Double bonds diastereoselective synthesis

Lewis acids, results in the formation of isopulegol (43) with greater than 98% diastereoselectivity isopulegol (43), wherein all of the ring substituents are equatorially oriented, arises naturally from a chairlike transition state structure in which the C-3 methyl group, the coordinated C-l aldehyde carbonyl, and the A6,7 double bond are all equatorial (see 48). A low-temperature crystallization raises the chemical and enantiomeric purity of isopulegol (43) close to 100%. Finally, hydrogenation of the double bond in 43 completes the synthesis of (-)-menthol (1). 

The conversion of a thiolactone to a cyclic ether can also be used as a key step in the synthesis of functionalized, stereochemically complex oxacycles (see 64—>66, Scheme 13). Nucleophilic addition of the indicated higher order cuprate reagent to the C-S double bond in thiolactone 64 furnishes a tetrahedral thiolate ion which undergoes smooth conversion to didehydrooxepane 65 upon treatment with 1,4-diiodobutane and the non-nucleophilic base 1,2,2,6,6-pentamethylpiperidine (pempidine).27 Regio- and diastereoselective hydroboration of 65 then gives alcohol 66 in 89 % yield after oxidative workup. Versatile vinylstannanes can also be accessed from thiolactones.28 For example, treatment of bis(thiolactone) 67 with... 

For a successful application in synthesis, several problems have to be solved regioselectivity, whether the C-C bond is formed with the 1- or 3-position in an unsymmetrical ambident anion, EjZ selectivity in the formation of the double bond, and simple diastereoselectivity, since two new stereogenic centers are created from prostereogenic compounds. Further, different types of induced stereoselectivity or enantioselectivity may be required. Allylmetals with a wide choice of substituents are accessible by various methods (Sections D. 1.3.3.3.1.-10.). 

The reactions of allylboronates 1 (R = H or CH3) may proceed either by way of transition state 3, in which the a-substituent X adopts an axial position, or 4 in which X occupies an equatorial position. These two pathways are easily distinguished since 3 provides 7 with a Z-olefin, whereas 4 provides 8 with an E-olefinic linkage. There is also a second fundamental stereochemical difference between these two transition states 7 and 8 are heterochirally related from reactions in which 1 is not racemic. That is, 7 and 8 arc enantiomers once the stereochemistry-associated with the double bond is destroyed. Thus, the selectivity for reaction by way of 3 in preference to 4, or via 6 in preference to 5 in reactions of a-subsliluted (Z)-2-butenylboronate 2, is an important factor that determines the suitability of these reagents for applications in enantioselective or acyclic diastereoselective synthesis. 

Oxidation of cyclic phosphonoformaldehyde dithioacetal, using the Modena protocol, yields the trans disulfoxide 121 in excellent enantiomeric excess. Then 121, via HWE olefination and oxidation of the double bond has been used for the diastereoselective preparation of spirocyclic his-sulfinyl oxiranes (new versatile intermediates in asymmetric synthesis) [79] (Scheme 37). 

Pyrrolo[l,2- ][l,2]oxazines are a class of compounds with very few references regarding synthesis and reactivity. An interesting preparation has been described by intramolecular cyclization of IV-hydroxy pyrrolidines carrying a methoxyallene substituent at C-2 (242, Scheme 32). These compounds were obtained by addition of a lithiated allene to chiral cyclic nitrones 241. Cyclization occurred spontaneously after some days at relatively high dilution (0.05 M). Compounds 243 (obtained with excellent diastereoselectivity) can be submitted to further elaboration of the double bond or to hydrogenolysis of the N-O bond to form chiral pyrrolidine derivatives (Section 11.11.6.1) <2003EJ01153>. 

An important example of heterogeneous diastereoselective synthesis by catalytic way is the synthesis of prostaglandines (a family of compounds having the 20-carbon skeleton of the prostanoic acid) (Scheme 14.14). Naturally, these molecules are biosynthesized via a cyclooxygenase enzyme system that is widely distributed in mammalian tissues. Many of the synthetic routes [272] involve the diastereoselective hydrogenation of a carbonylic bond having a C=C double bond... 

The first diastereoselective total synthesis of ( )-guanacastepene A (rac-187) was published in a series of papers by Danishefsky and co-workers [107-110]. The tricyclic carbon framework was assembled by interplay of enolate alkylations and ring-closing carbon/carbon double bond forming reactions (Fig. 19). Commercially available cyclopentenone 90 was utilized as the A-ring precursor. 

Urea 32, the bis-(mono-trifluoromethyl)phenyl derivative of urea catalyst 16 [178], was reported to operate as double hydrogen-bonding organocatalyst in the diastereoselective synthesis of y-butenolide products substituted at the y-position... 

A striking example of the power of A -heterocyclic carbene (NHC)-bearing catalysts with sterically demanding substrates was disclosed by Chavez and Jacobsen, " who presented a route to several iridoid natural products, exemplified by the enantio- and diastereoselective synthesis of boschnialactone 31 outlined in Scheme 5. Chiral aldehyde 27, available from citronellal by Eschenmoser-methylenation in a single step, reacted despite the presence of an isoprenyl moiety and a gi OT-disubstituted double bond, in the presence of catalyst C smoothly to form... 

When dienones such as 55 are subjected to the epoxidation conditions the electron-poorer C=C double bond is selectively epoxidized. The other C=C bond can be functionalized further, for example, it can be dihydroxylated, as shown in the synthesis of the lactone 56 (Scheme 10.11) [82]. Stannyl epoxides such as 57 (Scheme 10.11, see also Table 10.8, R1 = n-Bu3Sn) can be coupled with several electrophiles [72], reduction of chalcone epoxide 58 and ring opening with alkyl aluminum compounds provides access to, e.g., the diol 59 and to phenylpropionic acids (for example 60). Tertiary epoxy alcohols such as 61 can be obtained with excellent diastereoselectivity by addition of Grignard reagents to epoxy ketones [88, 89]. 

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