Sequencing cross-metathesis and non-metathesis reactions to rapidly access building blocks for synthesis

Article abstract of DOI:10.1016/j.tet.2011.01.080

The olefin cross-metathesis reaction has been sequenced with four common organic transformations in a one- or two-pot manner to rapidly access useful building blocks. Those reactions are: (1) phosphorus-based olefination (e.g., Wittig and Horner-Wadsworth-Emmons); (2) hydride reduction; (3) Evans propionate aldol reaction; (4) Brown allyl- and Roush crotyl-boration. The products of these reactions include stereodefined 2,4-dienoates, trans allylic alcohols, syn-propionate aldols, and chiral non-racemic homoallylic alcohols, respectively. Many of these intermediates have been carried further to natural products, demonstrating the utility of the methodology.

Full text of DOI:10.1016/j.tet.2011.01.080

Tetrahedron 67 (2011) 2197e2205
Contents lists available at ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Sequencing cross-metathesis and non-metathesis reactions to rapidly access
building blocks for synthesis
*
Gopal Sirasani, Tapas Paul, Rodrigo B. Andrade
Temple University, Department of Chemistry, Philadelphia, PA 19122, United States
a r t i c l e i n f o
a b s t r a c t
Article history:
The olefin cross-metathesis reaction has been sequenced with four common organic transformations in
a one- or two-pot manner to rapidly access useful building blocks. Those reactions are: (1) phosphorus-
based olefination (e.g., Wittig and HornereWadswortheEmmons); (2) hydride reduction; (3) Evans
propionate aldol reaction; (4) Brown allyl- and Roush crotyl-boration. The products of these reactions
include stereodefined 2,4-dienoates, trans allylic alcohols, syn-propionate aldols, and chiral non-racemic
homoallylic alcohols, respectively. Many of these intermediates have been carried further to natural
products, demonstrating the utility of the methodology.
Received 10 December 2010
Received in revised form 25 January 2011
Accepted 26 January 2011
Available online 2 February 2011
Keywords:
One-pot
Tandem
Ó 2011 Elsevier Ltd. All rights reserved.
Cross-metathesis
Olefination
2,4-Dienoates
trans Allylic alcohols
Evans aldol
Brown allylboration
Roush crotylboration
1. Introduction
generation catalyst (Grubbs-II)11 (1) or Hoveyda-Grubbs second-gen-
eration catalyst (HG-II) (2),9,12 terminal and electron-deficient olefins
Current organic synthesis and synthetic methodology is largely
driven by the goals of maximizing the efficiency (i.e., atom,1 step,2 re-
dox economy3) and selectivity (e.g., chemo-, regio-, stereo-)4 by which
target molecules are prepared. Syntheses that employ tandem (se-
quential, ideally one-pot) operations5 or domino (cascade) reactions6
are aligned with this goal; herein, we report our studies on the former.
Sequential (tandem) one-pot reactions by design streamline linear
synthetic processes.7 In addition, yields can often be increased due to
minimization of intermediary purification steps and hence waste
streams, which are time-consuming, expensive, and not environ-
mentally friendly. Olefin cross-metathesis (CM)8 has emerged as
a powerful method for the stereoselective preparation of carbone
carbon double bonds in high yield, particularly when coupling ter-
minal and electron-deficient olefins.9 Terminal olefins are useful
chemical handles (e.g., masked aldehydes) that tolerate a broad range
of synthetic transformations, making them useful in complex mole-
cule total synthesis. Moreover, there has been an appreciation of the
facility by which CM reactions can be sequenced with non-CM re-
actions.10 In the presence of commercially available Grubbs second-
(e.g., crotonaldehyde) can be coupled in high yield and with high E/Z
selectivity (>20:1). The reaction is typically clean, producing an (E)-2-
enal that can be subsequently reacted with various reagents in a one-
pot fashion. Herein, we summarize and report the treatment of this
intermediary enal with (1) Wittig and HornereWadswortheEmmons
reagents; (2) DIBAL-H; (3) N-propionyl oxazolidinones developed by
Evans;13 and (4) asymmetric Brown allylboration14 and Roush cro-
tylboration reagents (Scheme 1).15
2. Results and discussion
2.1. Sequential CM/phosphorus-based olefination
The synthesis of stereodefined 2,4-dienoates generally involves
the iterative olefination of aldehydes using stabilized Wittig16 or
HornereWadswortheEmmons (HWE)17 reactions, which often
require inefficient redox manipulations to access key 2-enal in-
termediates between couplings. While vinylogous phosphonates18
and the chemoselective CM reaction between terminal olefins and
2,4-dienoates19,20 address synthetic inefficiency to a certain extent,
these reagents must be prepared in a stepwise manner with in-
termediary purification. Herein we offer a convenient and efficient
* Corresponding author. Tel.: þ1 215 204 7155; fax: þ1 215 204 9851; e-mail
address: randrade@temple.edu (R.B. Andrade).
0040-4020/$ e see front matter Ó 2011 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2011.01.080

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G. Sirasani et al. / Tetrahedron 67 (2011) 2197e2205
Wittig
or
CO2R4
or
HWE
R
R
MesN NMes
R2 CO2R4
R2 R5
Cl
Ru
Ph
Cl
PCy3
DIBAL-H
R
OH
OH
Grubbs-II (1)
or
R3
R3
R2
+
O
O
R
R1
O
R
O
Evans Aldol
R2
R2
MesN NMes
R
R
N
O
Cl
Ru
Cl
Me
not isolated
Brown allyl-
or Roush
Bn
O
OH
i-Pr
crotylboration
Hoveyda-Grubbs-II (2)
R5
R = alkyl, aryl; R1, R2 = H or Me; R3 = H or OMe; R4 = Me or Et; R5 = H or Me
Scheme 1. Overview of sequential CM/non-CM method to access building blocks.
alternative that employs only commercially available reagents for
the rapid assembly of either (2E,4E)- or (2Z,4E)-dienoates by
modifying the second olefination step.
screening conditions for the second step, we discovered that equi-
molar phosphorane(3.0 equiv)didnotresult inhigherproductyields
and that 1.2 equiv of either 3 or 4 would suffice. Our hypothesis that
excess crotonaldehyde had decomposed over the course of the re-
action was supported by the fact that very little methyl sorbate (the
byproduct of the Wittig reaction and crotonaldehyde) was isolated
fromthereactionmixturewhen3equivof3wereemployed.Yieldsas
high as 77% (entry 1) were realized with this procedure, corre-
sponding to an average of 88% per step. Upon adding phosphorane 3,
the solution was warmed to rt and stirred overnight (12 h). Entry 6
required reflux due to the hindered nature of phosphorane 4.
The one-pot CM/Wittig olefination sequence is summarized in
Table 1. A variety of terminal olefins were prepared and subjected to
5 mol % Grubbs-II (1) and crotonaldehyde in refluxing dichloro-
methane to effect the first cross-metathesis step. It was determined
that refluxing the olefin with an excess (3.0 equiv) of crotonalde-
hyde for 3 h was the optimal protocol.
The reaction mixture was then cooled to 0 ꢀC, treated with a slight
excess of phosphorane 3 and subsequently warmed to rt. While
Table 1
One-pot CM/Wittig olefination for the stereoselective synthesis of (2E,4E)-dienoates
R1
Ph3P
CO2R2
3: R1=H; R2=Me
4: R1=Me; R2=Et
Grubbs-II (1)
(5 mol%)
CO2R2
CHO
+
CHO
not isolated
R
R
Me
R
R1
CH2Cl2
reflux, 3 h
>20/1 E/Z
CH2Cl2
0 °C→rt→reflux
(3 equiv.)
Entry
1
Olefin
Phosphorane
Product
Yielda,b (ratio: 2E/2Z)c
TBSO
TBSO
CO2Me
3
77% (9:1)
10
5
CO2Me
MeO2C
BzO
MeO2C
BzO
2
3
3
3
57% (9:1)
60% (8:1)
6
11
CO2Me
7
12
CO2Me
CO2Me
4
5
3
73% (9:1)
8
13
3
4
48% (11:1)
50% (5:1)
14
9
CO2Et
Me
MeO2C
MeO2C
6
6
15
a
Yields refer to the average of two runs.
Isolated yield of separable E/Z mixture.
Ratio determined by 1H NMR.
b
c

G. Sirasani et al. / Tetrahedron 67 (2011) 2197e2205
2199
All reactions delivered good yields of dienoates 10e15 with
2.2. Sequential CM/hydride reduction
entry 6 affording a trisubstituted (2E,4E)-dienoate. The E/Z geo-
metric isomers were separable by chromatography. While it is
known that stabilized phosphoranes are stereoselective for the
E isomer in the Wittig reaction, we turned our attention to the
HornereWadswortheEmmons (HWE) reaction in order to (1) in-
crease the stereoselectivity of the olefination step and (2) access the
Z-enoate by recruiting the StilleGennari21 phosphonate 18 (vide
infra). Toward this end, we repeated the CM sequence with the
olefin substrates albeit in two pots as HWE reactions are performed
in ethereal solvents (e.g., THF or diglyme). The results are sum-
marized in Table 2.
Operationally, the reaction mixtures were concentrated fol-
lowing the CM step and added to phosphonate anions corre-
sponding to 16e18 at ꢁ78 ꢀC. We were again pleased that yields
ranged from 55% (entry 3) to 83% (entry 1), showing the synthetic
viability of this tandem sequence. The StilleGennari olefination
with phosphonate 18 delivered (2Z,2E)-dienoate 21 in 63% yield
with a good Z/E ratio (6.5:1).
Primary (E)-allylic alcohols are excellent substrates for a variety
of transformations, such as the Sharpless asymmetric epoxidation
reaction,22 which has been heavily utilized in the iterative synthesis
of polyketide natural products.23,24 These substrates are typically
prepared in the three-step sequence due to the need for redox
manipulation: (1) oxidation of a primary alcohol or terminal olefin
to the aldehyde; (2) olefination of the resulting aldehyde with
a phosphorus-based reagent (e.g., phosphorane, phosphonate); and
(3) 1,2-reduction of the enoate to the primary (E)-allylic alcohol
(Scheme 2a). A shorter alternative route features a CM between
a terminal olefin and allyl alcohol (Scheme 2b). While this short
route is attractive, the stereoselectivity of the transformation is
highly dependent on the nature of ‘R’ such that an increase in steric
bulk favors the (E) geometric isomer.25,26
By sequencing (1) the highly (E)-selective CM reaction of
an electron-rich terminal olefin and an electron-poor olefin
In order to expand the scope of this methodology, we wanted to
study what other a,b-unsaturated aldehydes could be used in the
sequence. While (E)-2-methyl-2-butenal failed to react after 12 h
under reflux, recourse to methacrolein (3 equiv) resulted in a fa-
vorable reaction (entry 2). Olefination with trimethyl phospho-
noacetate (16) yielded 81% of dienoate 20 with excellent 2E,2Z
selectivity (20:1). Finally, tandem CM/HWE with phosphonopro-
pionate 17 afforded dienedioate 15 in 69% with good 2E,2Z selec-
tivity (5:1), which was also prepared via one-pot CM/Wittig (see
Table 1, entry 6) albeit in lower yield (50%).
Scheme 2. Routes to primary (E)-allylic alcohols: (a) traditional; (b) CM.
Table 2
Tandem CM/HWE olefination for the stereoselective synthesis of (2E,4E)- or (2Z,4E)-dienoates
R3
(R5O)2(O)P
CO2R4
16: R3=H; R4=R5=Me
17: R3=Me; R4=R5=Et
18: R3=H;R4=Me;
R5=CH2CF3
CHO
Me
Grubbs II 1
CO2R4
(5 mol%)
CHO
or
+
R
R
R
CH2Cl2
reflux, 3 h
>20/1 E/Z
R2 R3
CHO
THF or diglyme
R2
-78 °C→rt
R2=H or Me
not purified
Me
Entry
1
Olefin
Aldehyde (3 equiv)
Phosphonate
Product
Yielda,b (ratio: 2E/2Z)c
TBSO
TBSO
TBSO
TBSO
CO2Et
Me
CHO
Me
17
83% (20:1)
19
5
CO2Me
CHO
Me
2
3
16
16
81% (20:1)
55% (18:1)
Me
5
20
CO2Me
CHO
Me
14
9
CHO
Me
4
18
17
63% (1:6.5)
69% (5:1)
CO2Me
21
9
CO2Et
Me
MeO2C
CHO
Me
MeO2C
5
6
15
a
Yields refer to the average of two runs.
Isolated yield of separable E/Z mixture.
Ratio determined by 1H NMR.
b
c

2200
G. Sirasani et al. / Tetrahedron 67 (2011) 2197e2205
(i.e., acrolein, acrylate, etc.)26 with (2) a hydride reduction step, the
stereochemical fidelity of the product is preserved. Table 3 shows
a variety of terminal olefins that were subjected to this one-pot
for 2 h. Of note are chemoselective CM entries 3 and 6, which afford
alcohols 38 and 41 due to the bulky TBS protecting group that
sterically shields the allylic site.30 Synthetically useful yields
(54e74%) were obtained for both allylated (entries 1e3) and cro-
tylated (entries 4e6) substrates.
method. Styrene (9) and a series of TBS-protected
a,u-alkenols
were treated with 3 equiv of either crotonaldehyde or methacrolein
and 5 mol % Grubbs-II (1) in refluxing CH2Cl2 for 3 h to afford in-
termediary a,b
-enals in high yield and high dr (>20:1 E/Z by 1H
2.3. Sequential CM/Evans aldol reactions
NMR).27 As these reactions proceed cleanly and in high yield (a
priori requirements for efficient one-pot procedures), the reaction
mixtures were subsequently cooled to ꢁ78 ꢀC and treated with
excess DIBAL-H (commercially available solution in hexanes),
affording exclusively primary (E)-allylic alcohols 24e29 in syn-
thetically useful yields (59e74%). The temperature regime was
necessary to avoid undesired 1,4-reduction. The substitution of the
double bond is controlled by choice of either crotonaldehyde or
methacrolein.
The Evans aldol reaction is arguably the most powerful and
versatile means of preparing propionate aldol subunits in a stoi-
chiometric asymmetric manner.13 The levels of diaster-
eoselectivity enjoyed by the robust N-acyl oxazolidinones (in both
single and double asymmetric synthesis) and facile nature of their
manipulation have made the Evans aldol methodology popular in
the synthesis of complex natural products, particularly poly-
ketides.13 As the products of CM reactions of terminal olefins and
Table 3
One-pot sequential CM/hydride reduction method for the stereoselective synthesis of primary (E)-allylic alcohols with the Grubbs-II catalyst (1)
Entry
1
Olefin
Coupling partner (3 equiv)
Product
Yielda dr > 20:1 (E/Z)b
OH
CHO
Me
70%
24
9
TBSO
TBSO
TBSO
CHO
Me
OH
2
3
4
74%
72%
56%
5
25
OH
TBSO
CHO
Me
22
22
26
CHO
Me
TBSO
TBSO
OH
TBSO
TBSO
Me
27
28
CHO
Me
OH
5
69%
59%
5
Me
CHO
Me
TBSO
OH
TBSO
6
Me
23
29
a
Yields refer to the average of two runs.
Ratio determined by 1H NMR.
b
With these results in hand, we turned our attention to more
crotonaldehyde (or methacrolein) led to (E)-2-enals, which are
substrates for the Evans aldol reaction, we investigated sequenc-
ing our method with the Evans propionate aldol reaction to rap-
idly access building blocks. To substantiate the utility in synthesis,
we deliberately chose substrates that had been previously pre-
pared in a stepwise manner and subsequently employed in total
synthesis.
synthetically useful terminal olefins 30e35 (Table 4). The allylation
and crotylation reaction of aldehydes represents formidable alter-
natives to the acetate and propionate aldol reactions, respectively.
These methodologies have been leveraged in the stereoselective
total synthesis of natural products, particularly those of polyketide
origin.28 As the products of these reactions are terminal olefins,
they represent excellent substrates for our methodology. Toward
this goal, a variety of protected homoallylic alcohols 30e32 were
prepared by the addition of allylmagnesium bromide to the cor-
responding aldehyde, whereas 33e35 were prepared in an asym-
metric manner by the addition of Roush’s tartrate-functionalized
(E)-crotylboronate to the corresponding aldehyde.15 For these
substrates, we found that the combination of 10 mol % Hoveyda-
Grubbs-II (2) catalyst and 3 equiv of methyl acrylate as coupling
partner gave the best results.29 Following the addition of DIBAL-H
at ꢁ78 ꢀC, the reaction mixture was warmed to ꢁ45 ꢀC and stirred
Table 5 shows four examples. Styrene (9) and a series of pro-
tected allyl ethers were treated with 3 equiv of crotonaldehyde and
5 mol % Hoveyda-Grubbs II (2) in refluxing CH2Cl2 for 12 h to afford
intermediary a,b
-enals in high yield and high dr (>20:1 E/Z by 1H
NMR).31 In a separate reaction vessel, Evans propionimide 42 (or
ent-42 for entry 3) was enolized under standard reaction conditions
(Bu2BOTf, Et3N or i-Pr2NEt, CH2Cl2 at ꢁ78 ꢀC). To this was added
a solution of enal derived from the CM reaction, and the corre-
sponding aldol products 46e49 were isolated in good yields
(48e64%) with excellent diastereoselectivities (dr>20:1).32

G. Sirasani et al. / Tetrahedron 67 (2011) 2197e2205
2201
Table 4
Table 5
One-pot sequential CM/hydride reduction method for the stereoselective synthesis
of primary (E)-allylic alcohols with the Hoveyda-Grubbs-II catalyst (2)
Sequential CM/Evans aldol reaction for the asymmetric synthesis of unsaturated
propionate aldols with 5 mol % Grubbs-II catalyst (1)
Entry
1
Olefin
Product
Yielda dr > 20:1
(E/Z)b
Entry
1
Olefin
Evans
reagent
Product
Yield
OBn
(dr > 20:1)a,b
OBn
Me
Me
O
59%
HO
O
OH
30
36
N
O
42
42
60%
48%
Me
9
OTBS
Bn
OTBS
46
2
3
56%
54%
Ph
OH
Ph
O
HO
O
31
37
TBSO
TBSO
N
O
2
3
OTBS
OTBS
43
Me
47
Bn
Ph
OH
Ph
32
38
O
HO
O
OTBS
OTBS
BnO
BnO
N
O
ent-42
52%
64%
Me
Me
4
5
64%
57%
74%
44
OH
Me
48
Bn
39
Me
Me
33
O
HO
O
OTBS
OTBS
PMBO
PMBO
45
N
O
4
42
Ph
40
OH
Ph
Me
49
34
Me
Me
Bn
a
OTBS
OTBS
Yields refer to the average of two runs.
b
Aldol diastereoselectivity ratio (dr) determined by 1H NMR.
6
Ph
OH
Ph
Me
35
Me
41
allylic alcohols, the Evans aldol reaction to prepare diastereomeri-
cally pure syn-propionate aldols, and finally the Brown allyl- and
Roush crotylboration reactions to furnish enantioenriched homo-
allylic alcohols. Most of the products of these reactions have been
employed in total synthesis, thus validating the utility of this
method in telescoping linear total synthesis and enabling greener,
more efficient routes to complex targets (i.e., natural products).
a
Yields refer to the average of two runs.
Ratio determined by 1H NMR.
b
2.4. Sequential CM/Roush allyl- and crotyl-boration reactions
The allyl- and crotyl-metalation of aldehydes represents pow-
erful surrogates for the acetate and propionate aldol reactions, re-
spectively.33 Thus, they have found widespread use in the total
synthesis of polyketides.34 Brown and Roush have both developed
some of most utilized stoichiometric allyl- and crotyl-boration
methodologies.15 As we had shown the utility of sequencing CM
with the Evans aldol reaction (vide supra), we opted to employ
Brown’s Ipc-controlled allylboration and Roush’s tartrate-derived
crotylborates. Table 6 shows six examples of those products, which
are known intermediates previously employed in natural product
total syntheses.35 Styrene (9) and a series of olefins (53e55) were
subjected to the standard CM sequence. Following concentration
and solvent exchange, the solution of enal was transferred to an-
other reaction vessel containing Brown’s allylborane 50 or Roush’s
(E)-crotylboronate 51 at ꢁ78 ꢀC to afford allylated enantioenriched
homoallylic alcohols 56e61 in high yields (71e82%) and good se-
lectivities (67e88% ee).
4. Experimental section
4.1. General
All reactions containing moisture or air sensitive reagents were
performed in oven-dried glassware under nitrogen or Argon.
Diethyl ether, tetrahydrofuran, toluene, and dichloromethane were
passed through two columns of neutral alumina. Diglyme, i-Pr2NEt,
and Et3N were distilled from CaH2 prior to use. Molecular sieves
ꢀ
(4 A) were activated by flame drying under vacuum prior to use.
Crotonaldehyde and methacrolein were freshly distilled prior to
use. Evans propionimides (42, ent-42) and Brown allylborane 50
and Roush crotylboronates 51 were prepared according to literature
procedures, respectively.13,15 All other reagents were purchased
from commercial sources and used without further purification. All
solvents for work-up procedures were used as received. Flash col-
umn chromatography was performed according to the procedure of
3. Conclusion
Still36 using ICN Silitech 32-63 D 60 A silica gel with the indicated
ꢀ
In conclusion, we have demonstrated the utility of sequencing
olefin cross-metathesis with various non-metathesis reactions. The
scope of this method now includes the Wittig and Hor-
nereWadswortheEmmons olefination reactions to access stereo-
defined dienoates, hydride-mediated reduction to furnish trans
solvents. For all reactions involving cross-metathesis, CH2Cl2 was
deaerated by bubbling Argon through the solution (1 min/mL).
Enantiomeric excess (% ee) for Brown allylation and Roush cro-
tylboration reactions was determined by the Mosher method.37
Thin layer chromatography was performed on Analtech 60 F254

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G. Sirasani et al. / Tetrahedron 67 (2011) 2197e2205
Table 6
Paolo, C.; Cristina, G.; Granco, M.; Mauro, P. Tetrahedron 1995, 51,
10,601. Compound 13: Wang, J.; Hsung, R.P.; Ghosh, S.K. Org. Lett.
2004, 6, 1939. Compound 14: Nicolaou, K.C.; Prasad, C.V.C.; Hwang,
C.-K.; Duggan, M.E.; Veale, C.A. J. Am. Chem. Soc. 1989, 111, 5321.
Compound 15: Hayashi, Y.; Kanayama, J.; Yamaguchi, J.; Shoji, M. J.
Org. Chem. 2002, 67, 9443. Compound 46: Evans, D. A.; Bender, S. L.;
Morris, J. J. Am. Chem. Soc. 1998, 110, 2506. Compound 47: Vander-
wal, C. D.; Vosberg, D. A.; Sorensen, E. J. Org. Lett. 2001, 3, 4307.
Compound 48: Anderson, J. C.; McDermott, B. P.; Griffin, E. J. Tet-
rahedron 2000, 56, 8747. Compound 49: Garcia-Fortanet, J.; Murga,
J.; Carda, M.; Alberto Marco, J.; Matesanz, R.; Fernando Diaz, J.;
Barasoain, I. Chem. Eur. J. 2007, 13, 5060. Compounds 56, 58, 59:
Fatima, A.D.; Kohn, L.K.; Carvalho, J.E.; Pilli, R.A.; Bioorg. Med. Chem.
2006, 14, 622. Compound 57: Roush, W.R.; Hoong, L.K.; Palmer,
M.A.J.; Park, J.C.; J. Org. Chem. 1990, 55, 4109.
Sequential CM/Brown allyl- or Roush (E)-crotylation reactions for the asymmetric
synthesis of homoallylic alcohols with 5 mol % Grubbs-II catalyst (1)
Entry
1
Olefin
Reagent
Product
Yielda,b
HO
50
74% (83% ee)
9
56
HO
H15C7
Compounds 60, 61: Roush, W.R.; Ando, K.; Powers, D.B.; Palko-
witz, A.D.; Halterman, R.L. J. Am. Chem. Soc., 1990, 112, 6339.
2
3
50
50
75% (88% ee)
72% (82% ee)
H15C7
53
57
HO
4.2. General procedure for sequential one-pot CM/Wittig
reactions (Table 1)
58
54
Crotonaldehyde (101 mg, 1.45 mmol) dissolved in deaerated
CH2Cl2 (2.2 mL) was added to a solution of olefin (0.48 mmol) in
deaerated CH2Cl2 (1.0 mL). Grubbs’ second-generation catalyst 1
(20 mg, 5 mol %) was added, and the reaction mixture was heated
to 40 ꢀC under an Ar atmosphere for 3 h. The reaction mixture was
cooled to 0 ꢀC, and phosphorane 2 (194 mg, 0.58 mmol) was added.
The reaction was stirred at rt for 15 h (for entries 2 and 6, reaction
was refluxed for 1 h), concentrated under reduced pressure, and
purified by flash column chromatography eluting with 2e10% ethyl
acetate/hexanes.
HO
4
5
50
51
51
71% (83% ee)
F
55
59
F
HO
80%
(dr > 20:1) (67% ee)
Me
Me
9
60
HO
H15C7
53
82%
4.3. General procedure for sequential one-pot CM/HWE
reactions (Table 2dentries 1, 2, and 5)
6
H15C7
(dr > 20:1) (86% ee)
61
Sodium hydride (28 mg, 0.69 mmol) was added to a solution of
phosphonate (0.69 mmol) in THF or diglyme (5.0 mL) at 0 ꢀC. The
reaction mixture was stirred for 30 min. The crude enal
(0.48 mmol) derived from the cross-metathesis step (see above
Experimental) was dissolved in THF or diglyme (3.0 mL) and added
to the phosphonate solution. The reaction mixture was warmed to
rt and stirred for 15 h. Diethyl ether (10 mL) was added, and the
reaction was quenched with saturated aq NH4Cl (5 mL). The
aqueous phase was extracted with diethyl ether (2ꢂ20 mL). The
combined organic layers were washed with water (2ꢂ10 mL), brine
(2ꢂ10 mL), dried over Na2SO4, and concentrated under reduced
pressure. The residue was purified by flash column chromatogra-
phy eluting with 2e10% EtOAc/hexanes.
a
Enantiomeric excess (% ee) determined by Mosher ester analysis.
b
Crotylation anti/syn ratio (dr) determined by 1H NMR.
silica gel plates. Detection was performed using UV light, KMnO4
stain, PMA stain, and subsequent heating. 1H and 13C NMR spectra
were recorded at the indicated field strength in CDCl3 at rt.
Chemical shifts are indicated in parts per million (ppm) downfield
from tetramethylsilane (TMS,
Splitting patterns are abbreviated as follows: s (singlet), d (dou-
blet), t (triplet), q (quartet), and m (multiplet).
d¼0.00) and referenced to the CDCl3.
Spectral data (1H and 13C NMR) for the following known re-
action products were consistent with literature values: Compound
9: Spino, C.; Rezaei, H.; Dupont-Gaudet, K.; Belanger, F. J. Am. Chem.
Soc. 2004, 126, 9926. Compound 10: Xuan, J.X.; Fry, A.J. Tetrahedron
Lett. 2001, 42, 3275. Compound 11: Montserrat, C.; de March, P.;
Figueredo, M.; Font, J.; Soria, A. Tetrahedron 1997, 53, 16,803.
Compound 12: Horsham, M.A.; Class, T.J.; Johnston, J.J.; Casida, J.E.J.
Agric. Food Chem. 1989, 37, 777. Compound 25: Takano, S.; Seki-
guchi, Y.; Shimazaki, Y.; Ogasawara, K. Heterocycles 1992, 33, 713.
Compound 16: Yadav, J.S.; Rao, E. Sreenivasa. Synth. Commun. 1988,
18, 2315. Compound 17: Hiebel, M.-A.; Pelotier, B.; Piva, O. Tetra-
hedron 2007, 63, 7874. Compound 19: Masamune, S.; Kaiho, T.;
Garvey, D.S. J. Am. Chem. Soc. 1982, 104, 5521. Compound 13: Kim,
D.D.; Lee, S.J.; Beak, P. J. Org. Chem., 2005, 70, 5376. Compound 13:
Murelli, R.P.; Snapper, M.L. Org. Lett. 2007, 9, 1749. Compound 20:
Touchard, F.P. Tetrahedron Lett. 2004, 45, 5519. Compound 10:
Pospisil, J.; Marko, I.E. Org. Lett. 2006, 8, 5983. Compound 11: Nic-
olaou, K.C.; Prasad, C.V.C.; Somers, P.K.; Hwang, C.-K. J. Am. Chem.
Soc. 1989, 111, 5330. Compound 12: Francesca, A.; Federico, C.;
4.4. General procedure for sequential one-pot CM/HWE
reactions (Table 2dentries 3 and 4)
KHMDS (1.06 mL, 0.5 M in toluene, 0.53 mmol) was added to
a solution of phosphonate (0.53 mmol) in THF (5.0 mL) at ꢁ78 ꢀC.
The reaction mixture was stirred for 30 min. The crude enal
(0.48 mmol) derived from the cross-metathesis step (see above
Experimental) was dissolved in THF (3.0 mL) and added to the
phosphonate solution. The reaction mixture was stirred at ꢁ78 ꢀC
for 4 h. Et2O (10 mL) was added, and the reaction was quenched
with saturated aq NH4Cl (5 mL). The aqueous phase was extracted
with diethyl ether (2ꢂ20 mL). The combined organic layers were
washed with water (2ꢂ10 mL), brine (2ꢂ10 mL), dried over Na2SO4,
and concentrated under reduced pressure. The residue was purified
by flash column chromatography eluting with 2e10% ethyl acetate/
hexanes.

G. Sirasani et al. / Tetrahedron 67 (2011) 2197e2205
2203
4.5. General procedure for sequential one-pot CM/hydride
reduction reactions (Tables 3 and 4)
liquid. NMR spectra (1H and 13C) were identical with reported
literature values.
To a solution of olefin (0.48 mmol) and
a
,
b
-unsaturated car-
4.6.3. Aldol 48. Hoveyda-Grubbs II (2) (11 mg, 0.017 mmol) was
added to a mixture of benzyl ether 44 (50 mg, 0.337 mmol) and
crotonaldehyde (47 mg, 0.674 mmol) in deaerated CH2Cl2 (2.2 mL).
The reaction mixture was heated to 40 ꢀC under an Ar atmosphere
for 12 h and cooled to rt. The solvent was concentrated under re-
duced pressure and the residue was dried under vacuum for
10 min. To a solution of ent-42 (79 mg, 0.337 mmol) in CH2Cl2
bonyl partner (1.45 mmol) in deaerated CH2Cl2 (3.0 mL) was
added catalyst 1 or 2 (5e10 mol %). The reaction mixture was
heated to 40 ꢀC under an Ar atmosphere and stirred for 3 h. The
reaction mixture was cooled to ꢁ78 ꢀC, and DIBAL-H (1 M in
hexanes, 1.8 mL, 1.80 mmol) was added dropwise. The reaction
mixture was stirred at ꢁ78 ꢀC for 2 h and quenched by the slow
addition of MeOH (1.8 mL) followed by a saturated solution of
Rochelle’s salt (1.8 mL). The reaction mixture was warmed to rt
and filtered through a cotton plug. The residue was washed
thoroughly with CH2Cl2 (3ꢂ10 mL). The combined organic layers
were washed with brine (2ꢂ10 mL), dried over Na2SO4, and
concentrated under reduced pressure. The residue was purified
by flash column chromatography eluting with 20% EtOAc/
hexanes.
(2 mL) was added
a 1.0 M solution of Bu2BOTf (0.41 mL,
0.405 mmol) at ꢁ10 ꢀC over 2 min followed by Et3N (44 mg,
0.438 mmol) making sure that the internal temperature is below
0 ꢀC and stirred for 30 min at 0 ꢀC. The reaction mixture was cooled
to ꢁ78 ꢀC and the metathesis product was added slowly using
CH2Cl2 (2 mL) and stirred for 45 min, warmed to 0 ꢀC, and
stirred for additional 3 h. The yellow orange solution was recooled
to ꢁ10 ꢀC and quenched by adding pH 7 buffer (2 mL), MeOH
(2 mL), and a mixture of MeOH, 30% H2O2 (1þ0.5 mL). The reaction
mixture was extracted with CH2Cl2 (3ꢂ10 mL), washed with
NaHCO3 (10 mL), brine (10 mL), and dried over Na2SO4, purified by
flash column chromatography eluting with EtOAc/hexanes (3:7) to
give 71 mg (52.0%) of 48 as a colorless liquid. NMR spectra (1H and
13C) were identical with reported literature values.
4.6. Experimental procedures for sequential CM/Evans aldol
reactions (Table 5)
4.6.1. Aldol 46. Hoveyda-Grubbs II (2) (15 mg, 0.024 mmol) was
added to a mixture of styrene (9) (50 mg, 0.480 mmol) and cro-
tonaldehyde (67 mg, 0.96 mmol) in deaerated CH2Cl2 (3.2 mL). The
reaction mixture was heated to 40 ꢀC under an Ar atmosphere for
12 h and cooled to rt. The solvent was concentrated under reduced
pressure and the residue was dried for 10 min. To propionimide 42
(112 mg, 0.481 mmol) in CH2Cl2 (2 mL) was added a 1.0 M solution
of Bu2BOTf (0.53 mL, 0.53 mmol) at 0 ꢀC over 5 min followed by
Et3N (68 mg, 0.674 mmol) and stirred for 30 min. After cooling the
reaction mixture to ꢁ78 ꢀC, the metathesis product from the
previous step in CH2Cl2 (2 mL) was added dropwise. The reaction
mixture was stirred for 1 h, warmed to 0 ꢀC, and stirred an addi-
tional hour. The reaction was quenched by dropwise addition of
pH 7 phosphate buffer/MeOH (1 mL:1.5 mL) and MeOH/30% aq
H2O2 (1 mL:0.5 mL). The reaction mixture was stirred for addi-
tional hour at 10 ꢀC, extracted with CH2Cl2 (3ꢂ10 mL), washed
with NaHCO3 (10 mL), brine (10 mL), and dried over Na2SO4. The
residue was purified by flash column chromatography eluting
with EtOAc/hexanes (3:7) to give 105 mg (60%) of 46 as a colorless
liquid. NMR spectra (1H and 13C) were identical with reported
literature values.
4.6.4. Aldol 49. Hoveyda-Grubbs II (2) (9 mg, 0.014 mmol) was
added to a mixture of PMB ether 45 (50 mg, 0.281 mmol) and
crotonaldehyde (40 mg, 0.562 mmol) in CH2Cl2 (2.0 mL) and dea-
erated for 5 min. The reaction mixture was heated to 40 ꢀC under an
Ar atmosphere for 12 h and cooled to rt, the solvent was concen-
trated under reduced pressure and the residue was dried for 10 min.
To a solution of propionimide 42 (66 mg, 0.281 mmol) in CH2Cl2
(2 mL) was added 1.0 M solution of Bu2BOTf (0.51 mL, 0.506 mmol)
at 0 ꢀC over 2 min followed by Et3N (57 mg, 0.562 mmol) and stir-
red for 1 h at 0 ꢀC and the metathesis product was added slowly
using CH2Cl2 (2 mL) and cooled to ꢁ45 ꢀC, stirred for 12 h and
quenched by adding pH 7 buffer (2 mL), MeOH (2 mL), and a mix-
ture of MeOH, 30% H2O2 (1þ0.5 mL). The reaction was stirred for
30 min at rt and extracted with CH2Cl2 (3ꢂ10 mL), washed with
NaHCO3 (10 mL), brine (10 mL), and dried over Na2SO4, purified by
flash column chromatography eluting with EtOAc/hexanes (3:7) to
give 79 mg (64% yield) of 49 as a colorless liquid. NMR spectra (1H
and 13C) were identical with reported literature values.
4.6.2. Aldol 47. Hoveyda-Grubbs II (2) (9 mg, 0.0145 mmol) was
added to a mixture of TBS ether 43 (50 mg, 0.29 mmol) and
crotonaldehyde (41 mg, 0.96 mmol) in deaerated CH2Cl2 (2 mL).
The reaction mixture was heated to 40 ꢀC under an Ar atmo-
sphere for 12 h and cooled to rt. The solvent was concentrated
under reduced pressure, and the residue was dried for 10 min
4.7. General procedure for sequential CM/Roush allylation
reactions (Table 6)
Hoveyda-Grubbs II (2) (5 mol %) was added to a mixture of CM
partner (1 equiv) and crotonaldehyde (2 equiv) in CH2Cl2 (0.15 M)
and deaerated for 5 min. The reaction mixture was heated to 40 ꢀC
under an Ar atmosphere for 12 h and cooled to rt, the solvent was
concentrated under reduced pressure, and the residue was filtered
through a plug of silica eluting with Et2O. The solvent was con-
centrated under reduced pressure and dried for 10 min. To a solu-
tion of (ꢁ)-DIPCl (2 equiv) in Et2O (2 mL) at 0 ꢀC was added a 1.0 M
solution of allylmagnesium bromide in Et2O (1.92 equiv). The re-
action mixture was warmed to rt and stirred for 1 h. After cooling
the reaction mixture to ꢁ78 ꢀC, a solution of enal from the CM was
slowly added over a period of 10 min using little ether (1 mL) and
stirred for 70 min. The reaction was quenched by adding MeOH and
allowed to rt, extracted with 1 N aq HCl solution. The combined
organic layers were basified using 30% NaOH solution to a pH of
12e13 and extracted with CH2Cl2 (3ꢂ10 mL), washed with NaHCO3
(10 mL), brine (10 mL), and dried over Na2SO4. Concentration of the
organics and purification of the residue by flash column chroma-
tography eluting with Et2O/toluene (1:9) gave the corresponding
under vacuum. To
a solution of propionimide 42 (68 mg,
0.29 mmol) in CH2Cl2 (3 mL) was added a 1.0 M solution of
Bu2BOTf (0.34 mL, 0.34 mmol) at 0 ꢀC over 5 min followed by
freshly distilled i-Pr2NEt (50 mg, 0.383 mmol) over 5 min and the
reaction mixture was cooled to ꢁ78 ꢀC. The above metathesis
product dissolved in CH2Cl2 (2 mL) was added to the reaction
mixture and stirred for 30 min after which the reaction vessel
was transferred to a ꢁ20 ꢀC freezer for 12 h. The solution was
placed in an ice bath and quenched with pH 7 phosphate buffer
(1 mL) followed by MeOH (3 mL). A mixture of MeOH (3 mL) and
30% H2O2 (1 mL) was added over 15 min and stirring was con-
tinued for 30 min at 0 ꢀC. The mixture was extracted with CH2Cl2
(3ꢂ10 mL), washed with NaHCO3 (10 mL), brine (10 mL), and
dried over Na2SO4. After concentrating the organics, the residue
was purified by flash column chromatography eluting with
EtOAc/hexanes (3:7) to give 60 mg (48% yield) of 47 as a colorless

2204
G. Sirasani et al. / Tetrahedron 67 (2011) 2197e2205
homoallylic alcohols, whose NMR spectra (1H and 13C) were iden-
tical with reported literature values. Mosher esters were prepared
from the homoallylic alcohols to determine % ee.37
2.43e2.41 (m, 1H), 0.89 (s, 3H), 0.87 (s, 9H), ꢁ0.02 (s, 3H), ꢁ0.22 (s,
3H); 13C NMR (100 MHz, CDCl3):
143.7, 141.1, 127.6, 126.9, 126.9,
114.4, 79.1, 46.4, 25.8, 18.2, 16.1, ꢁ4.6, ꢁ5.1; IR (neat): 2957, 2930,
2886, 2858, 1454, 1362, 1254, 1086, 1065, 910 cmꢁ1; HRMS (FAB)
calcd for C17H28OSiꢁHþ¼275.1831, found 275.1830.
d
4.8. General procedure for sequential CM/Roush crotylation
reactions (Table 6)
4.8.6. Compound 35. 1H NMR (400 MHz, CDCl3):
d 7.53e7.51 (m,
Hoveyda-Grubbs second-generation catalyst (5 mol %) was
added to a mixture of the terminal olefin (1 equiv) and crotonalde-
hyde (2 equiv) in deaerated CH2Cl2 (0.15 M). The reaction mixture
was heated to 40 ꢀC under an Ar atmosphere for 12 h and cooled to
rt. The solvent was concentrated under reduced pressure, and the
residue was filtered through a plug of silica eluting with Et2O. The
solvent was concentrated under reduced pressure and dried for
10 min. To an oven-dried round-bottomed flask equipped with
2H), 7.47e7.43 (m, 2H), 7.38e7.34 (m, 1H), 6.66 (d, J¼16.0 Hz, 1H),
6.33 (dd, J¼16.0, 6.5, 16 Hz, 1H), 6.07e5.99 (m, 1H), 5.23e5.18 (m,
2H), 4.19 (t, J¼5.2, 1.2 Hz, 1H), 2.53 (m, 1H), 1.20 (d, J¼6.8 Hz, 1H),
1.11 (s, 9H), 0.24 (s, 6H); 13C NMR (100 MHz, CDCl3):
d 140.8, 137.2,
131.4, 130.2, 128.5, 127.3, 126.4, 114.6, 45.1, 25.9, 18.3, 15.4, ꢁ4.1,
ꢁ4.8; IR (neat): 2957, 2929, 2886, 2857, 1252, 1065, 967 cmꢁ1
HRMS (FAB) calcd for C19H30OSiꢁHþ¼301.1989, found 301.1996.
;
4.8.7. Compound 36. 1H NMR (400 MHz, CDCl3):
d 7.35e7.26 (m,
ꢀ
magnetic stirbarand 4 A molecular sieves (100 mg per 1 mmol of the
reagent) was added a 1.0 M solution of Roush’s reagent 51 (1.5 equiv)
in toluene. The mixture was cooled to ꢁ78 ꢀC. The enal from the CM
reaction was added to the reagent and rinsed with toluene (1 mL).
The reaction mixture was stirred at ꢁ78 ꢀC for 5 h. The reaction was
quenched with dropwise addition of 2 N aq NaOH (1 mL), and the
mixture was warmed to 0 ꢀC. After stirring an additional 20 min at
0 ꢀC, the mixture was extracted with Et2O (3ꢂ10 mL), washed with
brine (10 mL), and dried over K2CO3. Concentration of the organics
and purification of the residue by flash column chromatography
eluting with EtOAc/hexanes (1:4) gave the corresponding homo-
allylic alcohols, whose NMR spectra (1H and 13C) were identical with
reported literature values. Mosher esters were prepared from the
homoallylic alcohols to determine % ee.37
5H), 5.76e5.65 (m, 2H), 4.54, 4.52 (ABq, J¼12.0 Hz, 2H), 4.08 (br s,
2H), 3.41e3.35 (m, 1H), 2.33e2.30 (m, 2H), 1.59e1.55 (m, 3H), 0.93
(t, J¼7.4 Hz, 3H); 13C NMR (100 MHz, CDCl3):
d 138.9, 131.4, 129.0,
128.3 (2C), 127.7 (2C), 127.5, 79.8, 70.9, 63.6, 36.1, 26.4, 9.6; IR
(neat): 3384, 2964, 2932, 2872, 1454, 1349, 1090, 1064, 1027, 1005,
972, 910 cmꢁ1; HRMS (FAB) calcd for C14H20O2þNa¼243.1361,
found 243.1351.
4.8.8. Compound 37. 1H NMR (400 MHz, CDCl3):
d 7.37e7.20 (m,
5H), 5.70e5.58 (m, 2H), 4.68 (dd, J¼7.0, 5.0 Hz, 1H), 4.05e4.04 (m,
2H), 2.50e2.35 (m, 2H), 1.39 (br s, 1H), 0.88 (s, 9H), 0.02 (s, 3H),
ꢁ0.13 (s, 3H); 13C NMR (100 MHz, CDCl3):
d 144.9, 131.5, 129.4, 128.0
(2C), 127.0, 125.8 (2C), 74.9, 63.7, 43.8, 25.8, 18.2e4.7, ꢁ4.9; IR
(neat): 3363, 2953, 2930, 2885, 2857, 1471, 1362, 1255, 1091, 1005,
909, 836 cmꢁ1; HRMS (FAB) calcd for C17H28O2SiþNa¼315.1756,
found 315.1750.
4.8.1. Compound 15. 1H NMR (400 MHz, CDCl3):
1H), 6.42e6.35 (m, 1H), 6.07e6.00 (m, 1H), 4.19 (q, J¼7.2 Hz, 2H),
3.67 (s, 3H), 2.50 (t, J¼6.4 Hz, 2H), 2.47e2.43 (m, 2H), 1.91 (s, 3H);
d
7.13 (d, J¼11.2 Hz,
13C NMR (100 MHz, CDCl3):
d
173.0, 168.4, 139.7, 137.8, 127.0, 126.2,
4.8.9. Compound 38. 1H NMR (400 MHz, CDCl3):
d 7.39e7.30 (m, 4H),
60.4, 51.6, 33.3, 28.3, 14.2, 12.5; IR (neat): 2982, 2953, 1739,
1703 cmꢁ1; HRMS (FAB) calcd for C12H18O4þHþ¼227.1283, found
227.1277.
7.26e7.23 (m, 1H), 6.52 (d, J¼16.0 Hz,1H), 6.20 (dd, J¼16.0, 6.4 Hz,1H),
5.74e5.71 (m, 2H), 4.36 (q, J¼6.0 Hz, 1H), 4.16e4.12 (m, 2H),
2.38e2.35 (m, 2H),1.50 (br s,1H), 0.95 (s, 9H), 0.12 (s, 3H), 0.10 (s, 3H);
13C NMR (100 MHz, CDCl3):
d 137.0, 132.7, 131.7, 129.3, 128.8, 128.5
4.8.2. Compound 19. 1H NMR (400 MHz, CDCl3):
d
7.15 (d,
(2C),127.4,126.4 (2C), 73.3, 63.6, 41.5, 25.9,18.3, ꢁ4.3, ꢁ4.7; IR (neat):
3356 cmꢁ1; IR (neat): 3356, 2953, 2929, 2893, 2856, 1471, 1253,1071,
968 cmꢁ1; HRMS (FAB) calcd for C19H30O2SiþNa¼341.1913, found
341.1904.
J¼11.2 Hz, 1H), 6.38e6.31 (m, 1H), 6.10e6.00 (m, 1H), 4.19 (q,
J¼7.2 Hz, 2H), 3.61 (t, J¼6.0 Hz, 2H), 2.25 (q, J¼7.2 Hz, 2H), 1.91 (s,
3H), 1.68e1.61 (m, 2H), 1.29 (t, J¼7.2 Hz, 3H), 0.89 (s, 9H), 0.04 (s,
6H); 13C NMR (100 MHz, CDCl3):
d 168.6, 142.4, 138.4, 126.3, 125.2,
62.2, 60.4, 32.0, 29.6, 25.9, 18.3, 14.3, 12.5, ꢁ5.3; IR (neat): 2953,
2930, 1706 cmꢁ1; HRMS (FAB) calcd for C17H32O3SiþHþ¼313.2199,
found 313.2210.
4.8.10. Compound 40. 1H NMR (400 MHz, CDCl3):
d 7.29e7.21 (m,
5H), 5.72e5.50 (m, 2H), 4.43 (d, J¼6.0 Hz, 1H), 4.06 (br s, 2H),
2.45e2.40 (m, 1H), 1.16 (br s, 1H), 0.89 (d, J¼3.6 Hz, 3H), 0.87 (s, 9H),
0.01 (s, 3H), ꢁ0.22 (s, 3H); 13C NMR (100 MHz, CDCl3):
d 143.6,135.3,
4.8.3. Compound 20. 1H NMR (400 MHz, CDCl3):
d
7.31 (d,
129.2, 127.6, 127.0, 126.9, 126.8, 79.1, 63.9, 45.1, 25.8, 18.2, 16.5, ꢁ4.6,
ꢁ5.1; IR (neat): 3333, 2955, 2929, 2885, 2856,1471,1455,1253,1088,
1064 cmꢁ1; HRMS (FAB) calcd for C18H30O2SiþNa¼329.1913, found
329.1923.
J¼15.6 Hz, 1H), 5.89 (t, J¼7.2 Hz, 1H), 5.78 (d, J¼15.6 Hz, 1H), 3.73 (s,
3H), 3.58 (t, J¼6.8 Hz, 2H), 2.26 (q, J¼8.0 Hz, 2H), 1.76 (s, 3H),
1.65e1.58 (m, 3H), 0.88 (s, 9H), 0.34 (m, 6H); 13C NMR (100 MHz,
CDCl3):
d 168.0, 149.8, 141.8, 133.1, 115.1, 62.3, 51.4, 32.1, 25.9, 25.2,
18.3, 12.0, ꢁ5.3; IR (neat): 2952, 2930, 1726 cmꢁ1; HRMS (FAB)
4.8.11. Compound 41. 1H NMR (400 MHz, CDCl3):
d 7.42e7.34 (m,
calcd for C16H30O3SiþHþ¼299.2043, found 299.2056.
4H), 7.30e7.26 (m, 1H), 6.53 (d, J¼16.0 Hz, 1H), 6.19 (dd, J¼16.0,
6.8 Hz, 1H), 5.80e5.68 (m, 2H), 4.19e4.16 (m, 3H), 2.44e2.38 (m,
1H), 1.43 (br s, 1H), 1.07 (d, J¼6.8 Hz, 3H), 0.96 (s, 9H), 0.12 (s, 3H),
4.8.4. Compound 32. 1H NMR (400 MHz, CDCl3):
d 7.46e7.44 (m,
2H), 7.40e7.37 (m, 2H), 7.32e7.29 (m, 1H), 6.61 (d, J¼16.0 Hz, 1H),
6.31 (dd, J¼16.0, 6.0 Hz, 1H), 5.99e5.89 (m, 1H), 5.20e5.13 (m, 2H),
4.44e4.39 (m, 1H), 2.51e2.37 (m, 2H), 1.03 (s, 9H), 0.19 (s, 3H), 0.16
0.08 (s, 3H); 13C NMR (100 MHz, CDCl3):
d 137.1, 135.0, 131.4, 130.3,
129.3, 128.5 (2C), 127.4, 126.4 (2C), 77.3, 63.8, 43.6, 25.9, 18.2, 15.8,
ꢁ4.2, ꢁ4.8; IR (neat): 3357, 2956, 2929, 2884, 2856, 1471, 1461,
(s, 3H); 13C NMR (100 MHz, CDCl3):
d
137.1,134.8,132.8,129.2,128.5,
1362, 1253, 1070, 969, 909 cmꢁ1
; HRMS (FAB) calcd for
127.3, 126.4, 117.0, 73.3, 43.2, 25.9, 18.3, ꢁ4.3, ꢁ4.7; IR (neat): 2955,
2930, 2895, 2856, 1472, 1361, 1254, 1071, 966, 910 cmꢁ1; HRMS
(FAB) calcd for C18H28OSiꢁHþ¼287.1831, found 287.1826.
C20H32O2SiþNa¼355.2069, found 355.2079.
Acknowledgements
4.8.5. Compound 34. 1H NMR (400 MHz, CDCl3):
5H), 5.88e5.79 (m, 1H), 4.98e4.89 (m, 2H), 4.45 (d, J¼6.0 Hz, 2H),
d
7.30e7.21 (m,
Financial support of this work by the Department of Chemistry
at Temple University is gratefully acknowledged. We thank Dr.

G. Sirasani et al. / Tetrahedron 67 (2011) 2197e2205
2205
20. Andrade, R. B.; Martin, S. F. Org. Lett. 2005, 7, 5733.
21. Still, W. C.; Gennari, C. Tetrahedron Lett. 1983, 24, 4405.
22. For a review of the SAE, see Johnson, R. A.; Sharpless, K. B. Catal. Asymmetric
Richard Pederson (Materia, Inc.) for a generous donation of Grubbs-
II (1) and Hoveyda-Grubbs-II (2) catalysts.
Synth. (2nd Ed.) 2000, 231.
23. Nagaoka, H.; Kishi, Y. Tetrahedron 1981, 37, 3873.
24. For examples see: Ref. 34.
References and notes
25. Taber has reported an alternative CM approach using (Z)-2-butene-1,4-diol as
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27. Enoate intermediates were isolated in separate experiments. Coupling con-
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28. For a review see: (a) Hoffmann, R. W. Angew. Chem., Int. Ed. Engl. 1982, 21, 555;
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