR (CDCl3, 125 MHz): δ 137.4 (d, J ) 10.9 Hz), 134.5
(d, J ) 20.7 Hz, 2C), 129.2, 128.2 (d, J ) 8.1 Hz, 2C), 76.6 (d,
J ) 11.5 Hz), 74.1 (d, J ) 24.8 Hz), 71.1 (d, J ) 2.9 Hz), 70.5
(d, J ) 1.7 Hz), 70.0 (d, J ) 6.3 Hz), 69.2 (s, 5C), 38.1 (d, J )
6.3 Hz), 30.3, 30.2, 27.0 (d, J ) 12.1 Hz), 26.9, 26.6. 31P NMR
(CDCl3, 121.5 MHz): δ -12.0. HRMS (EI): m/z calcd for
IR (thin film): 3055, 2393, 1437, 1171, 1107, 1063 cm-1 1H
.
NMR (CDCl3, 500 MHz): δ 7.80-7.76 (m, 2H), 7.58-7.54 (m,
1H), 7.52-7.49 (m, 2H), 7.33-7.11 (m, 2H), 7.08-7.04 (m, 1H),
4.77-4.76 (m, 1H), 4.59-4.58 (m, 1H), 4.50-4.49 (m, 1H),
4.08-4.07 (m, 1H), 4.07 (s, 5H), 2.09 (s, 3H). 13C NMR (CDCl3,
125 MHz): δ 141.8 (d, J ) 10.4 Hz), 133.4 (d, J ) 8.1 Hz),
132.8 (d, J ) 9.8 Hz, 2C), 131.7 (d, J ) 9.2 Hz), 131.3, 130.9,
130.8, 130.4 (d, J ) 16.1 Hz), 128.8 (d, J ) 9.8 Hz, 2C), 125.7
(d, J ) 9.8 Hz), 72.2 (d, J ) 6.3 Hz), 72.0 (d, J ) 10.4 Hz),
71.8, 70.1 (d, J ) 70.2 Hz), 70.0 (s, 5C), 22.2 (d, J ) 4.6 Hz).
31P NMR (CDCl3, 121 MHz): δ 17.1 (br q, J ) 60 Hz). [R]20
)
D
-269.3 (c 0.15; CH2Cl2). HRMS (ESI) [M + Na]+: m/z calcd
for C23H24BFeNaP 421.0950, obsd 421.0952.
C
22H25FeP 376.1038, obsd 376.1030.
(R)-Fer r ocen yl(2-bip h en ylyl)p h en ylp h osp h in e Bor a n e
(5h ). Yield: 69% (0.54 g, 1.2 mmol). Enantiomeric excess: 98%
ee by chiral HPLC analysis (Chiracel AD, isocratic, hexane/
2-propanol 99.4:0.6, tR [(R)-5h ] ) 13.2 min, tR [(S)-5h ] ) 14.3
min). Rf (50:50 hexane/CH2Cl2) ) 0.34. M.p. 135-137 °C. IR
(S)-Fer r ocen ylph en yl(2-m eth yl-2-ph en yl-1-pr opyl)ph os-
p h in e (1d ). Yield: >99% (0.40 g, 0.94 mmol), isolated as an
orange oil. Enantiomeric excess: 96% ee by chiral HPLC
analysis (Chiracel AD, isocratic, hexane/2-propanol 98:2, tR
[(R)-5d ] ) 7.3 min, tR [(S)-5d ] ) 7.8 min). Rf (90:10 hexane/
(thin film): 3055, 2385, 1464, 1438, 1169, 1108, 1060 cm-1
.
1H NMR (CDCl3, 500 MHz): δ 7.64-7.60 (m, 2H), 7.46-7.40
(m, 2H), 7.36-7.33 (m, 2H), 7.31-7.26 (m, 2H), 7.18-7.15 (m,
EtOAc) ) 0.47. H NMR (CDCl3, 500 MHz): δ 7.46-7.43 (m,
1
2H), 7.35-7.33 (m, 2H), 7.27-7.23 (m, 5H), 7.17-7.16 (m, 1H),
164 J . Org. Chem., Vol. 68, No. 1, 2003

P-Chiral, Monodentate Ferrocenyl Phosphines
4.28-4.27 (m, 1H), 4.25-4.23 (m, 2H), 4.09-4.06 (m, 1H), 4.05
(s, 5H), 2.57 (dd, J ) 6.3, 13.9 Hz, 1H), 2.43 (d, J ) 13.7 Hz,
1H), 1.46 (s, 3H), 1.43 (s, 3H).13C NMR (CDCl3, 125 MHz): δ
145.5 (d, J ) 3.4 Hz), 133.6 (d, J ) 21.3 Hz, 2C), 128.8, 128.2
(d, J ) 7.5 Hz, 2C), 128.0 (d, J ) 1.2 Hz, 2C), 126.0, 72.8 (d,
J ) 19.0 Hz), 70.9 (d, J ) 11.5 Hz), 70.6 (d, J ) 5.2 Hz), 70.0
(d, J ) 2.9 Hz), 69.1 (s, 5C), 46.3 (d, J ) 12.1 Hz), 38.2 (d, J
) 15.5 Hz), 30.3, 30.2. 31P NMR (CDCl3, 121.5 MHz): δ -36.3.
HRMS (EI): m/z calcd for C26H27FeP 426.1194, obsd 426.1197.
Syn th esis of Allylic Alcoh ols 6a ,b, 7-9, 10a ,b (Typ ica l
P r oced u r e). In a glovebox, Ni(cod)2 (14 mg, 0.05 mmol) and
solid ligand (0.05 mmol) were placed into a flask, which was
then sealed with a rubber septum and removed from the
glovebox. If a liquid phosphine was employed, it was added
via syringe immediately after removal from the glovebox. A
2.0 M solution of Et3B in EtOAc was added (0.5 mL, 1.0 mmol),
and the mixture was stirred for 10 min at ambient tempera-
ture. The aldehyde (1.0 mmol) and alkyne (0.5 mmol) were
added via syringe in succession, and the reaction was stirred
for 14 h at ambient temperature. After this time, the solution
was allowed to stir open to the air for 1 h. The solvent was
evaporated, and the crude residue was purified via gradient
column chromatography (50:1 hexanes/EtOAc, polarity gradu-
ally increased to 9:1) to afford the desired alcohol as a clear,
colorless oil. The enantiomeric excess of 6a ,b, 7-9, and 10a ,b
was determined by chiral GC or chiral HPLC analysis.
(E)-1-Cycloh exyl-2,4-d im eth yl-p en t-1-en -3-ol (6a ) a n d
(E)-4-Cycloh exyl-2-m eth yl-h ex-4-en -3-ol (6b). Enantiomer-
ic excess determined by chiral GC analysis (B-PH, isothermal,
140 °C, tR [(R)-6b] ) 6.85 min, tR [(S)-6b] ) 7.04 min, tR [(R)-
6a ] ) 9.36 min, tR [(S)-6a ] ) 9.64 min). IR (thin film): 3383,
2925, 2852, 1448, 1010 cm-1. Rf (90:10 hexane/EtOAc) ) 0.38.
1H NMR (CDCl3, 500 MHz): δ 5.46 (q, 1H, 6b, J ) 7.0 Hz),
5.18 (d, 1H, 6a , J ) 9.2 Hz), 3.65 (d, 1H, 6b, J ) 7.6 Hz), 3.29
(d, 1H, 6a , J ) 8.2 Hz), 2.34-2.28 (m, 1H, 6b), 2.23-2.16 (m,
1H, 6a ), 1.87-0.99 (m, 18H, 6a , 6b), 0.83 (d, 1H, 6b, J ) 6.7
Hz), 0.77 (d, 1H, 6a , J ) 6.7 Hz). 13C NMR (CDCl3, 125 MHz):
δ 146.7, 134.6, 134.1, 120.6, 84.4, 80.0, 39.1, 36.7, 33.2, 32.2,
31.6, 31.3, 31.2, 27.20, 27.19, 26.4, 26.3, 26.17, 26.14, 20.5, 19.6,
18.9, 18.2, 13.7, 11.4. HRMS (ESI) [M + Na]+: m/z calcd for
(R)-F er r ocen yl(4-m et h oxyp h en yl)p h en ylp h osp h in e
(1e). Yield: 95% (86 mg, 0.21 mmol), isolated as an orange
oil. Enantiomeric excess: 94% ee by chiral HPLC (Chiracel
OJ , isocratic, hexane/2-propanol 90:10, tR [(S)-5e] ) 22.8 min,
tR [(R)-5e] ) 30.3 min). Rf (95:5 hexane/EtOAc) ) 0.25. 1H
NMR (CDCl3, 500 MHz): δ 7.40-7.30 (m, 7H), 6.91 (d, J )
7.9 Hz, 2H), 4.40-4.39 (m, 1H), 4.38-4.37 (m, 1H), 4.18-4.17
(m, 1H), 4.11 (s, 5H), 4.10-4.07 (m, 1H), 3.83 (s, 3H). 13C NMR
(CDCl3, 125 MHz): δ 160.4, 135.5 (d, J ) 21.3 Hz, 2C), 133.0
(d, J ) 19.0 Hz, 2C), 128.3, 128.2 (d, J ) 6.3 Hz, 2C), 114.0 (d,
J ) 8.1 Hz, 2C), 73.4 (d, J ) 18.4 Hz, 1C), 72.4 (d, J ) 10.9
Hz, 1C), 70.9 (d, J ) 4.0 Hz, 2C), 69.3 (s, 5C), 55.3. 31P NMR
(CDCl3, 121 MHz): δ -17.7. HRMS (EI): m/z calcd for C23H21
FeOP 400.0674, obsd 400.0672.
-
(R)-F er r ocen yl(2-m et h oxyp h en yl)p h en ylp h osp h in e
(1f).9a Yield: 83% (0.26 g, 0.65 mmol). Enantiomeric excess:
>98% ee by chiral HPLC analysis (Chiracel OJ , isocratic,
hexane/2-propanol 99:1, tR [(R)-5f] ) 43.8 min, tR [(S)-5f] )
56.9 min). Rf (90:10 hexane/EtOAc) ) 0.31. Mp: 128-130 °C.
1H NMR (CDCl3, 500 MHz): δ 7.50-7.46 (m, 2H), 7.35-7.29
(m, 4H), 6.94-6.91 (m, 1H), 6.89-6.87 (m, 1H), 6.85-6.83 (m,
1H), 4.41-4.40 (m, 1H), 4.35-4.34 (m, 1H), 4.30-4.29 (m, 1H),
4.12 (s, 5H), 3.85-3.84 (m, 1H), 3.73 (s, 3H). 13C NMR (CDCl3,
125 MHz): δ 160.9 (d, J ) 15.5 Hz), 138.0, 133.8 (d, J ) 20.1
Hz, 2C), 130.2, 128.6, 128.0 (d, J ) 7.5 Hz, 2C), 120.9, 110.3
(d, J ) 1.7 Hz), 74.1 (d, J ) 24.7 Hz), 72.3 (d, J ) 4.6 Hz),
71.1 (d, J ) 5.8 Hz), 70.6 (s, 1C), 69.3 (s, 5C), 55.8. 31P NMR
(CDCl3, 121 MHz): δ -28.8 (s). HRMS (EI): m/z calcd for
C
13H24NaO 219.1719, obsd 219.1723.
(E)-1-P h en yl-2-p r op yl-h ex-2-en -1-ol (7).43 Enantiomeric
excess determined by chiral HPLC analysis (Chiracel OD,
isocratic, 99:1 hexane/2-propanol, 0.8 mL/min, tR [(R)-7] ) 15.7
min, tR [(S)-7] ) 17.4 min). Rf (90:10 hexane/EtOAc) ) 0.28.
IR (thin film): 3365, 2958, 2930, 2871, 1493, 1453, 1377, 1035
cm-1. 1H NMR (CDCl3, 500 MHz): δ 7.38-7.31 (m, 4H), 7.29-
7.25 (m, 1H), 5.64 (5, 1H, J ) 7.3 Hz), 5.17 (d, 1H, J ) 3.1
Hz), 2.09-2.05 (m, 2H), 2.01-1.96 (m, 1H), 1.86-1.81 (m, 1H),
1.81 (d, 1H, J ) 3.1 Hz), 1.48-1.40 (m, 2H), 1.34-1.19 (m,
3H), 0.94 (t, 3H, J ) 7.3 Hz), 0.83 (t, 3H, J ) 7.3 Hz). 13C
NMR (CDCl3, 125 MHz): δ 143.0, 141.4, 128.4, 127.54, 127.49,
126.8, 78.4, 30.2, 29.9, 23.2, 23.0, 14.7, 14.2. HRMS (ESI) [M
+ Na]+: m/z calcd for C15H22NaO 241.1564, obsd 241.1564.
(E)-5-P r op yl-n on -5-en -4-ol (8). Enantiomeric excess de-
termined from the chloroacetate derivative by chiral GC
analysis (B-PH, isothermal, 120 °C, tR [(S)-8] ) 21.2 min, tR
[(R)-8] ) 21.9 min). Rf (90:10 hexane/EtOAc) ) 0.25. IR (thin
C
23H21FeOP 400.0674, obsd 400.0672.
(R)-Fer r ocen yl(2-m eth ylph en yl)ph en ylph osph in e (1g).
Yield: >99% (0.42 g, 1.1 mmol), crystallized from diethylamine
upon cooling and standing. The crystals were purified via
column chromatography. Enantiomeric excess: >98% ee by
chiral HPLC analysis (Chiracel OJ , isocratic, hexane/2-pro-
panol 99:1, tR [(R)-5g] ) 14.0 min, tR [(S)-5g] ) 20.3 min). Rf
(90:10 hexane/EtOAc) ) 0.42. Mp: 116-117 °C. 1H NMR
(CDCl3, 500 MHz): δ 7.54-7.51 (m, 2H), 7.40-7.38 (m, 3H),
7.25-7.21 (m, 1H), 7.15-7.11 (m, 2H), 6.99-6.97 (m, 1H),
4.48-4.47 (m, 1H), 4.41-4.38 (m, 2H), 4.14 (s, 5H), 3.80-3.79
(m, 1H), 2.31(s, 3H). 13C NMR (CDCl3, 125 MHz): δ 141.1 (d,
J ) 23.6 Hz), 138.8 (d, J ) 11.5 Hz), 136.8 (d, J ) 7.5 Hz),
134.5 (d, J ) 19.6 Hz, 2C), 132.1, 130.0 (d, J ) 4.0 Hz), 129.1,
128.4, 128.3 (d, J ) 7.5 Hz, 2C), 125.7, 75.8 (d, J ) 4.0 Hz),
74.7 (d, J ) 30.5 Hz), 71.9, 71.4 (d, J ) 6.9 Hz), 70.7, 69.3 (s,
5C), 24.2 (d, J ) 20.1 Hz). 31P NMR (CDCl3, 121 MHz): δ -23.4
(s). HRMS (EI): m/z calcd for C23H21FeP 384.0725, obsd
384.0735.
film): 3357, 2958, 2872, 1465, 1378, 1017 cm-1 1H NMR
.
(CDCl3, 500 MHz): δ 5.39 (t, 1H, J ) 7.3 Hz), 4.03 (td, 1H, J
) 2.5, 6.5 Hz), 2.07-1.94 (m, 4H), 1.54-1.50 (m, 2H), 1.46-
1.53 (m, 5H) 1.33-1.26 (m, 2H), 0.95-0.90 (m, 9H). 13C NMR
(CDCl3, 125 MHz): δ 142.2, 127.0, 76.9, 38.2, 29.9, 29.8, 23.5,
23.2, 19.4, 14.9, 14.3, 14.1. HRMS (ESI) [M + Na]+: m/z calcd
for C12H24NaO 207.1719, obsd 207.1723.
(E)-2-Meth yl-4-p r op yl-oct-4-en -3-ol (9). Enantiomeric ex-
cess determined from the chloroacetate derivative by chiral
GC analysis (B-PH, 90 °C for 30 min then 140 °C for 15 min,
tR [(S)-9] ) 38.4 min, tR [(R)-9] ) 38.9 min). Rf (90:10 hexane/
EtOAc) ) 0.34. IR (thin film): 3409, 2958, 2931, 2872, 1466,
1379, 1005 cm-1. 1H NMR (CDCl3, 500 MHz): δ 5.35 (t, 1H, J
) 7.3 Hz), 3.65 (d, 1H, J ) 7.3 Hz), 2.05-1.92 (m, 4H), 1.81-
1.75 (m, 1H), 1.47-1.35 (m, 5H) 0.98-0.89 (m, 9H), 0.83 (t,
3H, J ) 7.0 Hz). 13C NMR (CDCl3, 125 MHz): δ 141.4, 127.9,
83.0, 31.8, 30.3, 29.8, 23.5, 20.1, 18.3, 14.9, 14.1. HRMS (ESI)
[M + Na]+: m/z calcd for C12H24NaO 207.1719, obsd 207.1716.
(E)-1-Cycloh exyl-2-m eth yl-h ex-1-en -3-ol (10a ) a n d (E)-
3-Cycloh exyl-h ep t-2-en -4-ol (10b). Enantiomeric excess de-
termined by chiral GC analysis (B-PH, isothermal, 140 °C, tR
(R)-F er r ocen yl(2-b ip h en ylyl)p h en ylp h osp h in e (1h ).
Yield: 94% (0.30 g, 0.7 mmol). Enantiomeric excess: 96% ee
by chiral HPLC analysis (Chiracel AD, isocratic, hexane/2-
propanol 99.4:0.6, tR [(R)-5h ] ) 13.2 min, tR [(S)-5h ] ) 14.3
min). Rf (90:10 hexane/EtOAc) ) 0.40. Mp: 63-65 °C. 1H NMR
(CDCl3, 500 MHz): δ 7.38-7.23 (m, 11H), 7.21-7.18 (m, 1H),
7.13-7.12 (m, 2H), 4.43-4.43 (m, 1H), 4.37-4.36 (m, 1H),
4.34-4.33 (m, 1H), 4.0 (s, 5H), 3.86-3.85 (m, 1H). 13C NMR
(CDCl3, 125 MHz): δ 146.9 (d, J ) 24.4 Hz), 141.9 (d, J ) 5.2
Hz), 139.1 (d, J ) 15.0 Hz), 138.3 (d, J ) 8.1 Hz), 134.5 (d, J
) 20.1 Hz, 2C), 132.9, 130.0 (d, J ) 3.5. Hz), 129.8 (d, J ) 3.5
Hz, 2C), 128.7, 128.2, 128.0 (d, J ) 8.1 Hz, 2C), 127.7 (s, 2C),
127.1 (s, 2C), 76.6 (d, J ) 7.5 Hz), 74.9 (d, J ) 31.9 Hz), 72.0,
71.2 (d, J ) 6.9 Hz), 70.7, 69.2 (s, 5C). 31P NMR (CDCl3, 121
MHz): δ -22.0 (s). HRMS (EI): m/z calcd for C28H23FeP
446.0887, obsd 446.0871.
(43) Srebnik, M. Tetrahedron Lett. 1991, 32, 2449-2452.
J . Org. Chem, Vol. 68, No. 1, 2003 165

Colby and J amison
[(R)-10b] ) 7.86 min, tR [(S)-10b] ) 8.03 min, tR [(R)-10a ] )
11.40 min, tR [(S)-10a ] ) 11.66 min,). IR (thin film): 3348,
2926, 2852, 1448 cm-1. Rf (90:10 hexane/EtOAc) ) 0.33. 1H
NMR (CDCl3, 500 MHz): δ 5.51 (q, 1H, 10b, J ) 7.0 Hz), 5.20
(d, 1H, 10a , J ) 8.8 Hz), 4.05 (t, 1H, 10b, J ) 5.5 Hz), 3.96 (t,
1H, 10a , J ) 6.7 Hz), 2.37-2.33 (m, 1H, 10b), 2.21-2.15 (m,
1H, 10a ), 1.78-0.87 (m, 21H, 10a , 10b). 13C NMR (CDCl3, 125
MHz): δ 148.0, 135.4, 133.1, 119.6, 78.0, 73.6, 39.4, 38.9, 37.2,
36.7, 33.3, 33.2, 31.6, 31.4, 27.2, 26.4, 26.3, 26.18, 26.17, 19.7,
19.2, 14.28, 14.25, 13.5, 12.8, 11.3. HRMS (ESI) [M + Na]+:
m/z calcd for C13H24NaO 219.1719, obsd 219.1724.
12 and 13, respectively. We thank the National Science
Foundation (CAREER, CHE-0134704), Merck Research
Laboratories, Pfizer, Boehringer-Ingelheim, J ohnson &
J ohnson, 3M, the donors of the Petroleum Research
Fund, the American Society for Engineering Education
(NDSEG fellowship awarded to E.A.C.), and MIT for
generous financial support. Funding for the MIT De-
partment of Chemistry Instrumentation Facility has
been provided in part by NSF Grants CHE-9809061 and
NSF DBI-9729592 and by NIH Grant 1S10RR13886-
01.
Ack n ow led gm en t. We are grateful to members of
the Prof. G. C. Fu research lab for their assistance with
chiral HPLC analysis of compounds 5d , 5h , 6a , and
8-10, and to Dr. Li Li of the MIT Department of
Chemistry Instrumentation Facility for obtaining mass
spectrometric data for all compounds. We thank J ohann
Chan and Sejal Patel of our laboratory for samples of
Su p p or tin g In for m a tion Ava ila ble: 1H, 13C, and 31P
1
NMR spectra for 1a -h , 3a -h , 4a -h , and 5a -h ; H and 13C
NMR spectra for 6a ,b, 7-9, and 10a ,b. This material is
available free of charge via the Internet at http://pubs.acs.org.
J O0264123
166 J . Org. Chem., Vol. 68, No. 1, 2003