A-Alkoxy lithiums

Addition reactions of various a-alkoxy lithium and a-alkoxy magnesium compounds 13, formed via the corresponding tributylstannanes, have been performed8. In every case the... 

A convenient route to highly enantiomerically enriched a-alkoxy tributylslannanes 17 involves the enanlioselective reduction of acyl stannanes 16 with chiral reducing agents10. Thus reaction of acyl stannanes with lithium aluminum hydride, chirally modified by (S)-l,l -bi-naphthalene-2,2 -diol, followed by protection of the hydroxy group, lead to the desired a-alkoxy stannanes 17 in optical purities as high as 98 % ee. 

Tin/lithium exchange on the a-alkoxy stannanes and subsequent addition of carbon dioxide led to optically active (7-protected a-hydroxy acids 18 with retention of configuration and without any loss of stereochemical information11. 

The a-alkoxy iron-acyl complex 5 may be deprotonated to generate the lithium enolate 6, which undergoes a highly diastereoselective aldol reaction with acetone to generate the adduct 7 as the major product. Deprotonation of acetone by 6 is believed to be a competing reaction 30% of the starting complex 5 is found in the product mixture48 40. 

The lithium enolate of a-alkoxy substituted complex 9 also exhibited little selectivity upon reaction with aldehydes all four possible diastereomers were produced when it was treated with acetaldehyde49. 

The lithium enolates of a-alkoxy esters exhibit high stereoselectivity, which is consistent with involvement of a chelated enolate.374 39 The chelated ester enolate is approached by the aldehyde in such a manner that the aldehyde R group avoids being between the a-alkoxy and methyl groups in the ester enolate. A syn product is favored for most ester groups, but this shifts to anti with extremely bulky groups. 

The potential for coordination depends on the oxy substituents.82 Alkoxy substituents are usually chelated, whereas highly hindered silyloxy groups usually do not chelate. Trimethylsiloxy groups are intermediate in chelating ability. The extent of chelation also depends on the Lewis acid. Studies with a-alkoxy and (3-alkoxy aldehydes with lithium enolates found only modest diastereoselectivity.83... 

In the presence of zinc chloride, stereoselective aldol reactions can be carried out. The aldol reaction with the lithium enolate of /-butyl malonate and various a-alkoxy aldehydes gave anti-l,2-diols in high yields, and 2-trityloxypropanal yielded the syn-l,2-diol under the same conditions.633 Stoichiometric amounts of zinc chloride contribute to the formation of aminoni-tropyridines by direct amination of nitropyridines with methoxyamine under basic conditions.634 Zinc chloride can also be used as a radical initiator.635... 

Alkynylzinc bromides, BrZnC=CR.6 Unlike magnesium and lithium ace-tylides, these reagents add to an a-alkoxy aldehyde with good to high syn-selectivity. Example ... 

Diastereoface selection has been investigated in the addition of enolates to a-alkoxy aldehydes (93). In the absence of chelation phenomena, transition states A and B (Scheme 19), with the OR substituent aligned perpendicular to the carbonyl a plane (Rl = OR), are considered (Oc-or c-r transition state R2 Nu steric parameters dictate that predoniinant diastereoface selection from A will occur. In the presence of strongly chelating metals, the cyclic transition states C and D can be invoked (85), and the same R2 Nu control element predicts the opposite diastereoface selection via transition state D (98). The aldol diastereoface selection that has been observed for aldehydes 111 and 112 with lithium enolates 99, 100, and 101 (eqs. [81-84]) (93) can generally be rationalized by a consideration of the Felkin transition states A and B (88) illustrated in Scheme 19, where A is preferred on steric grounds. 

On the contrary, a-lithiated epoxides have found wide application in syntheses . The existence of this type of intermediate as well as its carbenoid character became obvious from a transannular reaction of cyclooctene oxide 89 observed by Cope and coworkers. Thus, deuterium-labeling studies revealed that the lithiated epoxide 90 is formed upon treatment of the oxirane 89 with bases like lithium diethylamide. Then, a transannular C—H insertion occurs and the bicyclic carbinol 92 forms after protonation (equation 51). This result can be interpreted as a C—H insertion reaction of the lithium carbenoid 90 itself. On the other hand, this transformation could proceed via the a-alkoxy carbene 91. In both cases, the release of strain due to the opening of the oxirane ring is a significant driving force of the reaction. 

The lithium enolates of a-alkoxy esters have been extensively explored, and several cases in which high stereoselectivity is observed have been documented.14 This stereoselectivity can be explained in terms of a chelated ester enolate which is approached by the... 

Grignard reagents show some stereoselectivity in reactions with a-alkoxy aldehydes (threolerythreo = 10 1), but only slight stereoselectivity obtains in reactions with /J-alkoxy aldehydes. On the other hand, fairly high stereoselectivity is observed in the reaction of lithium dialkylcuprates with /5-alkoxy aldehydes, and again formation of the //ireo-product is favored (equation III). s... 

Comparable secondary a-alkoxy organolithiums were made from stannanes 313 and 314 and cyclised to tetrahydrofurans during a study of the stereospecificity of the cyclisation reaction with regard to the lithium-bearing centre.153 The stereochemical aspects of these reactions are discussed below. 

Novel nonchelation phenomena are observed with a steroidal a-hydroxy aldehyde. The reaction of a lithium or magnesium alkynide with the aldehyde gives the (20/, 22/ )-diastereomer piedominantiy, the formation of which was explained by Cram s cyclic model. When BF3-OEt2 is added to the lidiium alkynide prior to the addition of the aldehyde, the stereoselectivity is inverted, and the (20) ,225)-isomer is obtained as the principal product. Transformation of a-alkoxy aldehyde to the boron ate complex is suggested. Other l wis acids, such as B(OMe)3, AlCh, etc., are less effective (equation 29). °... 

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