1- Thiabutadiene

Thiabutadienes undergo highly enantioselective hDA reactions in the presence of homochiral bis(oxazoline) and bis(imine) complexes with Cu and Ni (Scheme 37) <99CC1001>. Homochiral camphor-based thiabutadienes show good exo selectivity and give rise to bomene ring-fused dihydrothiopyrans (Scheme 38) <99TL8383>. 

The hetero-Diels-Alder reaction of homochiral camphor-derived thiabutadienes has given, for the first time, optically active bornene ring-fused dihydrothiopyrans with high diastereoselectivity (Scheme 53) <2000H(53)1685>. The exo endo- t2X o varied with the nature of substituent, varying from 91 9 (X = CH2, R = R = H) to 1 99 (X = CO,... 

Mechanistic studies were performed for simple systems such as 1-thiabutadiene and ethylene481, although dimerization and cycloaddition of thiochalcones have received more attention, including several calculations482-484. Nevertheless, more synthetic utility possesses the uses of Lewis acids as catalysts in hetero-Diels-Alder reactions (equation 142)485,486 involving 1-thiabutadienes. 

The first example of an enantioselective thiadiene cycloaddition involved the reaction of 2,-4-diphenyl- 1-thiabuta-1,3-diene with l-propenoyl-l,3-oxazolidin-2-one. Stoichiometric quantities of a copper triflate bis-imine complex catalyst 428 and 4 A molecular sieves are necessary to achieve the highest enantioselectivity and the best endojexo ratio. The absolute configuration of the major endo isomer was determined by reduction of the acyloxazolidine side chain to the known (3/ ,4/ )-5-hydroxymethyl derivative (Scheme 137) <1997J(P1)2957>. The process is improved using a homochiral Cu triflate or Ni perchlorate bis(oxazoline) complex when catalytic amounts are adequate for a range of thiabutadienes <1999CC1001>. 

Incorporation of the thiabutadiene moiety into a camphor framework resulted in the reaction with various dienophiles proceeding with complete Jt-facial selectivity and, in some instances, exo-selectivity. The stereochemistry of one product was confirmed by X-ray analysis. The (arylmethylene)thiocamphor compounds 429 were prepared by thionation of the corresponding ketones with Lawesson s reagent and exist as stable monomers (Equation 125) <1999TL8383>. 

In an extension of the above hDA reaction, the cycloaddition of the thiabutadiene with maleic anhydride gives a 2-amido-277-thiopyran by way of elimination and addition of Me2NH to the anhydride unit (Equation 128) <2001M947>. 

When the isomeric thiabutadiene, iV-aryl-3-(2-thienyl)prop-2-enethioamide, reacts with diethyl fumarate in the presence of AcCl and pyridine, a 24 1 mixture of diastereomeric 3,4-dihydro-2//-thiopyrans 430 and 431 is formed (Equation 129) <2004M97>. 

The introduction of a bulky, optically active amino function at C-2 of 4-phenyl-l-thiabutadiene and activation by the addition of AcCl prior to cycloaddition with Wphenylmaleimide, known to exhibit a high endo preference, results in the formation of two diastereomers. However, the exo product is the major component and indeed this diastereo-mer is the sole adduct when cyclopentene is used as the dienophile. Calculations point to a preference for exo addition from the same face of the molecule as the naphthyl moiety and this is supported by the observed R stereochemistry at the three chiral centers in the cyclopenta[A]dihydrothiopyran 434 (Scheme 140) <1996TL123>. 

In the same field Guingant and Pradere have developed an asymmetric cycloaddition of 3-aza-l-thiabutadienes. The chiral auxiliary was brought here by the dienophile which is an unsaturated Evans amide [232]. It is remarkable that both enantiomers were selectively obtained by proper choice of the conditions catalysis of MgBr2 at 0°C or a pressure of 10 kbar at 20 °C (Table 4, entry 8). 

In contrast to the thorough studies of the Diels-Alder reactions of oxa- and aza-butadienes, the [4 + 2] cycloaddition reactions of 1-thia-1,3-butadienes have not been studied extensively.Although the general participation of thiabutadienes in LUMOdiene-controlled [4 + 2] cycloaddition reactions has been recognized and experimentally verified, most investigations have detailed their 4rr participation in HOMOdiene-controlled reactions with typical electron-deficient dienophiles. In such instances, the complementary C-2 or C-4 addition of electron-donating substituents to the 1-thia-1,3-butadiene increases the rate and regioselectivity of its Ait participation in HOMOdiene-controlled Diels-Alder reactions. With notable exceptions, the LUMOdiene-controlled Diels-Alder reactions provide the expected 2-substituted 3,4-dihydro-2//-thiopyrans and, unlike simple 1-oxa-1,3-butadienes, the HOMOdiene-controlled Diels-... 

Alder reactions of 1-thia-1,3-butadienes with electron-deficient or conjugated dienophiles provide 3-sub-stituted 3,4-dihydro-2ff-thiopyrans (equation 6). Representative Diels-Alder reactions of 1-thia-1,3-butadienes are presented in Table 7 and hetero-l-thiabutadienes that have been demonstrated to participate in [4 + 2] cycloaddition reactions are summarized in Figure 4. ... 

Asymmetric Diels-Alder reaction of 2-azadienes with acrylates using Cu(OTf)2 as a Lewis acid has been reported (Sch. 53) [99]. The reaction gives the exo product (244) with high enantioselectivity. Copper Lewis acid-mediated Diels-Alder reactions of thiabutadienes with oxazolidinone acrylate 196 have also been reported [100]. 

The chiral Ni(II) complex shown in Sch. 58 catalyzes the enantioselective hetero-Diels-Alder reactions of thiabutadienes with 3-(2-propenoyl)-2-oxazolidinone to afford optically active dihydrothiopyrans [204]. Similar results are obtained with analogous Cu(II) complexes where catalyst loading can be reduced when molecular sieves are added. 

The first catalytic, highly enantio selective hetero Diels-Alder reactions of thiabutadienes with an acyloxazolidinone dienophile using homochiral copper and nickel triflate and perchlorate bis(oxazoline) and bis(imine)complex catalysts to generate dihydrothiopyrans were reported by Saito et al. [155]. 

Saito, T, Takekawa, K, Takahashi, T, The first catalytic, highly enantioselective hetero-Diels-Alder reaction of thiabutadienes, Chem. Commun., 1001-1002, 1999. 

Chapter 9, Section 1), azodicarboxylates and related acyl and aroyl azo compounds (37, 2,3-diaza-l-oxabutadiene, Chapter 9, Section 5), acy-lsulfines (38) and -sulfenes (39,4-oxa-l-thiabutadiene, Chapter 8, Section 5), yV-sulfinylurethanes (40), and N-sulfonylamides and -urethanes (41, 2-aza-4-oxa-l-thiabutadiene, Chapter 9, Section 3). Chapters 8 and 9 detail the investigations on each of the systems indicated and should be consulted for citations and full discussions of their 4ir participation in Diels-Alder reactions. 

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