Dispiroketal

Oxacyclopentylidene, 234 Butane-2,3-bisacetal, 235 Cyclohexane-1,2-diacetal, 235 Dispiroketals, 236... 

PhCH(OCH2CH2CH=CH2)2, CSA, NBS. Standard methods failed because of cleavage of the dispiroketal (dispoke) protective group. 

The 2,2 -bis(phenylthiomethyl) dispiroketal (dispoke) derivative is cleaved by oxidation to the sulfone, followed by treatment with LiN(TMS)2. The related bromo and iodo derivatives are cleaved reductively with LDBB (lithium 4,4 -di- -butylbiphenylide) or by elimination with the P4- -butylphosphazene base and acid hydrolysis of the enol ether. The 2,2-diphenyl dispiroketal is cleaved with FeCl3 (CH2CI2, rt, overnight)." The dimethyl dispiroketal is cleaved with TFA, and the allyl derivative is cleaved by ozonolysis followed by elimination. ... 

In 1991, an important paper was published by Bock et a/.84 that described the steric and electronic effects on the formation of the dispiroketal dihexulose dianhydrides. The authors described the conformation of six dihexulose dianhydrides, as determined by X-ray crystallography or NMR spectroscopy. They concluded that these conformations are dictated by the anomeric and exo-anomeric effects. Thus, the dihexulose dianhydrides are disposed to adopt conformations that permit operation of these effects—even if this results in the dioxane ring having a boat conformation or all three substituents on one pyranose ring being axial. 

The preparation of oxygen substituted porphyrazines as analogues to the thiol appended porphyrazines proved to be a formidable challenge. Unlike the sulfur appended porphyrazines for which Na2(mnt) was a readily available precursor, no simple dinitrile precursor could be prepared for the analogous oxygen systems. In 1997, this hurdle was overcome through the preparation of a chiral dispiroketal appended pz (11), which could be further deprotected to form the diol and then either peripherally metalated or converted to the pyridazine (10). These oxygen appended porphyrazines are described in Section VI. 

Structural Analysis. H2[pz(A4)] A = dispiroketal (190) has been structurally characterized, Fig. 40, and is shown to exhibit a noncrystallographic D2 symmetry the central core is planar to within 0.08 A. The presence of hydrogen atoms on the nitrogen centers distorts the potential D4 symmetry of the non-hydrogen atoms The transannular porphyrin N—N distances differ by-0.15 A (11). 

Additional unsymmetrical porphyrazinols have also been reported. The mixed macrocyclization of the dispiroketal substituted dinitrile (188) with di-terf-butyl phenyl pyrroline (68) gives Mg[pz(AB3)], A = dispiroketal, B = di-terf-butyl phenyl (194) in 30% yield, which can be demetalated with glacial acetic acid to... 

To prepare the trans and cis dispiroketal functionalized porphyrazines, the trans director, B = 4,7-bis(isopropyloxy) fused benzo, dintirile (1) was employed (13). Cyclization of dispiromaleonitrile (188) with a five-fold excess of (1) gave predominantly the trans pz, /ra .v-Mg pz(A2B2), A = dispiroketal, B = 4,7-bis(iso-propyloxy) fused benzo (199, 42%) and a small amount of the cis pz, cA-Mg[pz(A2B2), A = dispiroketal, B = 4,7-bis(isopropyloxy) fused benzo (200, 14%) (Scheme 39). 

Scheme 38. Preparation of unsymmetrical dispiroketal porphyrazines. [Adapted from (10).]...

As a second approach to stabilizing the pz-diols, bulky substituents at appropriate positions were employed to hinder electrophilic attack. The first synthesis of pz-diols was accomplished by removal of the dispiroketal protecting group from the centrally metalated porphyrazines, M[pz(AB3)], A = di-ferf-butyl phenyl, B = dipiroketal (197) (M = Ni) 198 (M = Cu) with acetic acid to form the stable, iso-lable porphyrazines, M [pz(AB3)], A = di-ferf-butyl phenyl, B = diol (203) (M = Ni) 204 (M = Cu) (Scheme 41) (10). 

Until recently, the protection of the trans-hydroxyl groups of sugars has been an inefficient process.2 This protection has now been simplified by the introduction of the dispiroketal protecting group,3 and the cyclohexane diacetal (CDA) protecting group.4... 

Some additional examples, where the stereochemical outcome of the cycloaddition to chiral alkenes has been explained in terms of the Honk—Jager model, should also be mentioned. The diastereomer ratio found in the reaction of y-oxy-a,p-unsamrated sulfones (166), with Morita-Baylis-Hillman adducts [i.e., ot-(a -hydro-xyalkyl)-acrylates (167)] (Scheme 6.27), with dispiroketal-protected 3-butene-l,2-diol (168), and with a,p-unsamrated carbonyl sugar and sugar nitroolefin (169) derivatives, all agree well with this model. 

Disubstituted dihydropyrans are produced with high u/iri-selectivity when 2-phenyl-4-(4-tolylsulfonyl)-3,4-dihydro-2H -pyrans ate treated with Al-based Lewis acids <99SL132>. Tetraenes 10, derived from dienes via their epoxides, undergo a double RCM reaction under Ru-catalysis to yield polycyclic ethers 11 in which the dihydropyran units can be joined by a variable number of carbon atoms <99JOC3354>. Continued work on the use of dispiroketals in synthesis has led to an improved route to the enantiomers of bi(dihydropyrans) 12 <99JCS(P1)1639>. 

Benzylidene and isopropylidene acetals of irons-1,2-diols are very labile as a result of ring strain and are not often used for synthetic applications. Fortunately, the protection of these diols can be accomplished with the recently developed dispiroketal (dispoke)35 and cyclohexane-1,2-diacetal (CDA) groups.36... 

Disodium hydrogen phosphate Phosphoric acid, disodium salt (7558-79-4), 76, 78 Dispiroketal (dispoke), 77, 215... 

Ley and coworkers have found that dispiroketals383, such as 1,8,13,16-tetrahydro-oxadispiro[5.0.5.4] hexadecanes, show a wide range of synthetic applications554. For the preparation of these compounds, 2-(tri-n-butylstannyl)dihydropyrans can be used554-556. The reaction of 2-lithio-6-methyl-2-(phenylsulfanyl)tetrahydropyran (375) with tri-n-butylstannyl chloride gave compound 381, which has further been transformed into the dispiroketal 382 (Scheme 100)555. 

Nakamura, S., Inagaki, J., Kudo, M., Sugimoto, T, Ohara, K., Nakajima, M. and Hashimoto, S., 2002. Studies directed toward the total synthesis of pinnatoxin A synthesis of the 6,5,6-dispiroketal (BCD ring) system by double hemiketal formation/hetero-Michael addition strategy. Tetrahedron 58, 10353-10374. 

Boons G-J, Grice P, Leslie R, Ley SV, Yeung LL. Dispiroketals in synthesis 5. A new opportunity for oligosaccharide synthesis using differentially activated glycosyl donors and acceptors. Tetrahedron Lett. 1993 34 8523-8526. 

---