Synthetic scope, computational chemistry and mechanism of a base induced 5-endo cyclization of benzyl alkynyl sulfides

Abstract

We present an experimental and computational study of the reaction of aryl substituted benzyl 1-alkynyl sulfides with potassium alkoxide in acetonitrile, which produces 2-aryl 2,3-dihydrothiophenes in poor to good yields. The cyclization is most efficient with electron withdrawing groups on the aromatic ring. Evidence indicates there is rapid exchange of protons and tautomerism of the alkynyl unit prior to cyclization. Theoretical calculations were also conducted to help rationalize the base induced 5-endo cyclization of benzyl 1-propynyl sulfide (1a). The potential energy surface was calculated for the formation of 2,3-dihydrothiophene in a reaction of benzyl 1-propynyl sulfide (1a) with potassium methoxide. Geometries were optimized with CAM-B3LYP/6-311+G(d,p) in acetonitrile with the CPCM solvent model. It is significant that the benzyl propa-1,2-dien-1-yl sulfane (6) possessed a lower benzylic proton affinity than the benzyl prop-2-yn-1-yl sulfane (8) thus favoring the base induced reaction of the former. From benzyl(propa-1,2-dien-1-yl sulfane (6), 2,3-dihydrothiophene can be formed via a conjugate base that undergoes 5-endo-trig cyclization followed by a protonation step.

1. Introduction

2,3-Dihydrothiophenes are useful synthetic precursors for many compounds including thiophenes,¹ thionucleoside derivatives² and penicillin mimics.³ Synthetic routes to 2,3-dihydrothiophenes are varied and numerous,^1f,4 with based-induced cyclizations playing an important role. Under basic conditions, starting substrates usually require the presence of electron withdrawing or other functionality to facilitate condensation chemistry or to directly participate in the cyclization.⁵ Some cyclizations that make use of transition metals to target dihydrothiophenes⁶ do not require such strong directing functionality.^6a A radical based cyclization free of strong electron withdrawing groups provided mixtures of 2,3 and 2,5-dihydrothiophenes.⁷

In 2000, the Schwan group reported chemistry that created 2,3-dihydrothiophenes (2) by way of a t-butoxide induced 5-endo cyclization of 2-substituted arylmethyl alkynyl sulfides, eq. (1).⁸ That reaction was thought to involve benzylic deprotonation and cyclization at the terminal carbon of the propynyl chain, even though the starting material did not possess unsaturation in the terminal carbon, nor held any other skeletal functionality to bring about carbon-carbon bond formation. Although there was no ostensible need for strong electron withdrawing groups or other reactive functionality in the substrates, there nevertheless was a requirement for an electron withdrawing group on the aryl ring. In the communication, some mechanistic data was offered, but some intriguing uncertainties remained.⁸ How was it that the cyclization occurred most efficiently when the starting material did not have unsaturation at the propynyl terminus? Which tautomeric form of the 3-carbon unit is accepting the electron density? We now report that a broader selection of arylmethyl alkynyl sulfides succumbs to the cyclization and we offer some mechanistic and computational evidence concerning the mode of cyclization of the substrates.

(1)

2. Results and Discussion

2.1. Scope of the reaction

The requisite starting materials (1) were accessible by adaption of benzylic halides or alcohols. The alcohols were converted to thiocyanates under Mitsunobu conditions, whereas the halides were converted to thiocyanates or thiotosylates by direct substitution with appropriate sulfur reagent.⁹ The ArCH₂S-X reagents were then treated with an acetylide to bring forth the benzylic alkynyl sulfides.¹⁰ Full synthetic procedures are in the Supporting Information.

In the communication,⁸ many optimized reaction parameters were reported including solvent and substrate concentration. It was subsequently learned that KOtBu is preferred over sodium or lithium t-butoxide. Thus, treating the starting sulfides 1 with 2 eq. of KOtBu in acetonitrile at various temperatures for 24 hours affords a dihydrothiophene (2) with the aryl group at the 2-position and the double bond at the 4 position, eq. (1).

The products and yields are outlined in Table 1. The products were identified through standard spectroscopic characterization. Particularly diagnostic are the five sets of nonaryl resonances in the ¹H NMR spectrum, each of which represents one proton from the dihydrothiophene ring. The ¹H NMR spectra consistently exhibit a ddd near 6.2 ppm, a dt near 5.6 ppm, a dd near 5.3 ppm, a ddt near 3.3 ppm and a dddd near 2.9 ppm. The ¹H-¹H coupling constants of products match those of related heterocycles.^5c,11 The initial notion that a 2-substituted aryl group is required for cyclization⁸ was found to be invalid, as the results show that electron withdrawing groups at other aryl position promote the reaction.

Table 1.

Cyclization data for benzyl 1-alkynyl sulfides.

#	Product	temp. (°C)a	Yieldb
2a	X = 2-H	reflux	28c,d
b	X = 2-I	0	75
c	X = 2-Br	0	74
d	X = 2-Cl	0	74
e	X = 2-Me	reflux	0
f	X = 2-Ph	reflux e	41c,d
g	X = 2-F	reflux	45
h	X = 2-CN	reflux	64
i	X = 3-I	rt	68
j	X = 4-I	rt	45
k	X = 3-CF3	reflux	59
l	X = 2-SPh	reflux	66
m	X = 2-S(O)Ph	reflux	45f
n	X = 2-S(O)2Ph	reflux	68
o	X = 2,5-(OMe)2	reflux	44c,d
p	X = 3,5-(OMe)2	reflux	54c
q	X = 3-NO2	reflux	0
r	X = 2-NO2	reflux	0
s		0	72
t		60 f,g	47
u		0	69h

^aReaction temperature. Compounds 1 were stirred for 24 h. unless otherwise indicated.

^bYield is of isolated material unless otherwise indicated.

^cYield based on consumed starting material.

^dProduct could not be separated from starting material. Product was assigned based in the characteristic ¹H NMR peaks.

^eRefluxed for 8 h.

^f1:1 mixture of diastereomers.

^gRefluxed for 6 h.

^hRatio of isomers based on double bond position: 2,3/2,5 = 1/1.7

The presence of the nitro groups prevented the reaction and starting material as fully recoverable in the 2-nitro case (1r) whereas full decomposition occurred in the 3-nitro case (1q). Replacing the aryl groups with heteroaryl groups prevented the reaction. Specifically, 2-bromothien-3-ylmethyl 1-propynyl sulfide, 2-furfuryl 1-propynyl sulfide and 2-fluoro-4-iodopyrid-3-yl 1-propynyl sulfide did not cyclize. Also, positioning an iodine group at the peri position did not prompt cyclization of 8-iodonaphthalen-1-ylmethyl 1-propynyl sulfide.

A selection of dihydrothiophenes has been shown to be oxidizable to thiophenes.1c,1e–g^,12 Accordingly, we have achieved the successful conversion of heterocycles 2b and 2h into thiophenes 3b and 3h in 73 and 81% yields respectively, with DDQ^1e in CHCl₃. Moreover the additional functionality on the aryl unit provides a reactive feature for further adaption toward compounds and polymers with useful electronic properties.¹³

The cyclization represents a rare instance where C-C bond formation occurs without the need for functionality directly participating in condensation or other reactive chemistry. Apparently, after deprotonation, the unsaturation of the 3-carbon substituent on sulfur is sufficient to activate ring closure.

2.2. Mechanism and Computations

Theoretical calculations have been conducted to help rationalize the base induced 5-endo cyclization of benzyl 1-alkynyl sulfides, which led us to the mechanistic proposal in Scheme 1, slightly modified from that reported in the original communication of 2000.⁸ Model system 1a was used to mimic the core of benzyl alkynyl sulfides bearing substituents on the aryl ring. Because it was impractical to compute the reaction with the potassium t-butoxide base, the potential energy surface was calculated for the formation of 2,3-dihydrothiophene 2a in a reaction of 1a with potassium methoxide. Geometries were optimized with CAM-B3LYP/6-311+G(d,p)^14,15,16 in acetonitrile with the CPCM solvent model.¹⁷

Scheme 1.

The calculated structures are shown in Figure 1 where K⁺-π interactions are found for all structures. It is interesting to note that π-cation interactions are influenced less by inductive effects and more by through-space effects between the metal ion and substituents on the aromatic rings,¹⁸ and that the nitro substituent causes the ring to have a very weak π-cation interaction. Because of the complexity of the PES for the parent system 1a, a computational examination of substituent effects was beyond the scope of our study.

Figure 1.

Optimized CPMC-CAM-B3LYP/6-311+G(d,p) geometries for the KOMe-induced cyclization of 1a. Calculations were carried out in acetonitrile. K⁺, KOMe, and MeOH molecules were modeled explicitly. Bolded numbers aligned near the structures are bond distances in Å. Unbolded numbers on some of the structures are the atomic numbers referred to in Table 2.

The energetic features of the reaction are shown in Figure 2. From Figure 2A it is clear that allenyl species 6 plays a key role in the cyclization process to 2,3-dihydrothiophene 2a because it is stabilized compared to 8.

Figure 2.

A–C. CPCM-CAM-B3LYP/6-311+G(d,p) optimized potential energy surface in kcal/mol including thermal corrections for enthalpy (273.15 K). KOMe, K⁺, and MeOH molecules were modeled explicitly. Transition states were confirmed by intrinsic reaction coordinate (IRC) calculations.

The formation of 4 from 1a is a “dead end” and did not convert to cyclic products. Allene 6 is formed in a two-step process from 1a via intermediate 5. A transition state for the loss of a benzylic proton from 6 has an activation barrier of 7.9 kcal/mol (Figure 2B). Upon formation of deprotonated allene 9, it can undergo a unimolecular 5-endo-trig cyclization yielding anion 10, followed by protonation to form 2a. While the thia-Wittig rearrangment has been elucidated yielding 11 (Figure 2C), the experimental data suggest a rapid protonation of 10 and the formation of 2a. An alternative mechanism involves the conversion of deprotonated alkyne 12 via a 5-endo-dig cyclization to give 13 followed by protonation to form 14; however, the path to 12 is higher in energy.

Control experiments were performed in order to provide further understanding of the reaction mechanism. When the reaction was performed in CD₃CN, the products possessed essentially full deuteration at the non-aryl carbons, a result consistent with significant solvent intervention. Indeed, deuterium exchange experiments showed that methyl hydrogens of thioethers 1a, b, i, j each exchanged with half-lives of ca. 25 s at −10 °C, whereas benzyl hydrogen exchange was faster, completing in <25 s at the same temperature. The onset of product was scaled to be substantially longer at the same temperature. Related experiments reaffirmed that the preferred tautomeric state of the 3-carbon unit was the 1-propynyl form as propargyl or allenyl tautomers were never observed by ¹H NMR of the cyclization mixture contents. Such an observation is fully consistent with past literature that indicates the conjugated form is the more thermodynamically stable.¹⁹ Similarly, the computed protonation-deprotonation equilibria which involve 1a, 4–8 show relatively low activation energies of 0.4–8.2 kcal/mol and provide an explanation of how proton or deuterium can be incorporated in all C-H sites except on the phenyl ring.

In the condensed phase, our computations did not find a transition state(s) for the isomerization of 2a to 14. Additional control experiments on 2b in CD₃CN, revealed minimal incorporation of D into the material. The 2,3-dihydro isomer (2b) is not amenable to migration of the double bond because its exchange is quite slow. We did not probe the equilibrium between 2b and 14b due to this slow exchange. The rate of H/D exchange of the starting material is substantially more rapid. It can be noted that re-exposure of 14u (2,5-dihydro isomer of 2u) to the reaction conditions causes the 2u/14u isomer ratio to be reestablished. However, 2u does not exchange when re-exposed to the reaction conditions in CD₃CN. Attempts to prepare 14a in order to study its exchange and isomerization behavior were not successful.

The reaction is most certainly a base mediated cyclization onto the terminus of the three carbon unit. The experimental exchange and computational data suggests that the propynyl/allenyl/propargyl equilibrium is dynamic, with the propynyl as the most populated entity (Figure 2A). From Figure 2, it is evident that formation of allenyl species is favored to the propargyl species and accounts for the path to 2,3-dihydrothiophene product in acetonitrile. 2,3-Dihydrothiophene 2a and 2,5-dihydrothiophene 14 are essentially isoenergetic. The relative energies of these two dihydrothiophene products were calculated to be within 2.8 kcal/mol of each other (Table S1). A change in the solvent or benzyl alkynyl sulfide structure may shift the reaction to propargyl species and the path to 2,5-dihydrothiophene product. The more rapid exchange at the benzylic site suggests that benzylic anions are available to attack the terminus of the 3-carbon unit when unsaturation is available (see Figure 2C).

While there is ongoing interest in assessing endo vs exo cyclization preferences for single species,²⁰ we were not able to locate literature analyses of competitive endo cyclizations of equilibrating species. Given our findings, the chemistry at hand does not present a true competition, nevertheless our determination of transition state energies and parameters permits a comparison of two different but closely related entities. The simplicity of the system may serve as a model for other fundamental cyclizations affording five-membered rings.

Baldwin’s rules suggest the 5-endo-dig cyclization should be allowed, and the 5-endo-trig should not.²¹ However, the 5-endotrig example in the current paper is allene-based with a geometry very close to the alkyne tautomer and was not specifically addressed by Baldwin.²² As such, the cyclization tendencies of this comparison are difficult to distinguish without the assistance of computational chemistry.

The transitions states TS9/10 and TS12/13 differ only by a few kcal/mol. Furthermore, many of the calculated parameters are quite similar in the two transition states. For instance, the degrees of rehybridization of the benzylic carbon in the transitions states, as measured by changing dihedral angles, are essentially indistinguishable. However, the transition state differences worth noting relate to C-C bond formation, C(3)-S bond lengthening and the bending of the three carbon unit (Table 2).

Table 2.

Selected computation data for cyclizations.^a

	9		12
Original bond lengths of key atoms	C(2)-C(1)	1.30	C(2)-C(1)	1.20
	C(3)-C(2)	1.30	C(3)-C(2)	1.45
	S(4)-C(3)	1.80	S(4)-C(3)	1.86
Original indication of planarity of anion	C(7)-C(6)-C(5)-H(17)	−164.7	C(7)-C(6)-C(5)-H(18)	−171.3
	C(8)-C(6)-C(5)-H(17)	20.00	C(8)-C(6)-C(5)-H(18)	14.3
3-C bond angle	C(1)-C(2)-C(3)	178.6	C(1)-C(2)-C(3)	179.6
	TS9/10		TS12/13
Bond lengths of key bonds	C(2)-C(1)	1.36	C(2)-C(1)	1.24
	C(3)-C(2)	1.29	C(3)-C(2)	1.42
	S(4)-C(3)	1.94	S(4)-C(3)	2.04
Bond forming distance	C(5)-C(1)	2.37	C(5)-C(1)	2.33
3-C bond angle	C(1)-C(2)-C(3)	133.8	C(1)-C(2)-C(3)	137.0
Rehybridization dihedral angles	C(7)-C(6)-C(5)-H(17)	173.5	C(7)-C(6)-C(5)-H(18)	173.0
	C(8)-C(6)-C(5)-H(17)	−8.33	C(8)-C(6)-C(5)-H(18)	−8.2
	10		13
Bond lengths of key atoms	C(1)-C(2)	1.52	C(2)-C(1)	1.34
	C(2)-C(3)	1.33	C(3)-C(2)	1.49
	C(3)-S(4)	1.86	S(4)-C(3)	1.90
3-C bond angle	C(3)-C(2)-C(1)	109.5	C(3)-C(2)-C(1)	112.4

^aThe numbering scheme is shown in Figure 1. Bond distances in Å. Bond angles and dihedral angles in degrees.

Transition state TS9/10 exhibits C-C bond forming at 2.37 Å, C(3)-S bond lengthening of 0.13 Å and a bend of the allene unit to 134°. As a comparison, TS12/13 has closer C-C contacts at 2.33 Å, extra lengthening of C(3)-S (0.21 Å) and a lesser degree of bending at the sp hybridized carbon (137°). Clearly, TS12/13 calls upon and benefits from the extra lengthening of the C(3)-S bond and there is less inclination to bend at the allenyl/propynyl central carbon. Both of these features permit advanced C-C bond formation in the transition state. The TS9/10 transition state is achieved with more bending at the allenyl carbon but with less developed C-C bond formation and does not require as much C(3)-S bond lengthening.

The data suggest the allene is more receptive to cyclization than the propynyl unit, as it demonstrates a greater propensity to bend during the cyclization. It is possible that such behaviour would also come into play with other 5-endo-dig/trig cyclizations such as with systems absent of sulfur or any other atom that could accommodate electron density.

3. Conclusions

A simple base-induced transition metal free 5-endo cyclization of benzyl 1-alkynyl sulfides (1) proceeds without the need for activating of electron withdrawing substituents directly attached to skeletal carbons. The 2,3-dihydrothiophene products (2) can be readily forwarded to 2-aryl thiophenes. Computation chemistry was performed to assist in the understanding of mechanism of cyclization and establish which allenyl/propargyl tautomer is likely involved in the cyclization.

It is significant that the allenyl species 6, formed in a stepwise path via 5, is more stable than the propargyl species 8. The weaker benzylic proton affinity of 6 than 8 favors the base induced reaction of 6. From allenyl species 6, 2,3-dihydrothiophene 2a can be formed in three steps, including base 9, which undergoes a 5-endo-trig cyclization to 10.

4. Experimental

4.1. General

Melting points were determined using a MEL-TEMP melting point apparatus and are uncorrected. Infrared (IR) spectra were obtained on a Bomem FTIR spectrometer either neat or in a solution cell (CH₂Cl₂ or CDCl₃). NMR spectra for ¹H and ¹³C NMR were recorded on a Bruker spectrometer at 400 and 100.6 MHz in CDCl₃ solution and are reported in parts per million δ (ppm) relative to tetramethylsilane internal standard or CDCl₃ at 7.26 ppm. Elemental analyses were performed by MHW labs of Phoenix, AZ. Mass spectrometry was performed at the McMaster Regional Centre for Mass Spectrometry, McMaster University or the WATSPEC Mass Spectrometry Facility at the University of Waterloo. Diethyl ether and tetrahydrofuran (THF) were freshly distilled from sodium and benzophenone. Methylene chloride was freshly distilled from calcium hydride. Acetonitrile was distilled from calcium hydride and stored over 4Å molecular sieves under an N₂ atmosphere. Potassium t-butoxide was stored in a vial in a desiccator with anhydrous CaSO₄. All air and water sensitive reagents were transferred using oven-dried nitrogen-purged glass syringes. Flash chromatography was performed on new mesh Type 60 Å silica gel. Analytical thin-layer chromatography (TLC) was performed using 0.25 mm Merck Kieselgel 60 F254 glass-backed plates.

4.2. Computational methods

Density Functional Theory (DFT) calculations were conducted using the Gaussian 09¹⁵ suite of programs. The CAM-B3LYP method corrected for the long range deficiencies of B3LYP and provided results close to coupled cluster calculations.²³ Condensed phase calculations for acetonitrile were carried out with the conductor-like polarizable continuum model (CPCM) of Cossi and coworkers¹⁷ with the smoothing formalism that Karplus and York developed.^14e The solute molecular cavity was specified using the Bondi radii values.²⁴ The computed values include thermal (273.15 K) corrections for enthalpy. Transition states were confirmed by examining the negative eigenvalue of the hessian matrix and by intrinsic reaction coordinate (IRC) calculations. GaussView 5 was used for the visualization of the molecules and the vibrational modes.¹⁶

There are some shortcomings with the B3LYP functional.²⁵ For example, medium and long-range electron correlation errors are common.²⁶ The CAM-B3LYP functional was selected because of its good performance in calculations of electronic polarizabilities, as well as long-range exchange interactions by a Coulomb attenuating method, and medium-range interactions with an error fitting function.²⁷

Table 3 shows that the CAM-B3LYP calculation predicts greater stability of propyne vs allene, which is opposite to that found by experimental, and M05-2X and CCSD(T) methods. The relative energetics of MP4,^19b CCSD(T), and CAM-B3LYP calculations are quite similar to each other for methyl prop-1-yn-1-yl sulfane and methyl propa-1,2-dien-1-yl sulfane. However, our CAM-B3LYP calculations are not expected to have greater accuracy than ~4 kcal/mol. The average errors of B3LYP in thermochemistry calculations was ~3.6 kcal/mol (from a database of 177 reactions).²⁸

Table 3.

Relative energies of propyne and allene, and of methyl prop-1-yn-1-yl sulfane and methyl propa-1,2-dien-1-yl sulfane.

Method	E (kcal/mol)	reference
Experimentall	−1.4	29
CCSD(T)/cc-pVQZ/MP2/cc-pVTZ	−1.4	30
M05-2X/6-311+G(2df,2p)	−1.2	31
CAM-B3LYP/6-311+G(d,p)	0.8	this work
Method	E (kcal/mol)	reference
MP4/6-31+G(d)//RHF/6-31+G(d)	1.3	19b
IEFPCM-MP4/6-31+G(d)//PCM-RHF/6-31+G(d)	1.8	19b
CAM-B3LYP/6-311+G(d,p)	3.4	this work
CPCM-CAM-B3LYP/6-311+G(d,p)	2.6	this work
CCSD(T)/cc-pVQZ/MP2/cc-pVTZ	1.3	this work
CPCM-CCSD(T)/cc-pVQZ/CPCM-MP2/cc-pVTZ	0.6	this work

4.3. General procedure for the cyclization of benzyl propynyl sulfides

In a flame-dried rbf is placed the benzyl propynyl sulfide (1 eq.) in dry CH₃CN (1 mL per 5 mg of substrate). In a second flask is placed KOtBu (2.0 eq.) in dry CH₃CN (1 mL per 5 mg of substrate). The solution of the substrate is added to the KOtBu solution via syringe and the reaction is stirred at r.t. or reflux for 24h. Upon completion of the reaction, de-ionized water (DI) H₂O is added and the layers separated. The aqueous layer is extracted with EtOAc (3x). The organics are combined, washed with DI H₂O (1x), sat’d. aq. NaCl (1x), dried over MgSO₄ and concentrated. See Table 1 for additional detail.

4.3.1. 2-Phenyl-2,3-dihydrothiophene (2a)

The reaction of benzyl 1-propynyl sulfide 1a (337 mg, 2.08 mmol) with KOtBu (467 mg, 4.16 mmol) in refluxing acetonitrile yielded 2,3-dihydrothiophene 2a (57.8 mg; 17%) and recovered starting material (132 mg) after flash chromatography. The yield based on recovered starting material was 28%. Spectral data was obtained as a mixture of the two compounds. ¹H NMR (400 MHz, CDCl₃), δ: 7.41 (d, J = 7.4 Hz, 1H, Ar H), 7.30 – 7.33 (m, 2H, Ar H), 7.23 – 7.26 (m, 2H, Ar H), 6.23 (dt, J = 6.0 & 2.4 Hz, 1H, vinyl H), 5.59 (dt, J = 6.0 & 2.4 Hz, 1H, vinyl H), 4.91 (dd, J = 9.6 & 7.3 Hz, 1H, CH), 3.20 (ddt, J = 16.5, 9.6 & 2.4 Hz, 1H, CH₂), 2.93 (ddt, J = 16.5, 7.3 & 2.4 Hz, 1H, CH₂). Partial ¹³C NMR (100.6 MHz, CDCl₃), δ: 128.6, 127.4, 127.0, 125.6, 120.5, 52.7, 43.9.

4.3.2. 2-(2-Iodophenyl)-2,3-dihydrothiophene (2b)

The reaction of 2-iodobenzyl propynyl sulfide (1b) (194 mg, 0.674 mmol) with KOtBu (180 mg, 1.35 mmol) yielded 2,3-dihydrothiophene 2b (180 mg; 75%) as a yellow liquid after flash chromatography. ¹H NMR (400 MHz, CDCl₃), δ: 7.84 (dd, J = 7.7 & 1.1 Hz, 1H, Ar H), 7.61 (dd, J = 7.7 & 1.6 Hz, 1H, Ar H), 7.33 (dt, J = 7.7 & 1.1 Hz, 1H Ar H), 6.94 (dt, J = 7.7 & 1.6 Hz, 1H, Ar H), 6.25 (ddd, J = 6.0, 2.6 & 1.7 Hz, 1H, vinyl H), 5.63 (dt, J = 6.0 & 2.8 Hz, 1H, vinyl H), 5.13 (dd, J = 9.7 & 5.0 Hz, 1H, CH), 3.27 (ddt, J = 16.8, 9.7 & 2.8 Hz, 1H CH₂), 2.83 (dddd, J = 16.8, 5.0, 2.8 & 1.7 Hz, 1H, CH₂). ¹³C NMR (100.6 MHz, CDCl₃), δ: 145.6, 139.4, 128.9, 128.7, 127.5, 125.4, 120.4, 99.9, 56.0, 42.9. IR (neat, cm⁻¹) 3060, 2937, 2894, 2844, 1583, 1563, 1463, 1436, 1012. EIMS, m/z (%): 288 (7, M⁺), 161 (37), 128 (100), 127 (23), 116 (17), 115 (39), 89 (19), 85 (18), 77 (32), 63 (25), 62 (15), 51 (32), 50 (28), 45 (31). HREIMS: Calc’d for C₁₀H₉SI: 287.9470. Found: 287.9457.

4.3.3. 2-(2-Bromophenyl)-2,3-dihydrothiophene (2c)

The reaction of 2-bromobenzyl propynyl sulfide (1c) (209 mg, 0.867 mmol) with KOtBu (195 mg, 1.73 mmol) in acetonitrile yielded 2,3-dihyrothiophene 2c (154 mg; 74%) as a yellow liquid after flash chromatography. ¹H NMR (400 MHz, CDCl₃), δ: 7.62 (dd, J = 7.7 & 1.6 Hz, 1H, Ar H), 7.55 (dd, J = 7.7 & 1.2 Hz, 1H, Ar H), 7.29 (dt, J = 7.7 & 1.2 Hz, 1H, Ar H), 7.11 (dt, J = 7.7 & 1.6 Hz, 1H, Ar H), 6.24 (ddd, J = 6.0, 2.6 & 1.7 Hz, 1H, vinyl H), 5.61 (dt, J = 6.0 & 2.9 Hz, vinyl H), 5.27 (dd, J = 9.7 & 4.9 Hz, 1H, CH), 3.27 (ddt, J = 16.8, 9.7 & 2.6 Hz, 1H, CH₂), 2.86 (dddd, J = 16.8, 4.9, 2.9 & 1.7 Hz, 1H, CH₂). ¹³C NMR (100.6 MHz, CDCl₃), δ: 142.5, 132.7, 128.7, 128.1, 127.9, 125.4, 123.3, 120.4, 50.8, 42.3. IR (neat, cm⁻¹) 3062, 2938, 2896, 2842, 1588, 1567, 1467, 1440, 1265, 1025. EIMS, m/z (%): 242 (20, M⁺ for ⁸¹Br), 240 (21, M⁺ for ⁷⁹Br), 161 (37), 128 (100), 116 (18), 115 (24), 84 (22), 51 (15), 49 (23), 47 (16), 45 (29). Analysis: Calc’d for C₁₀H₉BrS: C, 49.81; H, 3.76. Found: C, 49.79; H, 3.88.

4.3.4. 2-(2-Chlorophenyl)-2,3-dihydrothiophene (2d)

The reaction of 2-chlorobenzyl propynyl sulfide (1d) (231 mg, 1.18 mmol) with KOtBu (264 mg, 2.35 mmol) in acetonitrile yielded 2,3-dihydrothiophene 2d (171 mg; 74%) as a yellow liquid after flash chromatography. ¹H NMR (400 MHz, CDCl₃), δ: 7.62 (dd, 7.6 & 1.7 Hz, ¹H, Ar H), 7.36 (dd, J = 7.6 & 1.4 Hz, 1H, Ar H), 7.25 (dt, 7.6 & 1.4 Hz, 1H, Ar H), 7.19 (dt, J = 7.6 & 1.7 Hz, 1H, Ar H), 6.24 (ddd, J = 6.0, 2.6 & 1.8 Hz, 1H, vinyl H), 5.60 (dt, J = 6.0 & 3.0 Hz, 1H, vinyl H), 5.31 (dd, J = 9.7 & 5.1 Hz, 1H, CH), 3.26 (ddt, 16.7, 9.7 & 2.6 Hz, 1H, CH₂), 2.87 (dddd, 16.7, 5.1, 3.0 & 1.8 Hz, 1H, CH₂). ¹³C NMR (100.6 MHz, CDCl₃), δ: 140.8, 132.7, 129.4, 128.4, 127.9, 127.2, 125.4, 120.4, 48.1, 42.2. IR (neat, cm⁻¹) 3070, 2939, 2896, 2842, 1472, 1444, 1051, 1037. EIMS, m/z (%): 196 (7, M⁺ for ³⁷Cl), 194 (7, M⁺ for ³⁵Cl), 86 (31), 84 (46), 58 (22), 51 (20), 49 (72), 47 (15), 43 (100), 42 (15). HREIMS: Calc’d for C₁₀H₉ClS: 196.0113. Found: 196.0101.

4.3.5. 2-(2-Phenylphenyl)-2,3-dihydrothiophene (2f)

The reaction of 2-phenylbenzyl propynyl sulfide (1f) (157 mg, 0.659 mmol) with KOtBu (148 mg, 1.32 mmol) in refluxing acetonitrile yielded a mixture of 2,3-dihydrothiophene 2f (38.6 mg; 25%) and recovered starting material (63.2 mg) after flash chromatography. The yield based on recovered starting material was 41%. Spectral data obtained as a mixture of dihydrothiophene 2f and benzyl propynyl sulfide 1f. ¹H NMR (400 MHz, CDCl₃), δ: 7.51 - 7.17 (m, 9H, Ar H’s), 6.18 (dt, J = 4.6 & 2.0 Hz, 1H, vinyl H), 5.51 (dt, J = 4.6 & 3.1 Hz, vinyl H), 4.97 (dd, J = 9.5 & 7.3 Hz, 1H, CH), 3.06 - 2.93 (m, 2H, CH₂).

4.3.6. 2-(2-Fluorophenyl)-2,3-dihydrothiophene (2g)

The reaction of 2-fluorobenzyl propynyl sulfide (1g) (204 mg, 1.13 mmol) with KOtBu (255 mg, 2.27 mmol) in refluxing acetonitrile yielded 2,3-dihydrothiophene 2g (92 mg; 45%) as a yellow liquid after flash chromatography. ¹H NMR (400 MHz, CDCl₃), δ: 7.56 (dt, J = 7.7, 1.7 Hz, ¹H), 7.26 – 7.20 (m, 1H), 7.12 (t, J = 7.7 Hz, 1H), 7.02 (ddd, J = 10.3, 8.2, 1.1 Hz, 1H), 6.42 (ddd (app. dt), J = 6.1, 2.3, 2.3 Hz, 1H), 5.60 (dt, J = 6.1, 2.8 Hz, 1H), 5.20 (dd, J = 9.7, 6.1 Hz), 3.22 (dddd (apparent ddt), J = 16.6, 9.7, 2.6, 1H), 2.90 (dddd (apparent ddt), J = 16.6, 6.1, 2.6, 1H). ¹³C NMR (100.6MHz, CDCl₃), δ: 159.6 (d, J_13C-19F = 246.3), 130.4 (d, J_13C-19F= 13.5 Hz), 128.7 (d, J_13C-19F= 8.2 Hz), 128.2 (d, J_13C-19F= 3.3 Hz), 125.3, 124.3 (d, J_13C-19F= 3.3 Hz), 120.4, 115.2 (d, J_13C-19F= 22.1 Hz), 44.2 (d, J_13C-19F= 2.8 Hz), 42.5. IR (CDCl₃, cm⁻¹): 3066, 3044, 2932, 2892, 2840, 1717, 1614, 1585, 1488, 1456, 1278, 1264, 1230, 1173, 1094, 1035, 1006, 832, 805. CIMS, m/z (%): 181.0 (24, (M+H)⁺), 180.0 (100, M⁺), 179.0 (15, (M−H)⁺), 147.1 (40), 146.1 (14), 49.0 (22). Anal. Calc’d. for C₁₀H₉SF, C: 66.64%, H: 5.03%; found, C: 66.41%, H: 5.13%.

4.3.7. 2-(2-Cyanophenyl)-2,3-dihydrothiophene (2h)

The reaction of 2-cyanobenzyl propynyl sulfide (1h) (239 mg, 1.27 mmol) with KOtBu (286 mg, 2.55 mmol) in acetonitrile yielded 2,3-dihydrothiophene 2h^7a (153 mg, 64%) as a white solid (m.p. 83 – 84.5°C) after flash chromatography. ¹H NMR (400 MHz, CDCl₃), δ: 7.75 (d, J = 8.0Hz, 1H), 7.63-7.54 (m, 2H), 7.34 (t, J = 7.6 Hz, 1H), 6.24 (ddd apparent dt), J = 6.0, 2.1 Hz, 1H), 5.58 (dt, J = 6.0, 2.7 Hz, 1H), 5.26 (dd, J = 9.9, 5.5 Hz, 1H), 3.34 (ddt, J = 16.8, 9.9, 2.5 Hz, 1H), 2.87 (dddd (apparent ddt), J = 16.8, 5.5, 2.6 Hz, 1H). ¹³C NMR (100.6 MHz, CDCl₃), δ: 147.5, 133.4, 132.7, 127.7, 127.6, 125.4, 120.1, 117.5, 111.0, 49.2, 43.5. IR (CH₂Cl₂, cm⁻¹): 3018, 2843, 2226, 1599, 1482, 1449, 1212, 1166, 1041, 1003. CIMS, m/z (%): 188.1 (27, (M+H)⁺), 187.0 (56, M⁺), 186.0 (100, (M−H)⁺), 154.1 (21). Anal. Calc’d. for C₁₁H₉SN, C: 70.55%, H: 4.84%; found, C: 70.53%, H: 5.04%.

4.3.8. 2-(3-Iodophenyl)-2,3-dihydrothiophene (2i)

The reaction of 3-iodobenzyl propynyl sulfide (1i) (591 mg, 2.05 mmol) with KOtBu (460 mg, 4.10 mmol) in acetonitrile yielded 2,3-dihydrothiophene 2i (402 mg, 68%) as a yellow oil after flash chromatography. ¹H NMR (400 MHz, CDCl₃), δ: 7.92 (s, 1H), 7.75 (d, J = 7.9 Hz, 1H), 7.53 (d, J = 7.9 Hz, 1H), 7.22 (t, J = 7.9 Hz, 1H), 6.40 (ddd (apparent dt), J = 6.1, 2.2 Hz, 1H), 5.74 (dt, J = 6.1, 2.7 Hz, 1H), 4.96 (dd, J = 9.7, 6.7 Hz, 1H), 3.37 (ddt, J = 16.6, 9.7, 2.2 Hz, 1H), 3.05 (dddd (apparent ddt), J = 16.6, 6.7, 2.7 Hz, 1H). ¹³C NMR (100.6MHz, CDCl₃), δ: 145.9, 136.4, 135.9, 130.3, 126.3, 125.5, 120.3, 94.4, 51.7, 43.8. IR (neat, cm⁻¹): 3052, 2925, 2836, 1714, 1587, 1563, 1471, 1421, 1263, 1193, 1065, 994, 882, 781. CIMS, m/z (%): 305 (70, (M+NH₃)⁺), 289 (14, (M+H)⁺), 161 (6), 128 (7). Anal. Calc’d. for C₁₀H₉SI, C: 41.68%, H: 3.15%; found, C: 41.48%, H: 3.25%.

4.3.9. 2-(4-Iodophenyl)-2,3-dihydrothiophene (2j)

The reaction of 4-iodobenzyl propynyl sulfide (1j) (556 mg, 1.93 mmol) with KOtBu (433 mg, 3.86 mmol) in acetonitrile yielded 2,3-dihydrothiophene 2j (250 mg, 45%) as a yellow oil after flash chromatography. ¹H NMR (400 MHz, CDCl₃), δ: 7.80 (d, J = 8.4 Hz, 2H), 7.32 (d, J = 8.4 Hz, 2H), 6.40 (ddd (apparent dt), J = 6.1, 2.0 Hz, 1H), 5.74 (dt, J = 6.1, 2.7 Hz, 1H), 4.99 (dd, J = 9.7, 6.7 Hz, 1H), 3.36 (ddt, J = 16.6, 9.7, 2.4 Hz, 1H), 3.03 (dddd (apparent ddt), J = 16.6, 6.7, 2.4 Hz, 1H). ¹³C NMR (100.6 MHz, CDCl₃), δ: 143.3, 137.6, 128.9, 125.5, 120.3, 92.6, 51.9, 43.8. IR (neat, cm⁻¹): 3054, 3019, 2927, 2854, 1900, 1713, 1584, 1564, 1484, 1434, 1400, 1277, 1259, 1102, 1005, 943, 911, 857, 818, 780. EIMS, m/z (%): 288 (78, M⁺), 161 (8), 128 (100), 115 (30). HREIMS Calc’d for C₁₀H₉SI: 287.9466. Found: 287.9470.

4.3.10. 3-(Trifluoromethyl)phenyl-2,3-dihydrothiophene (2k)

The reaction of 3-(trifluoromethyl)benzyl propynyl sulfide (1k) (218 mg, 0.95 mmol) with KOtBu (213 mg, 1.89 mmol) in refluxing acetonitrile yielded 2,3-dihydrothiophene 2k (122 mg, 59%) as a yellow oil after flash chromatography. ¹H NMR (400 MHz, CDCl₃), δ: 7.65 (s, 1H), 7.59 (d, J = 7.7 Hz, 1H), 7.51 (d, J = 7.7 Hz, 1H), 7.43 (t, J = 7.7 Hz, 1H), 6.24 (ddd (apparent dt), J = 6.1, 2.2 Hz, 1H), 5.59 (dt, J = 6.1, 2.8 Hz, 1H), 4.91 (dd, J = 9.7, 6.5 Hz, 1H), 3.24 (ddt, J = 16.6, 9.7, 2.6 Hz, 1H), 2.91 (dddd, J = 16.6, 6.5, 2.8, 2.2 Hz, 1H). ¹³C NMR (100.6 MHz, CDCl₃), δ: 144.6, 130.8(q, J_13C-19F= 32.3 Hz), 130.4, 129.1, 125.5, 124.2, 124.0 (q, J₁₃C19F = 272.1 Hz), 123.8, 120.3, 51.8, 43.9. IR (neat, cm⁻¹): 3066, 2930, 1716, 1613, 1596, 1492, 1450, 1329, 1261, 1166, 1125, 1098, 1073, 1002, 902, 804, 739, 702. CIMS m/z (%): 231 (10, (M+H)⁺), 230 (59, M⁺), 197 (12), 177 (16), 86 (24), 84 (38), 51 (35), 49 (100), 47 (17), 30 (22). HRCIMS Calc’d. for C₁₁H₉F₃S: 230.0377. Found: 230.0372.

4.3.11. 2-(Phenylthio)phenyl-2,3-dihydrothiophene (2l)

The reaction of 2-(phenylthio)benzyl propynyl sulfide (1l) (210 mg, 0.77 mmol) with KOtBu (172 mg, 1.53 mmol) in refluxing acetonitrile yielded 2,3-dihydrothiophene 2l (137 mg, 66%) as a yellow oil after flash chromatography. ¹H NMR (400 MHz, CDCl₃), δ: 7.72 (dd, J = 7.9, 1Hz, 1H), 7.38-7.14 (m, 8H), 6.21 (ddd, J = 6.1, 2.2, 2.0 Hz, 1H), 5.56 (dt, J = 6.1, 2.7 Hz, 1H), 5.50 (dd, J = 9.9, 5.6 Hz, 1H), 3.13 (ddt, J = 16.8, 9.9, 2.7 Hz, 1H), 2.82 (dddd, J = 16.8, 5.0, 2.7, 2.0 Hz, 1H). ¹³C NMR (100.6 MHz, CDCl₃), δ: 145.7, 136.5, 134.0, 132.1, 129.4, 129.1, 128.9, 128.0, 127.7, 126.4, 125.5, 120.3, 48.6, 43.0. IR (CDCl₃, cm⁻¹): 3057, 3016, 2926, 2839, 1717, 1581, 1476, 1466, 1439, 1328, 1301, 1277, 1194, 1158, 1083, 1068, 1057, 1038, 1024, 1000, 738. CIMS, m/z (%): 271 (97, (M+H)⁺), 270 (100, M⁺), 242 (27), 223 (20), 215 (17), 214 (25), 197 (29), 193 (75), 161 (48), 160 (30), 147 (17), 128 (33), 115 (16). Anal. Calc’d. for C₁₆H₁₄S₂, C: 71.07%, H: 5.22%; found, C: 70.92%, H: 5.30%.

4.3.12. 2-(Phenylsulfinyl)phenyl-2,3-dihydrothiophene (2m)

The reaction of 2-(phenylsulfinyl)benzyl propynyl sulfide (1m) (119 mg, 0.41 mmol) with KOtBu (93.5 mg, 0.83 mmol) in refluxing acetonitrile yielded 2,3-dihydrothiophene 2m (528 mg, 45%) as a white solid and a 1:1 mixture of diastereomers after flash chromatography on silica gel (20–40% hexanes eluent). ¹H NMR (400 MHz, CDCl₃, mixture of isomers), δ: 7.95 – 7.93 (m, 1H), 7.86 – 7.84 (m, 1H), 7.73 – 7.71 (m, 2H), 7.60 - 7.56 (m, 2H), 7.50 – 7.45 (m, 5H), 6.17 (ddt, J = 8.4, 5.9, 2.2 Hz. 1H), 5.57 (dt, J = 5.9, 2.8 Hz, 0.5H), 5.42 (ddt (apparent dt), J = 8.4, 2.3 Hz, 0.5H), 5.31 – 5.28 (m, 0.5H), 3.25 (ddt, J = 16.8, 10.0, 2.6 Hz, 0.5 H), 2.94 (dddd, J = 16.8, 5.7, 3.2, 2.5 Hz, 0.5H), 2.80 (ddt, J = 16.8, 10.0, 2.6 Hz, 0.5H), 2.51 (dddd, J = 16.8, 5.7, 3.2, 2.5, 0.5H). ¹³C NMR (100.6 MHz, CDCl₃, mixture of isomers), δ: 144.9, 144.6, 142.7, 142.5, 141.8, 132.1, 132.0, 131.3, 131.2, 129.4, 129.0, 128.7, 128.6, 128.4, 127.7, 126.0, 125.5, 125.3, 125.2, 125.0, 120.4, 119.6, 46.3, 46.0, 44.0, 43.7. IR (CDCl₃, cm⁻¹): 3057, 2927, 2839, 1582, 1472, 1442, 1328, 1306, 1279, 1260, 1191, 1159, 1122, 1083, 1035, 998, 960, 918, 850. CIMS, m/z (%): 288.1 (3, (M+H)⁺), 287 (19, M⁺), 242 (22), 235 (11), 233 (19), 217 (12), 200 (24), 199 (21), 197 (45), 194 (13), 193 (100), 192 (23), 191 (57), 184 (12), 162 (10), 161 (68), 160 (57), 159 (18), 147 (40), 134 (15), 128 (65), 116 (14), 115 (39). HRCIMS: Calc’d. for C₁₆H₁₅S₂O: 287.0564. Found: 287.0563.

4.3.13. 2-(Phenylsulfonyl)phenyl-2,3-dihydrothiophene (2n)

The reaction of 2-(phenylsulfonyl)benzyl propynyl sulfide (1n) (207 mg, 0.69 mmol) with KOtBu (154 mg, 1.37 mmol) in refluxing acetonitrile yielded 2,3-dihydrothiophene 2n (141 mg, 68%) as a yellow solid after flash chromatography on silica gel (m.p. 109 – 113 °C). ¹H NMR (400 MHz, CDCl₃), δ: 8.17 (dd, J = 8.0, 1.2 Hz, 1H), 7.87 – 7.82 (m, 3H), 7.62 – 7.51 (m, 4H), 7.44 (dt, J = 8.0, 1.2 Hz, 1H), 6.12 (ddd, J = 6.0, 2.0, 2.0 Hz, 1H), 5.66 (dd, J = 10.3, 5.0 Hz, 1H), 5.46 (ddd (apparent dt), J = 6.0, 2.7 Hz, 1H), 3.09 (ddt, J = 17.1, 10.3, 2.7), 2.69 (dddd, J = 17.1, 5.0, 2.7, 2.0 Hz, 1H). ¹³C NMR (100.6MHz, CDCl₃), δ: 144.7, 141.6, 137.0, 134.5, 133.3, 129.6, 129.3, 128.9, 127.6, 127.4, 125.3, 119.9, 45.7, 44.4. IR (CDCl₃, cm⁻¹): 3072, 2935, 2846, 2686, 1590, 1571, 1470, 1447, 1315, 1156, 1126, 1091, 1058. CIMS m/z (%): 303 (67, (M+H)⁺), 302 (21, M⁺), 238 (32), 237 (19), 233 (11), 214 (16), 192 (17), 191 (100), 166 (16), 165 (11), 161 (19), 160 (61), 129 (12), 128 (41), 125 (16), 116 (15), 115 (37), 91 (25), 78 (17), 77 (25). HRCIMS: Calc’d for C₁₆H₁₅O₂S₂: 303.0513. Found: 303.0530.

4.3.14. 2,5-Dimethoxyphenyl-2,3-dihydrothiophene (2o)

The reaction of 2,5-dimethoxybenzyl propynyl sulfide (1o) (300 mg, 1.35 mmol) with KOtBu (304 mg, 2.71 mmol) in refluxing acetonitrile yielded a mixture of 2,3-dihydrothiophene 2o (81 mg; 27%) and recovered starting material (115 mg) after flash chromatography. The yield based on recovered starting material was 44%. ¹H NMR (400 MHz, CDCl₃), δ: 7.09 (d, J = 2.9 Hz, ¹H, Ar H), 6.73 – 6.80 (m, 2H, Ar H), 6.21 (ddd, J = 6.0, 2.6 & 1.8 Hz, 1H, vinyl H), 5.60 (dt, J = 6.0 & 2.9 Hz, 1H, vinyl H), 5.24 (dd, J = 9.6 & 5.6 Hz, 1H, CH), 3.81 (s, 3H, OCH₃), 3.77 (s, 3H, OCH₃), 3.15 (ddt, J = 16.6, 9.6 & 2.6 Hz, 1H, CH₂), 2.87 (dddd, J = 16.6, 5.6, 2.9 & 1.8 Hz, 1H, CH₂). ¹³C NMR (100.6 MHz, CDCl₃), δ: 148.5, 125.4, 122.7, 120.7, 113.6, 113.2, 112.2, 111.4, 56.1, 55.7, 45.1, 41.7. IR (neat, cm⁻¹) 3004, 2941, 2910, 2837, 1499, 1220, 1048. GC/MS, m/z (%): 222 (100, M⁺), 189 (69), 174 (45), 158 (24), 146 (9), 115 (8), 91 (9), 45 (10).

4.3.15. 3,5-Dimethoxyphenyl-2,3-dihydrothiophene (2p)

The reaction of 3,5-dimethoxy benzyl propynyl sulfide (1p) (270 mg, 1.22 mmol) with KOtBu (275 mg, 2.45 mmol) in refluxing acetonitrile yielded 2,3-dihydrothiophene 2p (113 mg, 42%) as a colourless oil after flash chromatography on silica gel. The yield based on recovered starting material was 54%. ¹H NMR (400 MHz, CDCl₃), δ: 6.57 (d, J = 2.3 Hz, 2H), 6.36 (t, J = 2.3 Hz, 1H), 6.21 (dt, J = 6.1, 2.2 Hz, 1H), 5.57 (dt, J = 6.1, 3.0 Hz, 1H), 4.84 (dd, J = 9.6, 7.3 Hz, 1H), 3.78 (s, 6H), 3.17 (ddt, J = 16.6, 9.6, 2.7 Hz, 1H), 2.92 (dddd, J = 16.6, 7.3, 2.7, 2.2 Hz, 1H). ¹³C NMR (100.6 MHz, CDCl₃), δ: 168.2, 160.8, 145.7, 125.5, 120.6, 105.0(2), 99.2(2), 55.3, 52.9, 43.7. IR (CDCl₃, cm⁻¹): 3073, 3008, 2960, 2940, 2840, 1607, 1596, 1469, 1431, 1350, 1205, 1196, 1157, 1067, 940, 927, 848, 836. CIMS, m/z (%): 223 (40, (M+H)⁺), 222 (51, M⁺), 189 (100), 174 (19), 158 (10). HRCIMS Calc’d. for C₁₂H₁₄O₂S: 222.0715. Found: 222.0715.

4.3.16. 2-(1-Bromonaphth-2-yl)-2,3-dihydrothiophene (2s)

The reaction of 1-bromonaphth-2-yl propynyl sulfide (1s) (209 mg, 0.716 mmol) with KOtBu (161 mg, 1.43 mmol) yielded 2,3-dihydrothiophene 2s (150 mg; 72%) as a yellow liquid after flash chromatography. ¹H NMR (400 MHz, CDCl₃), δ: 8.33 (d, J = 8.5 Hz, 1H, Ar H), 7.79 (m, 3H, Ar H), 7.59 (m, 1H, Ar H), 7.50 (m, 1H, Ar H), 6.30 (ddd, J = 6.0, 2.5 & 1.9 Hz, 1H, vinyl H), 5.70 (dd, J = 10.0 & 5.2 Hz, 1H, CH), 5.65 (dt, J = 6.0 & 2.8 Hz, 1H, vinyl H), 3.38 (ddt, J = 16.9, 10.0 & 2.5 Hz, 1H, CH₂), 2.95 (dddd, J = 16.9, 5.2, 2.8 & 1.9 Hz, 1H, CH₂). ¹³C NMR (100.6 MHz, CDCl₃), δ: 140.7, 133.8, 132.5, 128.3, 128.0, 127.8, 127.5, 126.4, 125.7, 125.3, 122.5, 120.5, 51.6, 43.0. IR (neat, cm⁻¹) 3060, 2933, 2901, 2844, 1502, 1330, 1259, 818. EIMS, m/z (%): 292 (12, M⁺ for ⁸¹Br), 290 (12, M⁺ for ⁷⁹Br), 211 (39), 179 (15), 178 (100), 165 (19). Analysis: Calc’d for C₁₄H₁₁BrS: C, 57.74; H, 3.81. Found: C, 57.90; H, 4.00.

4.3.17. 2,6-Bis (2,3-dihydro-5-thienyl)-2-bromobenzene (2t)

The reaction of 2,6-bis(1-propynylthio)-2-bromobenzene (1t) (201 mg, 0.616 mmol) with KOtBu (277 mg, 2.47 mmol) yielded 2,3-dihydrothiophene 2t (93.4 mg; 47%) as yellow liquid after flash chromatography. ¹H NMR (400 MHz, CDCl₃), δ: 7.51 (d, J = 7.5 Hz, 2H, Ar H), 7.26 (t, J = 7.5 Hz, 1H, Ar H), 6.22 (m, 2H, vinyl H’s), 5.61 (m, 2H, vinyl H’s), 5.34 (dt, J = 9.5 & 3.9 Hz, 2H, CH), 3.26 (m, 2H, CH₂), 2.85 (m, 2H, CH₂). ¹³C NMR (100.6 MHz, CDCl₃), δ: 143.1, 143.0, 128.6, 127.8, 127.8, 127.0, 126.8, 125.5, 125.3, 120.6, 120.4, 51.6, 51.5, 42.3, 42.2. IR (neat, cm⁻¹) 3072, 2933, 2896, 2843, 1415, 1021, 792.

4.3.18. 2-(2-Iodophenyl)-3-propyl-2,3-dihydrothiophenes (2u) and 2-(2-iodophenyl)-3-propyl-2,5-dihydrothiophene (2 u ’)

The reaction of 2-iodobenzyl hexynyl sulfide (1u) (453 mg, 1.37 mmol) with KOtBu (308 mg, 2.75 mmol) in acetonitrile at rt yielded 2,3-dihydrothiophenes 2u (69 mg; 15%) and 2,5-dihydrothiophene 14u (302 mg; 67%) as a yellow liquids after two flash chromatographies. Data for cis-2u: ¹H NMR (400 MHz, CDCl₃), δ: 7.82 (dd, J = 7.7 & 1.2 Hz, 1H, Ar H), 7.74 (dd, J = 7.7 & 1.6 Hz, 1H, Ar H), 7.38 (dt, J = 7.7 & 1.2 Hz, 1H, Ar H), 6.95 (dt, J = 7.7 & 1.6 Hz, 1H, Ar H), 6.29 (dd, J = 6.2 & 1.7 Hz, 1H, vinyl H), 5.68 (dd, J = 6.2 & 2.8 Hz, 1H, vinyl H), 5.35 (d, J = 8.8 Hz, 1H, CH), 3.38 (m, 1H, CH), 1.55 (m, 2H, CH₂), 1.30 - 1.05 (m, 2H, CH₂), 0.78 (t, J = 7.2 Hz, 3H, CH₃). Data for trans-2u: ¹H NMR (400 MHz, CDCl₃), δ: 7.83 (dd, J = 7.8 & 1.1 Hz, 1H, Ar H), 7.54 (dd, J = 7.8 & 1.6 Hz, 1H, Ar H), 7.32 (dt, J = 7.8 & 1.1 Hz, 1H, Ar H), 6.93 (dt, J = 7.8 & 1.6 Hz, 1H, Ar H), 6.19 (dd, J = 6.0 & 1.3 Hz, 1H, vinyl H), 5.65 (dd, J = 6.0 & 2.9 Hz, 1H, vinyl H), 4.73 (d, J = 4.0 Hz, 1H, CH), 3.14 (m, 1H, CH), 1.63 (m, 2H, CH₂), 1.42 (sextet, J = 7.4 Hz, 2H, CH₂), 0.93 (t, J = 7.4 Hz, 3H, CH₃). ¹³C NMR (100.6 MHz, CDCl₃), δ: 146.1, 139.3, 128.8, 127.9, 125.1, 124.4, 100.0, 61.2, 55.9, 36.2, 20.6, 14.2. IR (neat, cm⁻¹) 3047, 2959, 2930, 2873, 1463, 1010, 911. EIMS, m/z (%): 330 (56, M⁺), 287 (100), 160 (56), 128 (19), 115 (34). Data for 14u: ¹H NMR (400 MHz, CDCl₃), δ: 7.80 (dd, J = 7.7 & 1.1 Hz, 1H, Ar H), 7.34 (dt, J = 7.7 & 1.1 Hz, 1H, Ar H), 7.26 (dd, J = 7.7 & 1.8 Hz, 1H, Ar H), 6.92 (ddd, J = 7.7, 7.5 & 1.8 Hz, 1H, Ar H), 5.80 (d, J = 1.0 Hz, 1H, CH), 5.50 (d, J = 5.1 Hz, 1H, vinyl H), 3.89 (m, 1H, CH₂), 3.77 (d (br), J = 14.3, 1H, CH₂), 2.01 - 1.93 (m, 1H, CH₂), 1.88 - 1.81 (m, 1H, CH₂), 1.58 - 1.35 (m, 2H, CH₂), 0.88 (t, J = 7.3 Hz, 3H, CH₃). ¹³C NMR (100.6 MHz, CDCl₃), δ: 146.0, 145.4, 139.2, 129.0, 129.0, 128.7, 124.2, 100.6, 63.8, 37.7, 31.6, 21.2, 13.9. IR (neat, cm⁻¹) 3058, 2962, 2933, 2875, 2850, 1584, 1563, 1463, 1436, 1011, 832, 792. Analysis: Calc’d for C₁₃H₁₅IS: C, 47.28; H, 4.58. Found: C, 47.15; H, 4.46.

4.4. General procedure for the oxidation of 2-aryl-2,3-dihydrothiophenes

To a solution of DDQ (1.6 eq.) in CHCl₃ is added a solution of the dihydrothiophene (1.0 eq.) in CHCl₃. The reaction is stirred at r.t. for 24h. Upon completion of the reaction, the solution is filtered and diluted with CH₂Cl₂ and washed with DI H₂O (4x). The organic solution is then washed with sat’d. aq. NaCl (1x), dried over MgSO₄ and concentrated.

4.4.1. Oxidation of dihydrothiophene 2b

To a solution of 2b (205 mg, 0.71 mmol, 1.0 eq.) in CHCl₃ (15 mL) was added DDQ (258 mg, 1.14 mmol, 1.6 eq.) and the reaction was stirred for 24 h. Workup as indicated and flash chromatography on silica gel (100% hexane eluent) provided thiophene 3b (149 mg, 73%) as a colorless oil. ¹H NMR (400 MHz, CDCl₃), δ: 7.98 (dd, J = 7.9, 0.8 Hz, 1H), 7.45 (dd, J = 7.4, 1.8 Hz, 1H), 7.39 (m, 2H), 7.21 (dd, J = 3.6, 1.1 Hz, 1H), 7.12 (dd, J = 5.1, 3.6 Hz, 1H), 7.02 (dt, J = 7.4, 1.8 Hz, 1H). ¹³C NMR (100.6 MHz, CDCl₃), δ: 144.9, 139.9, 139.4, 131.3, 129.4, 128.1, 127.6, 126.8, 125.9, 99.6. IR (neat, cm⁻¹): 3146, 3119, 2915, 2848, 1723, 1680, 1594, 1501, 1435, 1408, 1375, 1243, 1212, 1151, 1131, 1071, 1011, 937, 886, 809, 739. CIMS, m/z (%): 287 ((M+H)+, 30), 286 (M+, 39), 161 (100), 160 (19). Anal. Calc’d. for C₁₀H₇SI, C: 41.98%, H: 2.47%; found, C: 41.79%, H: 2.60%.

4.4.2. Oxidation of dihydrothiophene 2h

To a solution of 2h (120 mg, 0.64 mmol, 1.0 eq.) in CHCl₃ (15 mL) was added DDQ (233 mg, 1.03 mmol, 1.6 eq.) and the reaction was stirred for 24h. Workup as indicated and flash chromatography on silica gel (5–10% EtOAc/hexane eluent) provided thiophene 3h³² (96.3 mg, 81%) as a colourless oil. ¹H NMR (400 MHz, CDCl₃), δ: 7.72 (dd, J = 8.0, 1.0 Hz, 1H), 7.63 (dd, J = 3.7, 1.0 Hz, 1H), 7.60-7.55 (m, 2H), 7.42 (dd, J = 5.1, 1.0 Hz, 1H), 7.37 (t, J = 6.1, 1.6 Hz, 1H), 7.14 (dd, J = 5.1, 3.7 Hz, 1H). ¹³C NMR (100.6 MHz, CDCl₃), δ: 139.3, 137.4, 134.2, 132.9, 129.6, 128.1, 127.5 (2), 127.2, 118.8, 109.9. IR (neat, cm⁻¹): 3108, 3074, 2224, 1595, 1565, 1528, 1482, 1444, 1354, 1277, 1247, 1213, 1189, 1166, 1107, 1042, 962, 853, 836, 761.