Synthesis of five-membered unsaturated compounds from ketones via cyanophosphates under neutral conditions: [1,5]-C–H insertion of alkylidene carbenes generated by tetrazole fragmentation

Article abstract of DOI:10.1016/j.tet.2017.08.054

Cyanophosphates (CPs) can easily be prepared via the reactions of carbonyl compounds with diethyl phosphorocyanidate (DEPC) in the presence of LiCN (cat.) under non-aqueous conditions. Treatment of ketone-derived CPs with TMSN₃/Bu₂Sn

Full text of DOI:10.1016/j.tet.2017.08.054

Accepted Manuscript
Synthesis of five-membered unsaturated compounds from ketones via
cyanophosphates under neutral conditions: [1,5]-C-H insertion of alkylidene carbenes
generated by tetrazole fragmentation
Hiroki Yoneyama, Kenji Uemura, Yoshihide Usami, Shinya Harusawa
PII:
S0040-4020(17)30895-5
10.1016/j.tet.2017.08.054
TET 28948
DOI:
Reference:
To appear in: Tetrahedron
Received Date: 19 July 2017
Revised Date: 23 August 2017
Accepted Date: 25 August 2017
Please cite this article as: Yoneyama H, Uemura K, Usami Y, Harusawa S, Synthesis of five-membered
unsaturated compounds from ketones via cyanophosphates under neutral conditions: [1,5]-C-H
insertion of alkylidene carbenes generated by tetrazole fragmentation, Tetrahedron (2017), doi: 10.1016/
j.tet.2017.08.054.
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ACCEPTED MANUSCRIPT
8/23/2017
Synthesis of five-membered unsaturated compounds from ketones via
cyanophosphates under neutral conditions: [1,5]-C_H insertion of
alkylidene carbenes generated by tetrazole fragmentation
Hiroki Yoneyama, Kenji Uemura, Yoshihide Usami, and Shinya Harusawa*
Osaka University of Pharmaceutical Sciences, 4-20-1 Nasahara, Takatsuki, Osaka
569-1094, Japan
E-mail: harusawa@gly.oups.ac.jp
Graphical Abstract
O
R3
H
R2
NC P(OEt)2
(DEPC)
R3
X
CN
R2
TMSN3
cat. Bu2SnO
H
X
R1
O
cat. LiCN
OP(OEt)2
O
R1
toluene, reflux
THF
R3
R2
R3
R2
H
[1,5] C-H insertion
C
X
X
R1
R1
1

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Abstract
Cyanophosphates (CPs) can easily be prepared via the reactions of carbonyl compounds
with diethyl phosphorocyanidate (DEPC) in the presence of LiCN (cat.) under
non-aqueous conditions. Treatment of ketone-derived CPs with TMSN3/Bu2SnO (cat.)
in toluene at reflux produces cyclopentenes or heterocyclic products in good yields
under neutral conditions. In this two-step transformation, CPs may form
tetrazolylphosphates, which subsequently undergo successive fragmentation to generate
alkylidene carbenes, which undergo [1,5]-C_H insertions to yield five membered
compounds.
Keywords
five-membered compound; ketone; cyanophosphate; neutral condition; [1,5]-C_H
insertion; alkylidene carbene.
2

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Alkylidene carbenes 1 undergo regio- and stereoselective intramolecular [1,5]-C_H
insertions, which that are well suited for the synthesis of cyclopentenes 2 (X = CH2)
(Scheme 1, eq. 1).1 In case a heteroatom is present in the connecting chain,
five-membered unsaturated heterocycles 2 (X = O or N-R) are produced. Alternatively,
[1,2]-migrations occurring with alkylidene carbenes 1 (R2 = H or Ar) are useful for the
preparation of homologous alkynes 3, a reaction of which is extensively utilized in
organic synthesis (eq. 2).2
Scheme 1. [1,5]-C_H insertion and [1,2]-migration reactions of alkylidene carbenes
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The high reactivity of alkylidene carbenes necessitates their in situ generation,
typically via the use of diazo olefination reagents, haloalkenes, or alkynyliodonium
salts.1 One of the most widely employed methods to access alkylidene carbenes is the
loss of N2 from a double bond terminus, from 1-diazoalkenes in particular. These
reactions employ dimethyl(diazomethyl)phosphonate esters [(MeO)2P(O)CHN2:
DAMP] (Seyferth-Gilbert reagent)3 or trimethylsilyldiazomethane (TMSCHN2),4,5
which require strong basic conditions as a potential drawback.1,2
On the other hand, the use of tetrazoles to produce alkylidene carbenes under
base-free conditions is also known.1a It is necessary to generate alkylidene carbenes in
situ from more stable precursors. In 1966, Behringer and Matner first reported that
tetrazole derivatives 4 gave alkylidene carbenes 1 via the fragmentation of unstable
tetraazafulvenes 5, producing alkynes 3 (Scheme 2).6
Scheme 2. Fragmentation of tetraazafulvenes first reported by Behringer
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Wardrop and Komenda recently reported synthetic methods for alkynes 3 or five
membered rings 2 from carbonyl compounds 6 in three steps by the generation of
alkylidene carbenes 1 accessed through the dehydration of 5-hydroxy-1H-tetrazoles 4a
with diisopropylcarbodiimide (DIC) (Scheme 3).7
Scheme 3. Dehydrative fragmentation of 5-hydroxy-1H-tetrazoles reported by
Wardrop
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Meanwhile, Van Nhien and Postel8 reported a method for the generation of alkylidene
carbenes based on the reaction of cyanohydrin O-mesylates (cyanomesylates) with
trimethylsilylazide (TMSN3)/Bu2SnO (Wittenberger’s method).9 As an example
described (Scheme 4), cyanomesylate 9, which was prepared from sugar template 8 in
three steps containing an aqueous condition, was converted into dihydrofuran derivative
8b
10 through the [1,5]-C−H bond insertion of an alkylidene carbene in a modest yield.
However, the scope and limitations of this method have been not clarified.
Scheme 4. Generation of alkylidene carbenes based on the reaction of cyanomesylates
Ph
O
Ph
O
1) PCC, 18 h
2) KCN, NaHCO3
H2O - CH2Cl2, 60 h
O
O
O
O
MsO
NC
HO
OBn
OBn
3) MsCl, 52 h
OBn
OBn
8
9 (14%)
Ph
O
Ph
O
TMSN3
O
C
O
O
[1,5]
O
cat. Bu2SnO
OBn
OBn
toluene
reflux, 18 h
O
O
Ph
10
Ph
(22%)
6

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On the other hand, treatment of a range of carbonyl compounds 6 with diethyl
phosphorocyanidate (DEPC)10 in the presence of a catalyst easily affords
cyanohydrin-O-phosphates 11 (cyanophosphates, CPs) under non-aqueous conditions.11
CPs have been widely utilized as useful synthetic intermediates in organic synthesis.10
As part of our ongoing studies on the synthetic applications of CPs, we recently
demonstrated the efficient transformation of carbonyl compounds 6 into homologous
alkynes
3
under neutral conditions by the fragmentation of presumed
tetrazolylphosphates 12 derived from CPs 11 (Scheme 5, eq. 1).12 This reaction could be
extended to the formation of various alkynes that are not usually accessible from
carbonyl compounds via Ohira-Bestmann3d,e or Shioiri procedures4,5 under basic
conditions. The facile generation of the alkylidene carbenes from CPs prompted us to
investigate the [1,5]-C_H bond insertion expected in some cases. Herein, we report the
efficient and practical synthesis of a variety of five-membered unsaturated carbocyclic
or heterocyclic compounds 2 from carbonyl compounds 6 via CPs 11 under neutral
conditions, as shown in eq. 2 of Scheme 5.
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Scheme 5. Synthesis of five-membered unsaturated compounds from ketones via CPs
1. Synthesis of five-membered unsaturated compounds
We initially investigated the synthesis of cyclopentene 2a from CP 11a, which is
routinely prepared via treatment of 1-phenylheptan-3-one with DEPC (1.2 equiv.) in the
presence of LiCN (0.6 equiv.) in 92% yield.11,12 In a previous study on alkyne synthesis,
o
we found that solvents with boiling points >100 C may be necessary for the efficient
8

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generation of alkylidene carbenes from CPs.12 Accordingly, when CP 11a was treated
with TMSN3 (1.0 equiv.) in the presence of Bu2SnO (0.1 equiv.) at reflux for 2 h in
toluene (Table 1, entry 1), cyclopentene 2a was obtained as the major product in 42%
yield, together with alkyne 3a (18%). Alkyl-substituted alkylidene carbenes generally
undergo [1,5]-C_H insertions rather [1,2]-migrations.1 Prolongation of the reaction time
in toluene improved the yield of 2a (48%, entry 2), while the reactions at reflux in
o
xylene or cyclopentyl methyl ether (CPME: bp = 106 C) gave modest yields of 2a,
together with small amounts of 3a (entries 3 and 4). Reactions performed in benzene or
acetonitrile gave lower yields of 2a (entries 5 and 6).
Table 1. Formation of cyclopentene 2a from 11a in various solvents
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In the case of dialkyl ketone CP like 11a, competitive reactions between the insertion
and migration of carbene 1a take place. Methyl alkyl ketones 6 with lower migratory
aptitudes13 were therefore chosen as substrates for the formation of various five
membered compounds, as summarized in Table 2. Cyanophosphorylation of methyl
ketones 6b-g provided CPs 11b-g in 82% to 99% yields. Thus, CPs 11b-g could be
transformed into the corresponding five-membered compounds 2b-g in moderate to
high yields using TMSN3-Bu2SnO (cat.) in toluene at reflux (Table 2). In the case of
methyl ketones 6b-e (entries 1-4), cyclopentene 2b, 2,5-dihydrofuran 2c,
2,5-dihydropyrroles 2d, and 2e were readily obtained in 66%, 59%, 75%, and 74%
overall yields in two steps. Meanwhile, the respective overall yields of 2b-2e obtained
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via the Wardrop method were are lower 23%, 43%, 43%, and 49% in three-steps from
ketones 6b-e (see values in parenthesis of the right column of entries 1-4).7 In the
formation of 4-azaspiro[2.4]heptane 2f from cyclopropylbenzenesulfonamide 6f, a
significant amount of [1,2]-rearrangement product 3f was produced as an inseparable
mixture with 2f and alkyne 3f (54% overall yield from 6f, 2f/3f = 4/5), which was
similar to the results obtained via Wardrop method (38% overall yield from 6f, 2f/3f =
5/4) (entry 5).7 Furthermore, the present method was successfully applied to the
conversion
of
(4S)-2,2-dimethyl-4-(3-oxobutyl)-1,3-dioxolane
(6g)
into
spiro[4.4]nonene 2g (89% overall yield) (entry 6), which is a versatile intermediate in
the total synthesis of (-)-malyngolide14a or (-)-frontalin14b as reported by Ohira and
co-workers.14 They employed Shioiri conditions (TMSCHN2/n-BuLi)4 or the
Seyferth-Gilbert procedure (DAMP/t-BuOK)3a-c for the preparation of 2g from ketone
6g, to obtain the product in 73% and 68 % yields, respectively. The results summarized
in Table 2 indicate that our method is preferable to the existing methods.
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Table 2. Transformation of methyl alkyl ketones 6 into five-membered products 2 via
CPs 11
12

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13

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14

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Shioiri and co-workers reported that alkylidene carbenes generated from
β-trimethylsiloxy ketones underwent [1,5]-O_SiMe3 bond insertions to produce
5-trimethylsilyl-2,3-dihydrofurans.4c The present method could be used to similarly
generate 5-trialkylsilyl-2,3-dihydrofurans 2h (77 %) and 2i (81%) from the
corresponding CPs 11h (R= TMS) and 11i (R= TBDMS) (Scheme 6).
Scheme 6. Formation of 5-trialkylsilyl-2,3-dihydrofurans 2h and 2i using the present
method
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Furthermore, 16-membered cyclic ketone 13 yielded bicyclo[11.2.1]heptadecene 15
(59%) via CP 14 together with cyclic alkyne homolog 16 (16%), in which [1,5]-C–H
insertion mediated by alkylidene carbene from CP 14 was preferred to the formation of
cyclic alkyne homolog 15, as shown in eq 1 of Scheme 7.15 In contrast, Lee and
co-workers reported that reaction of small- to medium-sized cyclic ketones 13 (n = 4 -
14) with TMSC(Li)N2 led to allenylsilanes 17 (10 - 81%)(eq 2).16
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Scheme 7. Transformation of cyclic ketone 13 into bicyclic compound 15
Notably, β-keto ester 18, which possesses readily enolizable α-protons, could be
converted into cyclopentenyl acetate 20 in 95% overall yield using the present method
(Scheme 8, eq 1). In contrast, the reaction of 18 under Shioiri conditions
(TMSCH2/LDA) only resulted in unreacted starting material 18 (eq 2).4
17

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Scheme 8. Transformation of β-keto ester 18 into cyclopentenyl acetate 20
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Lee and co-workers reported that the reaction of a dienyl ketone 21 with
TMSC(Li)N2 produced linearly fused triquinones 22 and 23 (54%, 22/23 = 3/1)
(Scheme 9, eq. 2).17 This reaction can be rationalized in that alkylidene carbene 24
undergoes an intramolecular [2+1] cycloaddition with the tethered alkene to generate
methylenecyclopropane 25, and the fragmentation of this strained ring system provides
trimethylenemethane diyls 26a and 26b, which afford linearly fused triquinanes 22 and
23 through intramolecular [2+3] cycloaddition reactions, as described by Lee (Scheme 9,
eq. 2).17 Alternatively, cyanophosphorylation of dienyl ketone 21 followed by
treatment of the CP with TMSN3/Bu2SnO (cat.) affords triquinanes 22 and 23 in 61%
overall yield with the same ratio (22/23 = 3/1) (eq. 1).
19

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Scheme 9. Transformation of dienyl ketone 21 into triquinanes 22 and 23 using the
present method
20

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In conclusion, a novel two-step transformation of ketones into five-membered
unsaturated carbocycles or heterocyclic systems was developed. Under neutral
conditions, CPs react with TMSN3/Bu2SnO (cat.) to form putative tetrazoylphosphates,
which subsequently undergo successive fragmentation via [1,5]-C_H insertions to give
five-membered compounds. The present transformation is practical and provides
numerous functional motifs, such as cyclopentenes, 2,5-dihydrofurans,
2,5-dihydropyrrolidines,
4-azaspiro[2.4]heptane,
spiro[4.4]nonene,
5-trialkylsilyl-2,3-dihydrofurans, bicyclo[11.2.1]heptadecane, cyclopentenyl acetate,
and triquinanes. Where comparisons with the existing methods are possible, the same
products are generally observed, but in better yields. Such examples demonstrate the
superiority of this method over the Wardrop method, which uses tetrazol fragmentation,
or Shioiri method, which requires basic conditions. In addition, the present study also
contributes to the diversity of CPs as important intermediates in a variety of organic
syntheses.
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2. Experimental
2.1. General information
All reactions were carried out under an inert argon atmosphere. Anhydrous solvents
(tetrahydrofuran and toluene) were purchased from WAKO Chemical Company. During
organic workup, solvent extracts were dried over Na2SO4 and subsequently removed via
a rotary evaporator under reduced pressure. Fuji Silysia FL-60D silica gel was used for
flash column chromatography. Thin layer chromatography (TLC) was performed using
precoated plates (WAKO silica gel 70 F254). 1H-NMR spectra were recorded on a Varian
Mercury-300 or Agilent 400-MR-DD2 spectrometer in CDCl3 with tetramethylsilane
(TMS) as the internal standard. Coupling constants (J) are reported in Hertz (Hz). For
multiplicities, the following abbreviations were used: s, singlet; d, doublet; t, triplet; q,
quartet; m, multiplet; br, broad. 13C-NMR spectra were recorded on a Varian
Mercury-300 or Agilent 400-MR-DD2 spectrometer in CDCl3, chemical shifts (δ) are
given from CDCl3 (77.0 ppm). High-resolution mass spectra were obtained using a
JMS-700(2) double-focusing magnetic sector mass spectrometer (JEOL Ltd., Tokyo,
Japan) operated in positive-ion mode, with 3-nitrobenzyl alcohol (NBA) or
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triethanolamine (TEOA)-NaCl as the matrix.18
2.2. General procedure for synthesis of CPs 11
DEPC (196 mg, 1.2 mmol) and LiCN (20 mg, 0.6 mmol) were added to a solution of the
ketone (6, 1 mmol) in THF (5 mL) at rt. After stirring for 30 min, the reaction mixture
was treated with water (50 mL), extracted with EtOAc-hexane (1:1, 75 mL), washed
with brine, dried over Na2SO4, filtered, and concentrated. Purification by silica gel
column chromatography (EtOAc-hexane, 1:4) afforded CP 11.
2.2.1. 3-Cyano-1-phenylhept-3-yl diethyl phosphate 11a
1
Yield: 95%, colorless oil. H-NMR (300 MHz, CDCl3) δ 7.20-7.33 (m, 5H), 4.15-4.25
(m, 4H), 2.79-2.97 (m, 2H), 1.98-2.40 (m, 4H), 1.34-1.61 (m, 8H), 0.94 (t, J = 7.2 Hz,
3H); 13C-NMR (75.5 MHz, CDCl3) δ 13.8, 16.0, 16.1, 22.3, 26.0, 30.2, 38.5, 40.6, 64.5
(64.45), 64.5 (64.53), 78.4, 78.5, 118.0, 126.4, 128.4, 128.6, 139.9; HRMS (EI): m/z
calcd for C18H29NO4P [M+H]+ 354.1834, found 354.1834.
2.2.2. 2-Cyanoundec-2-yl diethyl phosphate 11b
1
Yield: 96%, colorless oil. H-NMR (400 MHz, CDCl3) δ 4.13-4.23 (m, 4H), 1.99-2.07
23

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(m, 1H), 1.85-1.93 (m, 1H), 1.84 (s, 3H), 1.46-1.62 (m, 2H), 1.22-1.40 (m, 18H), 0.88 (t,
J = 6.8 Hz, 3H); 13C-NMR (100 MHz, CDCl3) δ 14.0, 15.9, 16.0, 22.6, 24.0,
26.3(26.30), 26.3(26.33), 29.0, 29.2, 29.3, 29.4, 31.8, 41.4(41.37), 41.4(41.43),
64.3(64.27), 64.3(64.40), 74.9, 75.0, 118.8(118.78), 118.8(118.82); HRMS (EI): m/z
calcd for C16H33NO4P [M]+ 334.2102, found 334.2140.
2.2.3. 1-Benzyloxy-2-cyanoprop-2-yl diethyl phosphate 11c
Yield: 82%, colorless oil. 1H-NMR (400 MHz, CDCl3) δ 7.27-7.38 (m, 5H), 4.69 (d, J =
12.0 Hz, 1H), 4.64 (d, J = 12.0 Hz, 1H), 4.11-4.21 (m, 4H), 3.83 (d, J = 10.0 Hz, 1H),
13
3.69 (dd, J = 10.0, 0.8 Hz, 1H), 1.85 (s, 3H), 1.31-1.37 (m, 6H); C-NMR (100 MHz,
CDCl3) δ 15.9, 16.0(15.97), 16.0(15.98), 23.7(23.68), 23.7(23.71), 64.6(64.56),
64.6(64.62), 73.6, 73.7, 73.8(73.79), 73.8(73.83), 73.9, 117.9(117.85), 117.9(117.89),
127.7, 128.2, 128.5, 136.9; HRMS (EI): m/z calcd for C15H23NO5P [M]+ 328.1269,
found 328.1312.
2.2.4. 2-Cyano-1-[N-(3,4-dimethoxybenzyl)phenylsulfonamido]propan-2-yl diethyl
phosphate 11d
1
Yield: 99%, colorless oil. H-NMR (300 MHz, CDCl3) δ 7.89 (d, J = 7.2 Hz, 2H),
24

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7.51-7.66 (m, 3H), 6.70 (d, J = 8.1 Hz, 1H), 6.58 (dd, J = 8.1, 1.8 Hz, 1H), 6.48 (d, J =
1.8 Hz, 1H), 4.60 (d, J = 15.6 Hz, 1H), 4.53 (d, J = 15.6 Hz, 1H), 4.08-4.22(m, 4H),
3.84 (s, 3H), 3.81 (dd, J = 15.6, 1.5 Hz, 1H), 3.67 (dd, J = 15.6, 1.5 Hz, 1H), 3.66 (s,
13
3H), 1.90 (s, 3H), 1.31-1.38 (m, 6H); C-NMR (75.5 MHz, CDCl3) δ 15.9, 16.0, 24.3,
51.7, 53.2, 55.8, 64.6, 64.7, 73.9, 74.1, 77.2, 110.8, 111.7, 118.1, 121.7, 126.3, 127.4,
129.3, 133.0, 140.2, 148.8, 149.0; HRMS (EI): m/z calcd for C23H31N2O8PS [M]+
526.1539, found 526.1541.
2.2.5. 2-Cyano-1-[N-(3,4-dimethoxyphenethyl)phenylsulfonamido]propan-2-yl diethyl
phosphate 11e
1
Yield: 95%, colorless oil. H-NMR (300 MHz, CDCl3) δ 7.84 (d, J = 6.9 Hz, 2H),
7.52-7.67 (m, 3H), 6.65-6.78 (m, 3H), 4.10-4.28 (m, 5H), 3.72-3.92 (m, 7H), 3.38-3.45
(m, 2H), 2.82-2.92 (m, 2H), 1.98 (s, 3H), 1.33-1.40 (m, 6H); 13C-NMR (75.5 MHz,
CDCl3) δ 16.0, 16.1, 24.1, 34.7, 52.4, 55.8, 56.4(56.36), 65.4(56.44), 64.8, 64.9, 65.0,
73.8, 73.9, 77.2, 111.2, 112.0, 118.0, 120.7, 127.3, 129.4, 130.4, 133.2, 138.7, 147.6,
148.9; HRMS (EI): m/z calcd for C24H33N2O8PS [M]+ 540.1695, found 540.1691.
2.2.6. 2-Cyano-1-(N-cyclopropylphenylsulfonamido)propan-2-yl diethyl phosphate 11f
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1
Yield: 85%, colorless oil. H-NMR (400 MHz, CDCl3) δ 7.82-7.87 (m, 2H), 7.60-7.65
(m, 1H), 7.51-7.57 (m, 2H), 4.16-4.26 (m, 4H), 3.90 (d, J = 14.8 Hz, 1H), 3.76 (d, J =
14.8 Hz, 1H), 2.29-2.36 (m, 1H), 1.98 (s, 3H), 1.36-1.41 (m, 6H), 0.69-0.88 (m, 4H);
13C-NMR (100 MHz, CDCl3) δ 8.3, 8.4, 15.9, 16.0, 24.8 (24.78), 24.8 (24.81), 31.7,
57.7, 57.8, 64.6, 64.7(64.67), 64.7(64.70), 64.8, 73.2, 73.3, 118.1, 118.2, 127.6, 129.0,
133.1, 139.0; HRMS (EI): m/z calcd for C17H26N2O6PS [M]+ 417.1249, found 417.1245.
2.2.7. 2-Cyano-4-[(S)-2,2-dimethyl-1,3-dioxolan-4-yl]butan-2-yl diethyl phosphate 11g
1
Yield: 97%, colorless oil. H-NMR (400 MHz, CDCl3) δ 4.05-4.24 (m, 6H), 3.56-3.62
(m, 1H), 1.87 (s, 3H), 1.70-2.28 (m, 4H), 1.42 (s, 3H), 1.35 (s, 3H), 1.24-1.48 (m, 6H);
13C-NMR (100 MHz, CDCl3) δ 16.0(15.96), 16.0(16.03), 25.5(25.47), 25.5(25.51),
26.4(26.35), 26.4(26.38), 26.5(26.45), 26.5(26.48), 26.9(26.86), 26.9(26.88), 28.2, 28.5,
28.6(28.58), 28.6(28.62), 37.8(27.78), 37.8(37.84), 37.9, 38.0, 64.4, 64.5(64.47),
64.5(64.53), 69.0, 69.1, 74.3, 74.4, 74.6, 74.8, 74.9, 77.5, 109.2, 118.4(118.39),
118.4(118.43), 118.5(118.49), 118.5(118.54); HRMS (EI): m/z calcd for C14H27NO6P
[M]+ 336.1576, found 335.1574.
2.2.8. 2-Cyano-4-phenyl-4-[(trimethylsilyl)oxy]butan-2-yl diethyl phosphate 11h
26

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Yield: 90%, colorless oil. 1H-NMR (300 MHz, CDCl3) δ 7.22-7.34 (m, 5H), 5.03 (dd, J
= 8.1, 3.9 Hz, 0.7H), 4.93 (dd, J = 9.3, 3.0 Hz, 0.3H), 4.09-4.24 (m, 4H), 2.18-2.58 (m,
2H), 1.93 (s, 2.1H), 1.90 (s, 0.9H), 1.32-1.40 (m, 6H), 0.01 (s, 6.3H), -0.03 (s, 2.7H);
13C-NMR (75.5 MHz, CDCl3) δ -0.1, -0.0, 15.9, 16.0, 26.1, 28.1, 50.1(50.06),
50.1(50.13), 51.0(50.96), 51.0(51.02), 64.3(64.27), 64.3(64.34), 64.4, 70.9, 71.1, 73.1,
73.2, 118.6(118.56), 118.6(118.63), 118.9, 125.9, 126.1, 127.7, 127.9, 128.4(128.35),
128.4(128.38), 143.4, 143.7; HRMS (EI): m/z calcd for C17H30N2O5PSi [M]+ 401.1662,
found 401.1668.
2.2.9. 4-[(tert-Butyldimethylsilyl)oxy]-2-cyano-4-phenylbutan-2-yl diethyl phosphate
11i
Yield: 97%, colorless oil. 1H-NMR (300 MHz, CDCl3) δ 7.24-7.34 (m, 5H), 5.03 (dd, J
= 8.7, 3.3 Hz, 0.3H), 4.94 (dd, J = 7.8, 4.2 Hz, 0.7H), 4.08-4.39 (m, 4H), 2.57 (dd, J =
14.4, 7.8 Hz, 0.6H), 2.24-2.40 (m, 1.4H), 1.96 (s, 0.9H), 1.88 (s, 2.1H), 1.32-1.48 (m,
13
6H), 0.86 (s, 9H), 0.11 (s, 0.9H), 0.06 (s, 2.1H), -0.30 (s, 3H); C-NMR (75.5 MHz,
CDCl3) δ -5.0, -4.9, -4.5(-4.50), -4.5(-4.48), 16.0, 16.1, 17.9, 18.0, 25.8, 25.9, 26.4, 28.0,
50.5, 50.6, 51.3, 51.4, 64.4(64.36), 64.4(64.42), 71.4, 71.6, 73.0, 73.1, 73.4, 73.5, 118.6,
118.7, 118.8(118.78), 118.8(118.83), 126.1, 126.4, 127.7, 128.0, 128.4, 143.6, 144.2;
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ACCEPTED MANUSCRIPT
HRMS (FAB): m/z calcd for C21H37NO5PSi [M+H]+ 442.2179, found 442.2179.
2.3. General procedure for the five-membered products 2
TMSN3 (116 mg, 1.0 mmol) and Bu2SnO (25 mg, 0.1 mmol) were added to a solution of
CP 11 (1.0 mmol) in toluene. After refluxing for 2 h, the reaction mixture was
evaporated to give a residue, which was purified by silica gel column chromatography
to give a five-membered product 2.
2.3.1. 2-(3-Methylcyclopent-1-en-1-yl)ethylbenzene 2a and oct-3-yn-1-ylbenzene 3a
Date for 2a: Yield: 42%, colorless oil. 1H-NMR (400 MHz, CDCl3) δ 7.25-7.29 (m, 2H),
7.15-7.20 (m, 3H), 5.26-5.27 (m, 1H), 2.67-2.78 (m, 2H), 2.20-2.34 (m, 3H), 2.02-2.14
13
(m, 1H), 1.30-1.40 (m, 1H), 0.96-1.00 (m, 3H); C-NMR (100 MHz, CDCl3) δ 21.3,
32.5, 33.1, 34.3, 34.9, 39.9, 125.7, 128.2, 128.3, 130.1, 142.5, 143.3; HRMS (EI): m/z
calcd for C14H18 [M]+ 186.1409, found 186.1407.
3a: Yield: 18%, colorless oil. 1H-NMR (400 MHz, CDCl3) δ 7.18-7.31 (m, 5H), 2.80 (t,
J = 7.6 Hz, 2H), 2.44 (tt, J = 7.6, 2.4 Hz, 2H), 2.14 (tt, J = 6.8, 2.4 Hz, 2H), 1.32-1.49
(m, 4H), 0.90 (t, J = 7.2 Hz, 3H); 13C-NMR (100 MHz, CDCl3) δ 13.6, 18.4, 21.0, 21.9,
31.1, 79.4, 81.0, 126.1, 128.3, 128.5, 141.0; HRMS (EI): m/z calcd for C14H18 [M]+
28

ACCEPTED MANUSCRIPT
186.1409, found 186.1409.
2.3.2. 3-Hexyl-1-methylcyclopent-1-ene 2b
1
Yield: 69%, colorless oil. H-NMR (300 MHz, CDCl3) δ 5.26-5.28 (m, 1H), 2.55-2.63
(m, 1H), 1.99-2.22 (m, 3H), 1.71 (s, 3H), 1.21-1.46 (m, 11H), 0.88 (t, J = 6.6 Hz, 3H);
13C-NMR (75.5 MHz, CDCl3) δ 14.4, 16.7, 22.7, 28.0, 29.6, 30.9, 32.0, 36.3, 36.6, 45.9,
129.2(129.17), 129.2(129.21), 139.8.
2.3.3. 4-Methyl-2-phenyl-2,5-dihydrofuran 2c
1
Yield: 72%, colorless oil. H-NMR (400 MHz, CDCl3) δ 7.24-7.36 (m, 5H), 5.75-5.78
(m, 1H), 5.49-5.52 (m, 1H), 4.70-4.75 (m, 1H), 4.60-4.64 (m, 1H), 1.82 (s, 3H);
13C-NMR (100 MHz, CDCl3) δ 12.2, 78.5, 88.5, 124.0, 126.3, 127.6, 128.4, 136.4,
142.6.
2.3.4. 1-Benzensulfonyl-2-(3,4-dimethoxyphenyl)-4-methyl-2,5-dihydro-1H-pyrrole 2d
1
Yield: 76%, colorless oil. H-NMR (300 MHz, CDCl3) δ 7.46-7.56 (m, 3H), 7.34-7.38
(m, 2H), 6.79 (dd, J = 8.1, 1.8 Hz, 1H), 6.75 (d, J = 8.1 Hz, 1H), 6.60 (d, J = 1.8 Hz,
1H), 5.48-5.55 (m, 1H), 5.26-5.28 (m, 1H), 4.24 (d, J = 13.5 Hz, 1H); 4.13 (dd, J = 13.5,
29